Depression
Depression - Summary
Depression refers to a range of mental conditions characterized by persistent low mood, absence of positive affect, and a range of associated emotional, cognitive, physical, and behavioural symptoms. Symptoms occur on a continuum of severity, and day to day functioning is often impaired.
Depression is the third most common reason for consultation in general practice in the UK and is the most common psychiatric disorder. Each year, 6% of adults experience an episode of depression, and over the course of their lifetime more than 15% of the population will experience an episode.
The cause of depression is unknown but is likely to result from a complex interaction of biological, psychological, and social factors. Chronic comorbidities such as diabetes, chronic obstructive pulmonary disease, and cardiovascular disease make depression more likely. People with chronic pain are particularly likely to become depressed.
Depression is a major cause of impaired quality of life, reduced productivity, and increased mortality.
The average length of a depressive episode is 6–8 months. Recurrence is common:
At least 50% of all people affected by a first episode go on to have at least one more episode; after a second episode, the risk of a further recurrence increases to 70%; and after a third episode, to 90%.
Depression is diagnosed according to the ICD-10 classification. This requires the presence of one or more key symptoms for most of the time for at least two weeks, plus other symptoms associated with depression. The number of symptoms and degree of functional impairment indicate the severity of depression.
The risk of suicide should be assessed at initial presentation and regularly throughout treatment.
For people with mild-to-moderate depression, low-intensity psychological interventions (such as individual guided self-help, computerized cognitive behavioural therapy (CBT) or a structured group-based physical activity programme) are recommended.
Antidepressants are not used routinely for mild-to-moderate depression, but may be used for people with a history of depression, persistent subthreshold symptoms, or a concomitant chronic physical health problem.
For people with moderate or severe depression, a combination of an antidepressant and a high-intensity psychological intervention (such as CBT or interpersonal therapy) is recommended.
For a first episode of depression, a generic selective serotonin reuptake inhibitor such as citalopram, fluoxetine, paroxetine, or sertraline is recommended.
For a recurrent episode, an antidepressant that has previously elicited a good response may be more appropriate.
Frequent, regular review (every 2-4 weeks) is essential for all people with depression. At review the person should be assessed for:
Suicide risk.
Response to treatment.
Adherence to treatment and adverse effects.
Antidepressants should be continued for at least 6 months following remission of symptoms, as this greatly reduces the risk of relapse.
Have I got the right topic?
This CKS topic is based on guidelines published by the National Institute for Health and Clinical Excellence (NICE) — Depression: the treatment and management of depression in adults (CG90) [National Collaborating Centre for Mental Health, 2009a] and Depression in adults with a chronic physical health problem (CG91) [National Collaborating Centre for Mental Health, 2009b].
This CKS topic covers the assessment and management of adults with depression in primary care.
This CKS topic does not cover the management of pregnant or breastfeeding women with depression, or people with other primary psychiatric disorders such as schizophrenia.
There are separate CKS topics on Bipolar disorder, Depression - antenatal and postnatal, Poisoning or overdose, and Schizophrenia.
The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary health care.
How up-to-date is this topic?
How up-to-date is this topic?
Changes
February 2013 — minor update. The 2013 QIPP options for local implementation have been added to this topic [NICE, 2013].
October 2012 — minor update. The 2012 QIPP options for local implementation have been added to this topic [NPC, 2012].
March 2012 — minor update. The 2012/2013 QOF indicators have been added to this topic [BMA and NHS Employers, 2012]. Issued in April 2012.
January 2012 — minor update. References to the Quality and outcomes framework guidance for GMS contract 2011/12 updated throughout the topic [BMA and NHS Employers, 2011b]. Issued in February 2012.
January 2012 — minor update. Added updated information from the manufacturer's Summary of Product Characteristics (SPC) that venlafaxine may alter glycaemic control [ABPI Medicines Compendium, 2011b]. Issued January 2012.
January 2012 — minor update. Lundbeck Ltd, in collaboration with the Medicines and Healthcare products Regulatory Agency (MHRA), has published new safety data regarding the association of citalopram and escitalopram with dose-dependent QT interval prolongation [Lundbeck Ltd, 2011a; Lundbeck Ltd, 2011b; MHRA, 2011]. This topic has been updated to reflect their advice including new maximum doses, adverse effects, and drug interactions. Issued in January 2012.
May 2011 — minor update. The 2011/2012 QOF indicators have been added to this topic [BMA and NHS Employers, 2011a]. Issued in June 2011.
May 2011 — interaction between SSRIs and tamoxifen added as stated in the most recent SPCs [ABPI Medicines Compendium, 2011a; ABPI Medicines Compendium, 2011a]. Issued in June 2011.
March 2011 — minor update. The NICE quality standards on the management of depression have been added. Issued in June 2011.
December 2010 — minor update. Expert opinion from UK Medicines Information (UKMI) [UKMI, 2010] on the choice of antidepressant in people with epilepsy has been added to the Prescribing information section on Chronic physical health problems. Issued in December 2010.
October 2010 — minor update. Information on fitness to drive from the Driver and Vehicle Licensing Agency's guidance for medical practitioners, At a glance guide to the current medical standards of fitness to drive has been added [DVLA, 2010]. Issued in October 2010.
June 2010 — minor update. The Medicines and Healthcare products Regulatory Agency (MHRA) has advised that epidemiological data show that SSRIs and TCAs are associated with a small increased risk of fractures. However, the mechanism leading to this increased risk is unclear [MHRA, 2010]. Issued in June 2010.
March 2010 — minor update to correct a typographical error in the prescribing information text. Issued in March 2010.
August 2009 to February 2010 — converted from CKS guidance to CKS topic structure. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence.
The new CKS topic includes:
Updated classification of depressive illness based on DSM-IV criteria.
Updated guidance to base diagnosis on severity, duration, and course of symptoms rather than a symptoms count alone.
Updated evaluations and recommendations for use of psychological interventions.
Updated general principles of care and the recommended timing of pharmaceutical and psychological interventions.
Previous changes
March 2009 — minor update. The Quality and Outcomes Framework (QOF) indicators for depression have been updated in the Goals and outcome measures section. Hypopituitarism following traumatic brain injury has also been included as an underlying cause of depression. Issued in April 2009.
September 2008 — minor correction to the Changes section. Issued in September 2008.
November 2007 — updated to include recommendations from NICE technology appraisal Computerised cognitive behavioural therapy for depression and anxiety.
June 2006 — updated to include amended NICE guidance regarding venlafaxine.
January 2006 — updated to include recent advice from the MHRA regarding the safety of paroxetine in pregnancy. Quality and outcomes framework indicators for depression included. Issued in February 2006.
May 2005 — rewritten. Validated in September 2005 and issued in November 2005.
April 2004 — updated to include recent advice from the Committee on Safety of Medicines that the recommended target dosage of paroxetine is 20 mg daily. Maintenance prescriptions for higher doses have been removed. Issued in July 2004.
November 2002 — updated to include the management of postnatal depression. Validated in March 2003 and issued in April 2003.
September 2001 — reviewed. Validated in November 2001 and issued in April 2002. This guidance will be rewritten when the National Institute for Health and Clinical Excellence (NICE) publishes its guidance on the primary care management of depression, which is anticipated in September 2003.
August 1998 — written, replacing the guidance Single major depressive episode and Recurrent major depressive episode.
Update
New evidence
NHS Evidence published an evidence update on depression in April 2012. [Free Full-text (pdf)]
NHS Evidence published an evidence update on depression in adults with a chronic physical health problem in March 2012. [Free Full-text (pdf)]
Evidence-based guidelines
Guidelines published since the last revision of this topic:
American Psychiatric Association (2010) Practice guideline for the treatment of patients with major depressive disorder. 3rd edn. American Psychiatric Association. www.psych.org [Free Full-text]
NICE (2011) Generalised anxiety disorder and panic disorder (with or without agoraphobia) in adults. Management in primary, secondary and community care. NICE clinical guideline 113. National Institute for Health and Clinical Excellence. www.nice.org.uk [Free full-text]
SIGN (2010) Non-pharmaceutical management of depression. Scottish Intercollegiate Guidelines Network. www.sign.ac.uk [Free Full-text]
US Preventive Services Task Force (2009) Clinical guidelines: screening for depression in adults: US Preventive Services Task Force recommendation statement. Annals of Internal Medicine 151(11), 784-792. [Abstract] [Free Full-text]
HTAs (Health Technology Assessments)
No new HTAs since 1 November 2009.
Economic appraisals
No new economic appraisals relevant to England since 1 November 2009.
Systematic reviews and meta-analyses
Systematic reviews published since the last revision of the topic:
Ali, M.K., and Lam, R.W. (2011) Comparative efficacy of escitalopram in the treatment of major depressive disorder. Neuropsychiatric Disease and Treatment 7, 39-49. [Abstract] [Free Full-text]
Andrews, G., Cuijpers, P., Craske, M.G., et al. (2010) Computer therapy for the anxiety and depressive disorders is effective, acceptable and practical health care: a meta-analysis. PLoS One 5(10), e13196. [Abstract] [Free Full-text]
Anglin, R.E., Samaan, Z., Walter, S.D., and McDonald, S.D. (2013) Vitamin D deficiency and depression in adults: systematic review and meta-analysis. British Journal of Psychiatry 202(2), 100-107. [Abstract]
Archer, J., Bower, P., Gilbody, S., et al. (2012) Collaborative care for depression and anxiety problems (Cochrane Review). The Cochrane Library. Issue 10. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Barbui, C. Cipriani, A., Patel, V., et al. (2011) Efficacy of antidepressants and benzodiazepines in minor depression: systematic review and meta-analysis. British Journal of Psychiatry 198(1), 11-16. [Abstract] [Free Full-text]
Baumeister, H., Hutter, N., and Bengel, J. (2012) Psychological and pharmacological interventions for depression in patients with diabetes mellitus and depression (Cochrane Review). The Cochrane Library. Issue 12. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Beltman, M.W., Voshaar, R.C., and Speckens, A.E. (2010) Cognitive-behavioural therapy for depression in people with a somatic disease: meta-analysis of randomised controlled trials. British Journal of Psychiatry 197(1), 11-19. [Abstract] [Free Full-text]
Bloch, M.H. and Hannestad, J. (2012) Omega-3 fatty acids for the treatment of depression: systematic review and meta-analysis. Molecular Psychiatry 17(12), 1272-1282. [Abstract]
Bower, P., Kontopantelis, E., Sutton, A., et al. (2013) Influence of initial severity of depression on effectiveness of low intensity interventions: meta-analysis of individual patient data. BMJ 346, f540. [Abstract] [Free Full-text]
Bridle, C., Spanjers, K., Patel, S., et al. (2012) Effect of exercise on depression severity in older people: systematic review and meta-analysis of randomised controlled trials. British Journal of Psychiatry 201(3), 180-185. [Abstract]
Brunton, S., Wang, F., Edwards, S.B., et al (2010) Profile of adverse events with duloxetine: a pooled analysis of placebo-controlled studies. Drug Safety 33(5), 393-407. [Abstract]
Cabello, M., Mellor-Marsa, B., Sabariego, C., et al. (2012) Psychosocial features of depression: a systematic literature review. Journal of Affective Disorders 141(1), 22-33. [Abstract]
Cameron, I.M., Cardy, A., Crawford, J.R., et al. (2011) Measuring depression severity in general practice: discriminatory performance of PHQ-9, HADS-D, and BDI-II. BJGP 61(588), 454-457. [Abstract] [Free Full-text]
Cape, J., Whittington, C., Buszewicz, M., et al. (2010) Brief psychological therapies for anxiety and depression in primary care: meta-analysis and meta-regression. BMC Medicine 8, 38. [Abstract] [Free Full-text]
Cipriani, A., Koesters, M., Furukawa, T.A., et al. (2012) Duloxetine versus other anti-depressive agents for depression (Cochrane Review). The Cochrane Library. Issue 10. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Capriani, A., La Ferla, T., Furukawa, T.A., et al. (2010) Sertraline versus other antidepressive agents for depression (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Cipriani, A., Purgato, M., Furukawa, T.A., et al. (2012) Citalopram versus other anti-depressive agents for depression (Cochrane Review). The Cochrane Library. Issue 7. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Chan, M.F., Wong, Z.Y. and Thayala, N.V. (2011) The effectiveness of music listening in reducing depressive symptoms in adults: a systematic review. Complementary and Therapies in Medicine 19(6), 332-348. [Abstract]
Chen, J., Gao, K., and Kemp, D.E. (2010) Second-generation antipsychotics in major depressive disorder? Update and clinical perspective. Current Opinion in Psychiatry 24(1), 10-17. [Abstract]
Chi, I., Jordan-Marsh, M., Guo, M., et al. (2013) Tai chi and reduction of depressive symptoms for older adults: a meta-analysis of randomized trials. Geriatrics and Gerontology International 13(1), 3-12. [Abstract]
Chong, W.W., Aslani, P., and Chen, T.F. (2011) Effectiveness of interventions to improve antidepressant medication adherence: a systematic review. International Journal of Clinical Practice 65(9), 954-975. [Abstract] [Free Full-text]
Coull, G. and Morris, P.G. (2011) The clinical effectiveness of CBT-based guided self-help interventions for anxiety and depressive disorders: a systematic review. Psychological Medicine 41(11), 2239-2252. [Abstract]
Cuijpers, P., Donker, T., Johansson, R., et al. (2011) Self-guided psychological treatment for depressive symptoms: a meta-analysis. PLoS One 6(6), e21274. [Abstract] [Free Full-text]
Cuijpers, P., van Straten, A., Bohlmeijer, E., et al. (2010) The effects of psychotherapy for adult depression are overestimated: a meta-analysis of study quality and effect size. Psychological Medicine 40(2), 211-223. [Abstract]
Cuijpers, P., van Straten, A., Schuurmans, J., et al. (2010) Psychotherapy for chronic major depression and dysthymia: a meta-analysis. Clinical Psychology Review 30(1), 51-62. [Abstract]
Cuijpers, P., Geraedts, A.S., van Oppen, P., et al. (2011) Interpersonal psychotherapy for depression: a meta-analysis. American Journal of Psychiatry 168(6), 581-592. [Abstract]
Derom, M.L., Sayon-Orea, C., Martinez-Ortega, J.M., and Martinez-Gonzalez, M.A. (2012) Magnesium and depression: a systematic review. Nutritional Neuroscience epub ahead of print. [Abstract]
de Silva, V.A. and Hanwella, R. (2012) Efficacy and tolerability of venlafaxine versus specific serotonin reuptake inhibitors in treatment of major depressive disorder: a meta-analysis of published studies. International Clinical Psychopharmacology 27(1), 8-16. [Abstract]
Dowlati, Y., Herrmann, N., Swardfager, W.L., et al. (2010) Efficacy and tolerability of antidepressants for treatment of depression in coronary artery disease: a meta-analysis. Canadian Journal of Psychiatry 55(2), 91-99. [Abstract]
Driessen, E., Cuijpers, P., de Maat, S.C., et al. (2010) The efficacy of short-term psychodynamic psychotherapy for depression: a meta-analysis. Clinical Psychology Review 30(1), 25-36. [Abstract]
Dubicka, B., Elvins, R., Roberts, C., et al. (2010) Combined treatment with cognitive-behavioural therapy in adolescent depression: meta-analysis. British Journal of Psychiatry 197(6), 433-440. [Abstract] [Free Full-text]
Duncan, E., Best, C. and Hagen, S. (2010) Shared decision making interventions for people with mental health conditions (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Dwyer, A.V., Whitten, D.L. and Hawrelak, J.A. (2011) Herbal medicines, other than St. John’s wort, in the treatment of depression: a systematic review. Alternative Medicine Review 16(1), 40-49. [Abstract] [Free Full-text (pdf)]
Eom, C.S., Lee, H.K., Ye, S., et al. (2012) Use of selective serotonin reuptake inhibitors and risk of fracture: a systematic review and meta-analysis. Journal of Bone and Mineral Research 27(5), 1186-1195. [Abstract]
Epp, A.M., Dobson, K.S., Dozois, D.J., and Frewen, P.A. (2012) A systematic meta-analysis of the Stroop task in depression. Clinical Psychology Review 32(4), 316-328. [Abstract]
Ernst, E., Lee, M.S., and Choi, T.Y. (2011) Acupuncture for depression? A systematic review of systematic reviews. Evaluation and the Health Professions 34(4), 403-412. [Abstract]
Eyding, D., Lelgemann, M., Grouven, U., et al. (2010) Reboxetine for acute treatment of major depression: systematic review and meta-analysis of published and unpublished placebo and selective serotonin reuptake inhibitor controlled trials. BMJ 341, c4737. [Abstract] [Free Full-text]
Forsman, A.K., Schierenbeck, I. and Wahlbeck, K. (2011) Psychosocial interventions for the prevention of depression in older adults: systematic review and meta-analysis. Journal of Aging Health 23(3), 387-416. [Abstract]
Fournier, J.C., DeRubeis, R.J., Hollon, S.D., et al. (2009) Antidepressant drug effects and depression severity: a patient-level meta-analysis. Journal of the American Medical Association 303(1), 47-53. [Abstract] [Free Full-text]
Gao, Y., Huang, C., Zhao, K., et al. (2012) Depression as a risk factor for dementia and mild cognitive impairment: a meta-analysis of longitudinal studies. International Journal of Geriatric Psychiatry epub ahead of print. [Abstract]
Gibbons, R.D., Brown, H., Hur, K., et al. (2012) Suicidal thoughts and behavior with antidepressant treatment. Reanalysis of the randomized placebo-controlled studies of fluoxetine and venlafaxine. Archives of General Psychiatry 69(6), 580-587. [Abstract] [Free Full-text]
Gierisch, J.M., Bastian, L.A., Calhoun, P.S., et al. (2011) Smoking cessation interventions for patients with depression: a systematic review and meta-analysis. Journal of General Internal Medicine 27(3), 351-360. [Abstract]
Glue, P., Donovan, M.R., Kolluri, S., and Emir, B. (2010) Meta-analysis of relapse prevention antidepressant trials in depressive disorders. Australian & New Zealand Journal of Psychiatry 44(8), 697-705. [Abstract]
Gould, R.L., Coulson, M.C., and Howard, R.J. (2012) Cognitive behavioral therapy for depression in older people: a meta-analysis and meta-regression of randomized controlled trials. Journal of the American Geriatric Society 60(10), 1817-1830. [Abstract]
Gregory, V.L. (2010) Cognitive-behavioral therapy for depression in bipolar disorder: a meta-analysis. Journal of Evidence-based Social Work 7(4), 269-279. [Abstract]
Hawton, K., Casanas I Comabella, C., Haw, C., and Saunders, K. (2013) Risk factors for suicide in individuals with depression: a systematic review. Journal of Affective Disorders epub ahead of print. [Abstract]
Herring, M.P., Puetz, T.W., O'Connor, P.J. and Dishman, R.K. (2012) Effect of exercise training on depressive symptoms among patients with a chronic illness: a systematic review and meta-analysis of randomized controlled trials. Archives of Internal Medicine 172(2), 101-111. [Abstract]
Holzel, L., Harter, M., Reese, C., and Kriston, L. (2011) Risk factors for chronic depression - a systematic review. Journal of Affective Disorders 129(1-3), 1-13. [Abstract]
Hou, W.H., Chiang, P.T., Hsu, T.Y., et al. (2010) Treatment effects of massage therapy in depressed people: a meta-analysis. Journal of Clinical Psychiatry 71(7), 894-901. [Abstract]
Jackson, J.L., Shimeall, W., Sessums, L., et al. (2010) Tricyclic antidepressants and headaches: systematic review and meta-analysis. BMJ 341, c5222. [Abstract] [Free Full-text]
Jakobsen, J.C., Lindschou Hansen, J., Storebø, O.J., et al. (2011) The effects of cognitive therapy versus 'treatment as usual' in patients with major depressive disorder. PLoS One 6(8), e22890. [Abstract] [Free Full-text]
Josefsson, T., Lindwall, M., and Archer, T. (2013) Physical exercise intervention in depressive disorders: meta-analysis and systematic review. Scandinavian Journal of Medicine and Science in Sports epub ahead of print. [Abstract]
Khan, A., Faucett, J., Lichtenberg, P., et al. (2012) A systematic review of comparative efficacy of treatments and controls for depression. PLoS One 7(7), e41778. [Abstract] [Free Full-text]
Knorr, U., and Kessing, L.V. (2010) The effect of selective serotonin reuptake inhibitors in healthy subjects. A systematic review. Nordic Journal of Psychiatry 64(3), 153-163. [Abstract]
Knorr, U., Vinberg, M., Kessing, L.V., and Wetterslev, J. (2010) Salivary cortisol in depressed patients versus control persons: A systematic review and meta-analysis. Psychoneuroendocrinology 35(9), 1275-1286. [Abstract]
Kok, R.M., Heeren, T.J. and Nolen, W.A. (2011) Continuing treatment of depression in the elderly: a systematic review and meta-analysis of double-blinded randomized controlled trials with antidepressants. American Journal of Geriatric Psychiatry 19(3), 249-255. [Abstract]
Krishna, M., Jauhari, A., Lepping, P., et al. (2010) Is group psychotherapy effective in older adults with depression? A systematic review. International Journal of Geriatric Psychiatry 26(4), 331-340. [Abstract]
Krogh, J., Nordentoft, M., Sterne, J.A., and Lawlor, D.A. (2011) The effect of exercise in clinically depressed adults: systematic review and meta-analysis of randomized controlled trials. Journal of Clinical Psychiatry 72(4), 529-538. [Abstract]
Lai, J., Moxey, A., Nowak, G., et al. (2012) The efficacy of zinc supplementation in depression: systematic review of randomized controlled trials. Journal of Affective Disorders 136(1-2), e31-e39. [Abstract]
Lee, S.Y., Franchetti, M.K., Imanbayev, A., et al. (2012) Non-pharmacological prevention of major depression among community-dwelling older adults: a systematic review of the efficacy of psychotherapy interventions. Archives of Gerontology and Geriatrics 55(3), 522-529. [Abstract]
Leucht, C., Huhn, M., and Leucht, S. (2012) Amitriptyline versus placebo for major depressive disorder (Cochrane Review). The Cochrane Library. Issue 12. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Luppa, M., Sikorski, C., Luck, T., et al. (2012) Age- and gender-specific prevalence of depression in latest-life: systematic review and meta-analysis. Journal of Affective Disorders 136(3), 212-221. [Abstract]
Macedo, A., Leiria, E., and Filipe, A. (2010) Pirlindole in the treatment of depression: a meta-analysis. Clinical Drug Investigation 31(1), 61-71. [Abstract]
Maneeton, N., Maneeton, B., Srisurapanont, M., and Martin, S.D. (2012) Quetiapine monotherapy in acute phase for major depressive disorder: a meta-analysis of randomized, placebo-controlled trials. BMC Psychiatry 12, 160. [Abstract] [Free Full-text]
Meng, L., Chen,. D., Yang, Y., et al. (2012) Depression increases the risk of hypertension incidence: a meta-analysis of prospective cohort studies. Journal of Hypertension 30(5), 842-851. [Abstract]
Mitchell, A.J., Bird, V., Rizzo, M. and Meader, N. (2010) Which version of the geriatric depression scale is most useful in medical settings and nursing homes? Diagnostic validity meta-analysis. American Journal of Geriatric Psychiatry 18(12), 1066-1077. [Abstract]
Mitchell, A.J., Rao, S., and Vaze, A. (2010) Can general practitioners identify people with distress and mild depression? A meta-analysis of clinical accuracy. Journal of Affective Disorders 130(1-2), 26-36. [Abstract]
Morriss, R., Marttunnen, S., Garland, A., et al. (2010) Randomised controlled trial of the clinical and cost effectiveness of a specialist team for managing refractory unipolar depressive disorder. BMC Psychiatry 10, 100. [Abstract] [Free Full-text]
Nelson, J.C. and Devanand, D.P. (2011) A systematic review and meta-analysis of placebo-controlled antidepressant studies in people with depression and dementia. Journal of the American Geriatrics Society 59(4), 577-585. [Abstract]
Nieuwsma, J.A., Trivedi, R.B., McDuffie, J., et al. (2012) Brief psychotherapy for depression: a systematic review and meta-analysis. International Journal of Psychiatric Medicine 43(2), 129-151. [Abstract]
O'Connor, E.A., Whitlock, E.P., Beil, T.L. and Gaynes, B.N. (2009) Clinical guidelines: screening for depression in adult patients in primary care settings: a systematic evidence review. Annals of Internal Medicine 151(11), 793-803. [Abstract] [Free Full-text]
Oestergaard, S. and Moldrup, C. (2010) Optimal duration of combined psychotherapy and pharmacotherapy for patients with moderate and severe depression: a meta-analysis. Journal of Affective Disorders 131(1-3), 24-36. [Abstract]
Omori, I.M., Watanabe, N., Nakagawa, A., et al. (2010)Fluvoxamine versus other anti-depressive agents for depression (Cochrane Review). The Cochrane Library. Issue 3. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Papakostas, G.I., Charles, D., and Fava, M. (2010) Are typical starting doses of the selective serotonin reuptake inhibitors sub-optimal? A meta-analysis of randomized, double-blind, placebo-controlled, dose-finding studies in major depressive disorder. World Journal of Biological Psychiatry 11(2 Pt2), 300-307. [Abstract]
Pfeiffer, P.N., Heisler, M., Piette, J.D., et al. (2011) Efficacy of peer support interventions for depression: a meta-analysis. General Hospital Psychiatry 33(1), 29-36. [Abstract] [Free Full-text]
Piek, E., van der Meer, K. and Nolen, W.A. (2010) Guideline recommendations for long-term treatment of depression with antidepressants in primary care - a critical review. European Journal of General Practice 16(2), 106-112. [Abstract]
Rabenda, V., Nicolet, D., Beaudart, C., et al. (2013) Relationship between use of antidepressants and risk of fractures: a meta-analysis. Osteoporosis International 24(1), 121-137. [Abstract]
Ramsberg, J., Assesburg, C. and Henriksson, M. (2012) Effectiveness and cost-effectiveness of antidepressants in primary care: a multiple treatment comparison meta-analysis and cost-effectiveness model. PLoS One 7(8), e42003. [Abstract] [Free Full-text]
Rayner, L., Price, A., Evans, A., et al. (2010) Antidepressants for depression in physically ill people (Cochrane Review). The Cochrane Library. Issue 3. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Rocha, F.L., Fuzikawa, C., Riera, R., and Hara, C. (2012) Combination of antidepressants in the treatment of major depressive disorder: a systematic review and meta-analysis. Journal of Clinical Psychopharmacology 32(2), 278-281. [Abstract]
Rodgers, M., Asaria, M., Walker, S., et al. (2012) The clinical effectiveness and cost-effectiveness of low-intensity psychological interventions for the secondary prevention of relapse after depression: a systematic review. Health Technology Assessment 16(28), 1-130. [Abstract] [Free Full-text]
Rooney, A., and Grant, R. (2010) Pharmacological treatment of depression in patients with a primary brain tumour (Cochrane Review). The Cochrane Library. Issue 3. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Rubio-Valera, M., Serrano-Blanco, A., Magdalena-Belio, H., et al. (2011) Effectiveness of pharmacist care in the improvement of adherence to antidepressants: a systematic review and meta-analysis. Annals of Pharmacotherapy 45(1), 39-48. [Abstract]
Samad, Z., Brealey, S. and Gilbody, S. (2011) The effectiveness of behavioural therapy for the treatment of depression in older adults: a meta-analysis. International Journal of Geriatric Psychiatry 26(12), 1211-1220. [Abstract]
Seitz, D.P., Gill, S.S. and Conn, D.K. (2010) Citalopram versus other antidepressants for late-life depression: a systematic review and meta-analysis. International Journal of Geriatric Psychiatry 25(12), 1296-1305. [Abstract]
Sharp, J., Holly, D. and Broomfield, N. (2012) Computerized cognitive behaviour therapy for depression in people with a chronic physical illness. British Journal of Health Psychology epub ahead of print. [Abstract]
Silveira, H., Moraes, H., Oliveira, N., et al. (2013) Physical exercise and clinically depressed patients: a systematic review and meta-analysis. Neuropsychobiology 67(2), 61-68. [Abstract]
Singh, S.P., Singh, V., and Kar, N. (2011) Efficacy of agomelatine in major depressive disorder: meta-analysis and appraisal. International Journal of Neuropsychopharmacology epub ahead of print. [Abstract]
Smith, C.A., Hay, P.P.J. and MacPherson, H. (2010) Acupuncture for depression (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Soucy Chartier, I. and Provencher, M.D. (2013) Behavioural activation for depression: efficacy, effectiveness and dissemination. Journal of Affective Disorders 145(3), 292-299. [Abstract]
Spielmans, G.I., Berman, M.I. and Usitalo, A.N. (2011) Psychotherapy versus second-generation antidepressants in the treatment of depression: a meta-analysis. Journal of Nervous and Mental Disease 199(3), 142-149. [Abstract]
Taylor, D., Meader, N., Bird, V., et al. (2011) Pharmacological interventions for people with depression and chronic physic health problems: systematic review and meta-analyses of safety and efficacy. British Journal of Psychiatry 198(3), 179-188. [Abstract] [Free Full-text]
Tedeschini, E., Levkovitz, Y., Iovieno, N., et al. (2011) Efficacy of antidepressants for late-life depression: a meta-analysis and meta-regression of placebo-controlled randomized trials. Journal of Clinical Psychiatry 72(12), 1660-1668. [Abstract]
Thaler, K., Delivuk, M., Chapman, A., et al (2011) Second-generation antidepressants for seasonal affective disorder (Cochrane Review). The Cochrane Library. Issue 12. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Thaler, K., Morgan, L.C., van Noord, M., et al. (2012) Comparative effectiveness of second-generation antidepressants for accompanying anxiety, insomnia, and pain in depressed patients: a systematic review. Depression and Anxiety 29(6), 495-505. [Abstract]
Trkulja, V. (2010) Is escitalopram really relevantly superior to citalopram in treatment of major depressive disorder? A meta-analysis of head-to-head randomized trials. Croatian Medial Journal 51(1), 61-73. [Abstract] [Free Full-text]
Vázquez, G., Tondo, L. and Baldessarini, R.J. (2010) Comparison of antidepressant responses in patients with bipolar vs. unipolar depression: a meta-analytic review. Pharmacopsychiatry 44(1), 21-26. [Abstract]
van Marwijk, H., Allick, G., Wegman, F., et al. (2012) Alprazolam for depression (Cochrane Review). The Cochrane Library. Issue 7. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
van Wolff, A., Holzel, L.P., Westphal, A., et al. (2012) Combination of pharmacotherapy and psychotherapy in the treatment of chronic depression: a systematic review and meta-analysis. BMC Psychiatry 12, 61. [Abstract] [Free Full-text]
Wade, A.G. (2010) Use of the internet to assist in the treatment of depression and anxiety: a systematic review. Primary Care Companion to the Journal of Clinical Psychiatry12(4). [Abstract] [Free Full-text]
Watanabe, N., Omori, I.M., Nakagawa, A., et al. (2011) Mirtazapine versus other antidepressive agents for depression (Cochrane Review). The Cochrane Library. Issue 12. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Wilkinson, P. and Izmeth, Z. (2012) Continuation and maintenance treatments for depression in older people (Cochrane review). The Cochrane Library. Issue 11. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Wu, Q., Bencaz, A.F., Hentz, J.G., and Crowell, M.D. (2012) Selective serotonin reuptake inhibitor treatment and risk of fractures: a meta-analysis of cohort and case-control studies. Osteoporosis International 23(1), 365-367. [Abstract]
Yohannes, A.M. and Caton, S. (2010) Management of depression in older people with osteoarthritis: a systematic review. Aging and Mental Health 14(6), 637-651. [Abstract]
Zhao, K.X., Huang, C.Q., Xiao, Q., et al. (2012) Age and risk for depression among the elderly: a meta-analysis of the published literature. CNS Spectrums 17(3), 142-154. [Abstract]
Primary evidence
Randomized controlled trials published in the major journals since the last revision of this topic:
Chalder, M., Wiles, N., Campbell, J., et al. (2012) A pragmatic randomised controlled trial to evaluate the cost-effectiveness of a physical activity intervention as a treatment for depression: the treating depression with physical activity (TREAD) trial. Health Technology Assessment 16(10), 1-164. [Abstract] [Free Full-text]
Chalder, M., Wiles, N.J., Campbell, J., et al. (2012) Facilitated physical activity as a treatment for depressed adults: randomised controlled trial. BMJ 344, e2758. [Abstract] [Free Full-text]
Hellerstein, D.J., Stewart, J.W., McGrath, P.J., et al. (2012) A randomized controlled trial of duloxetine versus placebo in the treatment of nonmajor chronic depression. Journal of Clinical Psychiatry 73(7), 984-991. [Abstract]
Mohr, D.C., Ho, J., Duffecy, J., et al. (2012) Effect of telephone-administered vs face-to-face cognitive behavioural therapy on adherence to therapy and depression outcomes among primary care patients. A randomized trial. JAMA 307(21), 2278-2285. [Abstract]
Pettinati, H.M., Oslin, D.W., Kampman, K.M., et al. (2010) A double-blind, placebo-controlled trial combining sertraline and naltrexone for treating co-occurring depression and alcohol dependence. American Journal of Psychiatry 167(6), 668-675. [Abstract] [Free Full-text]
Serfaty, M.A., Haworth, D., Blanchard, M., et al. (2009) Clinical effectiveness of individual cognitive behavioral therapy for depressed older people in primary care: a randomized controlled trial. Archives of General Psychiatry 66(12), 1332-1340. [Abstract] [Free Full-text]
Wiles, N., Thomas, L., Abel, A., et al. (2012) Cognitive behavioural therapy as an adjunct to pharmacotherapy for primary care based patients with treatment resistant depression: results of the CoBalT randomised controlled trial. Lancet 381(9864), 375-384. [Abstract]
Reanalyses of randomised controlled trials have been published since the last revision of this topic:
Gibbons, R.D., Brown, H., Hur, K., et al. (2012) Suicidal thoughts and behaviour with antidepressant treatment. Reanalysis of the randomized placebo- controlled studies of fluoxetine and venlafaxine. Archives of General Psychiatry 69(6), 580-587. [Abstract] [Free Full-text]
Gibbons, R.D., Hur, K., Brown, H., et al. (2012) Benefits from antidepressants. Synthesis of 6-week patient-level outcomes from double-blind placebo-controlled randomized trials of fluoxetine and venlafaxine. Archives of General Psychiatry 69(6), 572-579. [Abstract] [Free Full-text]
Observational studies published since the last revision of this topic:
Baldessarini, R., Tondo, L, Ghiani, C. and Lepri, B. (2010) Illness risk following rapid versus gradual discontinuation of antidepressants. American Journal of Psychiatry 167(8), 934-941. [Abstract]
Beghi, E., Bussone, G., D'Amico, D., et al. (2010) Headache, anxiety and depressive disorders: the HADAS study. Journal of Headache and Pain 11(2), 141-150. [Abstract]
Burton, C., Simpson, C. and Anderson, N. (2013) Diagnosis and treatment of depression following routine screening in patients with coronary heart disease or diabetes: database cohort study. Psychological Medicine 43(3), 529-537. [Abstract]
Coupland, C., Dhiman, P., Barton, G., et al. (2011) A study of the safety and harms of antidepressant drugs for older people: a cohort study using a large primary care database. Health Technology Assessment 15(28), 1-202. [Abstract] [Free Full-text]
Dickinson, R., Knapp, P., House, A.O., et al. (2010) Long-term prescribing of antidepressants in older population: a qualitative study. British Journal of General Practice 60(573), e144-e155. [Abstract] [Free Full-text]
El Marroun, H., Jaddoes, V.W.V., Hudziak, J.J., et al. (2012) Maternal use of selective serotonin reuptake inhibitors, fetal growth, and risk of adverse birth outcomes. Archives of General Psychiatry 69(7), 706-714. [Abstract]
Gallagher, P.J., Castro, V., Fava, M., et al. (2012) Antidepressant responses in patients with major depression exposed to NSAIDs: a pharmacovigilance study. American Journal of Psychiatry 169(10), 1065-1072. [Abstract]
Hamer, M., Batty, G.D., Seldenrijk, A. and Kivimaki, M. (2011) Antidepressant medication use and future risk of cardiovascular disease: the Scottish Health Survey. European Heart Journal 32(4), 437-442. [Abstract] [Free Full-text]
Kivimaki, M., Hamer, M., Batty, G.D., et al. (2010) Antidepressant medication use, weight gain and risk of type 2 diabetes mellitus: a population-based study. Diabetes Care 33(12), 2611-2616. [Abstract] [Free Full-text]
Martinez, C., Assimes, T.L., Mines, D., et al. (2010) Use of venlafaxine compared with other antidepressants and the risk of sudden cardiac death or near death: a nested case-control study. BMJ 340, c249. [Abstract] [Free Full-text]
Murakami, K., Miyake, Y., Sasaki, S., et al. (2010) Fish and n-3 polyunsaturated fatty acid intake and depressive symptoms: Ryukyus child health study. Pediatrics 126(3), e623-e630. [Abstract] [Free Full-text]
Rubin, R.R., Ma, Y., Payrot, M., et al. (2010) Antidepressant medicine use and risk of developing diabetes during the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study. Diabetes Care 33(12), 2549-2551. [Abstract] [Free Full-text]
Schneeweiss, S., Patrick, A.R., Solomon, D.H., et al. (2010) Variation in the risk of suicide attempts and completed suicides be antidepressant agent in adults: a propensity score-adjusted analysis of 9 years' data. Archives of General Psychiatry 67(5), 497-506. [Abstract] [Free Full-text]
Tamburrino, M.B., Lynch, D.J., Nagel, R.W., and Smith, M.K. (2009) Primary care evaluation of mental disorders (PRIME-MD) screening for minor depressive disorder in primary care. Primary Care Companion to the Journal of Clinical Psychiatry 11(6), 339-343. [Abstract] [Free Full-text]
New policies
The Government has published its Mental Health Strategy:
No health without mental health: a cross-Government mental health outcomes strategy for people of all ages.
Reference: HMG and DH (2011) No health without mental health: a cross-Government mental health outcomes strategy for people of all ages. Department of Health. www.dh.gov.uk [Free Full-text]
New safety alerts
May 2010: The Medicines and Healthcare products Regulatory Agency (MHRA) has advised that:
Epidemiological studies, mainly in patients aged 50 years or older, show a small increased risk of fractures associated with the use of TCAs and SSRIs.
The odds for fracture associated with current SSRI use varied between 1.4 (95% CI 0.93 to 2.24) and 2.4 (95% CI 2.0 to 2.7).
The odds for fracture associated with current TCA use varied between 1.2 (95% CI 0.7 to 2.2) and 2.2 (95% CI 1.8 to 2.8).
The mechanism leading to this increased risk is unclear.
Healthcare professionals should take this risk into account in their discussions with patients and in prescribing decisions.
Reference: MHRA (2010) Antidepressants: risk of fractures. Drug Safety Update 3(10), 3-4. [Free Full-text (pdf)]
Citalopram and escitalopram
December 2011: Lundbeck Limited (UK) in collaboration with the Medicines and Healthcare products Regulatory Agency (MHRA) have advised that escitalopram is associated with dose-dependent QT interval prolongation.
October 2011: Lundbeck Limited (UK) in collaboration with the Medicines and Healthcare products Regulatory Agency (MHRA) have advised that citalopram is associated with dose-dependent QT interval prolongation.
This new advice followed:
A review of spontaneously reported data which identified people who had had QT prolongation, and/or ventricular arrhythmias including Torsade de Pointes whilst taking citalopram or escitalopram.
An assessment of a study that found a dose-dependent increase in the QT interval.
A review of studies that found no added benefit in the treatment of depression at doses higher than 40 mg daily of citalopram.
The following advice has been issued to health care professionals about citalopram and escitalopram:
Dosage of citalopram:
The maximum dose of citalopram is now:
40 mg daily in adults aged 65 years and under.
20 mg daily in the elderly (over 65 years) and in people with reduced hepatic function.
Dosage of escitalopram:
The maximum dose of escitalopram:
Remains at 20 mg daily in adults aged 65 years and under.
Remains at 10 mg daily in people with reduced hepatic function.
Is now reduced to 10 mg daily in people aged over 65 years.
Contraindications:
Citalopram and escitalopram are now contraindicated:
In people with known pre-existing QT interval prolongation.
In people with congenital long QT syndrome.
If the person is already taking medication known to prolong the QT interval.
Cautions:
Caution is advised when prescribing citalopram or escitalopram in people at a higher risk than average of developing Torsade de Pointes. This includes people with:
Congestive heart failure.
Recent myocardial infarction.
Bradyarrhythmias.
Concomitant illness or medication causing a predisposition to hypokalemia or hypomagnesaemia.
Before starting treatment with citalopram or escitalopram:
Consider an ECG and measurement of the QT interval in people with cardiac disease.
Correct electrolyte imbalances such as hypokalaemia and hypomagnesaemia before starting treatment. Monitor serum magnesium in elderly people taking diuretics or proton pump inhibitors.
If cardiac symptoms such as palpitations, vertigo, syncope, or seizures develop during treatment, arrange for the person to have an ECG:
If the QTc interval (QT interval corrected for heart rate) is greater than 500 milliseconds, withdraw treatment gradually.
If the QTc interval is between 480 and 500 milliseconds, the risks and benefits of continuing treatment should be carefully considered, alongside options for dose reduction or gradual withdrawal.
References:
Lundbeck Limited (2011) Association of CIPRAMIL® (citalopram hydrobromide) with dose-dependent QT interval prolongation. Medicines and Healthcare products Regulatory Agency www.mhra.gov.uk [Free Full-text (pdf)]
Lundbeck Limited (2011) Association of escitalopram (Cipralex) with dose-dependent QT interval prolongation. Medicines and Healthcare products Regulatory Agency www.mhra.gov.uk [Free Full-text (pdf)]
MHRA (2011) Citalopram and escitalopram: QT interval prolongation — new maximum daily dose restrictions (including in elderly patients), contraindications, and warnings. Drug Safety Update 5(5), A1. [Free Full-text]
Changes in product availability
Seroquel® XL (quetiapine) tablets are now licensed as add-on treatment of major depressive episodes in people who have had a suboptimal response to antidepressant monotherapy (October 2010).
Goals and outcome measures
Goals
To identify people with depression
To restore health and function through the complete relief of symptoms
To treat depression effectively (to improve mood, social and occupational functioning, and quality of life)
To reduce the chance of relapse or recurrence
To reduce morbidity and mortality from attempted suicide
To minimize adverse effects of treatment
Audit criteria
The guidelines published by the National Institute for Health and Clinical Excellence (NICE), Depression: the treatment and management of depression in adults (CG90) [National Collaborating Centre for Mental Health, 2009a; NICE, 2009a] and Depression in adults with a chronic physical health problem (CG91) [NICE, 2009b], do not advise on specific audit criteria.
QOF indicators
| Indicator | Points | Payment stages |
|---|---|---|
| Depression | ||
| DEP 1The percentage of patients on the diabetes register and/or the CHD register for whom case finding for depression has been undertaken on 1 occasion during the preceding 15 months using two standard screening questions. | ||
| DEP 6In those patients with a new diagnosis of depression, recorded between the preceding 1 April and 31 March, the percentage of patients who have had an assessment of severity at the time of diagnosis using an assessment tool validated for use in primary care. | ||
| DEP 7In those patients with a new diagnosis of depression and assessment of severity recorded between the preceding 1 April to 31 March, the percentage of patients who have had a further assessment of severity 2–12 weeks (inclusive) after the initial recording of the assessment of severity. Both assessments should be completed using an assessment tool validated for use in primary care. | ||
NICE quality standards
NICE quality standards
People who may have depression receive an assessment that identifies the severity of symptoms, the degree of associated functional impairment and the duration of the episode.
Practitioners delivering pharmacological, psychological or psychosocial interventions for people with depression receive regular supervision that ensures they are competent in delivering interventions of appropriate content and duration in accordance with NICE guidance.
Practitioners delivering pharmacological, psychological or psychosocial interventions for people with depression record health outcomes at each appointment and use the findings to adjust delivery of interventions.
People with persistent subthreshold depressive symptoms or mild to moderate depression receive appropriate low-intensity psychosocial interventions.
People with persistent subthreshold depressive symptoms or mild depression are prescribed antidepressants only when they meet specific clinical criteria in accordance with NICE guidance.
People with moderate or severe depression (and no existing chronic physical health problem) receive a combination of antidepressant medication and either high-intensity cognitive behavioural therapy or interpersonal therapy.
People with moderate depression and a chronic physical health problem receive an appropriate high-intensity psychological intervention.
People with severe depression and a chronic physical health problem receive a combination of antidepressant medication and individual cognitive behavioural therapy.
People with moderate to severe depression and a chronic physical health problem with associated functional impairment, whose symptoms are not responding to initial interventions, receive collaborative care.
People with depression who benefit from treatment with antidepressants are advised to continue with treatment for at least 6 months after remission, extending to at least 2 years for people at risk of relapse.
People with depression whose treatment consists solely of antidepressants are regularly reassessed at intervals of at least 2 to 4 weeks for at least the first 3 months of treatment.
People with depression that has not responded adequately to initial treatment within 6 to 8 weeks have their treatment plan reviewed.
People who have been treated for depression who have residual symptoms or are considered to be at significant risk of relapse receive appropriate psychological interventions.
QIPP - Options for local implementation
First-choice antidepressant use in adults with depression or generalised anxiety disorder:
Review and, where appropriate, revise prescribing of antidepressants in adults to ensure that it is line with NICE guidance.
Background information
Definition
What is it?
Depression
Depression refers to a range of mental conditions characterized by persistent low mood, absence of positive affect (loss of interest and enjoyment in ordinary things and experiences), and a range of associated emotional, cognitive, physical, and behavioural symptoms. Symptoms occur on a continuum of severity, and day to day functioning is often impaired.
Depression is usually defined, and its severity categorized, by one of two main classification systems: the fourth edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) [American Psychiatric Association, 2000], or the tenth revision of the International Classification of Diseases (ICD-10) [WHO, 1992]. In both systems, symptoms must have been present for at least 2 weeks. The National Institute for Health and Clinical Excellence (NICE) recommends using DSM-IV [NICE, 2009a]. For details, see Assessment and diagnosis.
Major depressive episodes
Are 'clinically important' episodes of depression in DSM-IV which may be mild, moderate, or severe. They are termed depressive episodes in ICD-10.
Subthreshold depressive symptoms
People may present with symptoms of depression that do not meet the DSM-IV criteria for depression.
Persistence of these symptoms for 2 years has been referred to as dysthymia. However, NICE recommends that a more appropriate term is 'persistent subthreshold depressive symptoms'.
Chronic depression
Depression is said to be chronic if it persists for more than 2 years.
Seasonal affective disorder
Seasonal affective disorder is diagnosed when the person has recurrent episodes of depression which occur annually at the same time each year (usually appearing in winter and remitting in spring). Atypical depressive symptoms are common, in particular decreased activity and weight gain. Although a high prevalence of seasonal depression has been reported in UK surveys, opinions in Europe differ on whether this is a distinct diagnosis or a trait that occurs in those with or without a depressive disorder.
Remission and recovery
Remission is the absence of depressive symptoms in a person who has been depressed, but there is little consensus as to how long this should be.
In DSM-IV, the person is said to be in full remission if depressive symptoms have been absent for at least 2 months. Partial remission is said to be present if symptoms are still present but do not meet the full criteria for diagnosing depression, or if symptoms are absent but 2 months has not yet passed.
There is no evidence-based consensus as to how free of symptoms a person needs to be (and for how long) in order to declare recovery and allow distinction from the fluctuating course of a single episode. NICE takes the position that at least 2 months of full or partial remission is required to distinguish episodes.
Recurrence
Recurrence describes a further episode of depression following recovery, as opposed to a relapse of the same episode.
Differentiating relapse from recurrence can be challenging.
Prevalence
How common is it?
Depression is the fourth leading cause of disability and disease worldwide.
World Health Organization (WHO) projections indicate that depression will be the highest ranked cause of disease burden in developed countries by the year 2020.
Depression is the third most common reason for consultation in general practice in the UK and is the most common psychiatric disorder.
Each year, 6% of adults experience an episode of depression, and over the course of their lifetime more than 15% of the population will experience an episode.
An episode of depression serious enough to require treatment occurs in about one in four women and one in ten men at some point in their lives.
About two-thirds of adults will at some time experience depressed mood of sufficient severity to interfere with their normal activities.
In the UK, in the year 2000, the point prevalence for depression among those 16–74 years of age was 2.6% [Singleton et al, 2001]. When the less specific and broader category of 'mixed depression and anxiety' was included, these figures rose dramatically to 11.4% (males 9.1%, females 13.6%).
A WHO study found a prevalence of depression of 23% in people with two or more chronic physical disorders, whereas depression was reported in only 3.2% of healthy controls [Moussavi et al, 2007].
Prevalence rates have consistently been found to be 1.5–2.5 times higher in women than in men in the age group 18–64 years.
The incidence of dysthymia (subthreshold depressive symptoms persisting for more than 2 years) increases with age; it is estimated that 2.5–5% of people will experience dysthymia during their lifetime [Waraich et al, 2004].
Causes
What causes it?
The cause of depression is unknown but is likely to result from a complex interaction of biological, psychological, and social factors.
Genetic factors play a part, but without a clear pattern of inheritance.
Personality factors have been implicated.
Psychosocial issues (such as unemployment, divorce, and poverty) increase vulnerability.
Failure of adaptive mechanisms to stressors may be involved.
Chronic comorbidities such as diabetes, chronic obstructive pulmonary disease, and cardiovascular disease make depression more likely. People with chronic pain syndromes are particularly likely to become depressed.
A past head injury is also a risk factor for depression and suicide [Wasserman et al, 2008].
Hypopituitarism following traumatic head injury is often unrecognized and may cause depression [Bavisetty et al, 2008].
Complications
What are the complications?
Depression is a major cause of impaired quality of life, reduced productivity, and increased mortality.
It negatively impacts health to a substantially greater degree than the major chronic physical illnesses (angina, arthritis, asthma, and diabetes) [Moussavi et al, 2007].
It exacerbates the pain, distress, and disability associated with physical diseases and increases the risk of death for a range of comorbid conditions [Cassano and Fava, 2002] including coronary heart disease [Nicholson et al, 2006].
Depressive symptoms tend to predict mortality in older people [St. John and Montgomery, 2009].
The ability to work effectively is undermined and there is a loss of contribution to society.
Negative public stereotypes can lead to further discrimination and loss of employment.
Loss of self-confidence, stigma, anxiety symptoms, and substance misuse may cause further longer-term impairment in social functioning [Sartorius, 2001].
Depression may result in marital break-up and family problems. Parental depression may lead to neglect of children [Ramchandani and Stein, 2003].
Suicide accounts for nearly 1% of all deaths in the general population, and nearly two-thirds of this figure occurs in depressed people [Sartorius, 2001]. There is a four-times higher risk of suicide in depressed people compared with the general population (2.2% compared with less than 0.5%), and the risk of suicide is nearly 20-times higher in the most severely ill [Bostwick and Pankratz, 2000]. Mortality from suicide is reported to be as high as 15% in people with depression severe enough to require hospitalization.
Prognosis
What is the prognosis?
The average length of an episode of depression is 6–8 months, and for many it will be mild.
Milder forms of depression are more likely to go undetected but are also more likely to recover spontaneously.
For a third of people with depression, however, it will be moderate or severe and significantly impact on their daily lives.
At least 50% of all people affected by a first episode of depression go on to have at least one more episode.
After a second episode of depression, the risk of a further recurrence increases to 70%; after a third episode, this risk increases to 90% [Kupfer, 1991].
Onset before 20 years of age, or onset in old age, increases vulnerability to relapse, and outcomes deteriorate with recurrent episodes.
At least 10% of people with depression go on to experience chronic or persistent depression [Kessler et al, 2003].
Up to 10% of depressed people subsequently have hypomanic episodes [Kovacs, 1996].
In people with recurrent episodes of depression that demonstrate a seasonal pattern, up to half lose the seasonal variation over the longer term [Magnusson and Partonen, 2005].
About 70% of people with dysthymia (persistent subthreshold depressive symptoms for more than 2 years) go on to develop the full criteria for depression [Waraich et al, 2004].
Detection, assessment, diagnosis
Detection, assessment, and diagnosis of depression
Detection
How do I identify people for further assessment?
Be aware of barriers to identifying people with depression, such as:
Limited consultation time.
An assumption that depression is a normal response to stress.
A reluctance to identify depression because 'nothing can be done'.
People presenting with atypical or predominantly physical symptoms.
Significant communication difficulty.
Be alert to the presence of depression, particularly in high-risk groups, such as people with:
A history of depression, suicide attempt, or any form of abuse (sexual, physical, or substance).
Significant physical illness (such as coronary heart disease, chronic pain syndrome).
Other mental health problems, such as dementia.
A family history of depression.
Other potential clues, such as frequent visits to the GP or emergency department.
Consider asking these questions:
During the last month have you often been bothered by:
Feeling down, depressed, or hopeless?
Having little interest or pleasure in doing things?
An answer of 'yes' to either question indicates that the person may be depressed and should prompt a more detailed assessment.
Negative responses, however, do not exclude depression; further assessment is indicated if depression is still suspected.
If the person has a chronic physical health problem and answers 'yes' to either of the questions, asking three further questions can help improve the accuracy of detection:
During the last month, have you often been bothered by:
Feelings of worthlessness?
Poor concentration?
Thoughts of death?
If depression is suspected, either clinically or from the results of the depression identification questions, the person should be assessed further by an appropriate healthcare professional.
Basis for recommendation
Basis for recommendation
These recommendations are based on guidelines published by the National Institute for Health and Clinical Excellence (NICE) — Depression: the treatment and management of depression in adults [National Collaborating Centre for Mental Health, 2009a; NICE, 2009a] and Depression in adults with a chronic physical health problem [National Collaborating Centre for Mental Health, 2009b; NICE, 2009b].
Barriers to detecting depression
It is estimated that up to 50% of people with depression are not recognized in primary care [National Collaborating Centre for Mental Health, 2009a].
At least two-thirds of depressed people who see their GP present with physical/somatic symptoms rather than psychological symptoms and are less likely to be recognized as being depressed [National Collaborating Centre for Mental Health, 2009a].
Healthcare professionals may have personal barriers which can impede the consultation:
In the limited time available for the consultation, healthcare professionals may be wary of opening a 'Pandora's box' and collude with the patient in 'therapeutic nihilism' — some healthcare professionals are still to be convinced of depression as a clinical condition, may consider depression to be a normal response to difficult times, and may be sceptical of treatment options [Burroughs et al, 2006].
Dissatisfaction with availability of psychological interventions.
A meta-analysis of 41 studies suggests that GPs are good at ruling out depression in most people who are not depressed, and that misidentifications (false positives) outnumber missed cases (false negatives) [Mitchell et al, 2009]. The undetected cases are more likely to be milder forms of depression [Kessler et al, 2003].
Identifying high-risk groups
People with long-term physical health problems are particularly vulnerable to depression (see Causes) and the General Medical Services contract includes routine assessment of people with certain chronic conditions, such as diabetes and coronary heart disease, for the presence of depression [BMA and NHS Employers, 2012].
Use of case-identification questions
A 'yes' response to one of the two questions has high specificity for depression (0.95, 95% CI 0.91 to 0.97) but low sensitivity (0.66, 95% CI 0.55 to 0.76) [National Collaborating Centre for Mental Health, 2009a].
Specificity may be further improved with the use of an additional question, 'Is this something with which you would like help?' [Arroll et al, 2005]. This is not recommended by NICE, however, as evidence supporting its use is provided by just one study.
Practitioners should be aware of the limitations of such ultra-short identification tests [Mallen and Peat, 2008]. They may be a useful entry point in a time-limited consultation, but all such measures may promote oversimplification, diverting practitioners away from broader psychosocial areas.
In people with chronic physical health problems, somatic symptoms may arise because of the comorbid physical problem rather than depression. Three further questions are asked, making a total of five mood/cognitive symptoms, but excluding the four somatic symptoms. A score of 3 out of 5 produces 94% agreement with DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) major depression [Zimmerman et al, 2006]. These additional questions are recommended to reduce false positives and reduce the known difficulty of diagnosing depression in people with a chronic physical health problem [National Collaborating Centre for Mental Health, 2009b; NICE, 2009b].
Assessment and diagnosis
How do I assess and confirm the diagnosis of depression?
Diagnosis should not rely upon a symptom count alone.
Detailed assessment of severity, duration, and course is needed to confirm the diagnosis and guide management.
Severity of symptoms and functional impairment.
Validated questionnaires may be part of this process.
Symptoms should be present for most of every day and be assessed for how they impact on function.
Duration and development of the condition.
Course — history and previous response to treatment.
Consider contributory factors, underlying causes, and alternative diagnosis.
Symptoms
The key symptoms to be assessed in order to make a diagnosis of depression using DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) criteria are shown below.
Ask the person if they have one of the core symptoms:
Persistent sadness or low mood nearly every day.
Loss of interests or pleasure in most activities.
If either of these core symptoms have been present most days, most of the time, for at least 2 weeks, ask about other symptoms of depression.
'Major depressive episode' is diagnosed if the person has at least five out of nine symptoms, with at least one of these a core symptom.
Both core symptoms would be expected to be present in people with moderate or severe depressive episodes.
Symptoms need to be experienced to a sufficient degree of severity and persistence to be counted as definitely present.
However, if the person does not fulfil these criteria (subthreshold depressive symptoms), they should not be dismissed as they may still have potential for considerable morbidity.
Older people are least likely to report psychological symptoms (such as worry), and may present more with physical symptoms.
Depression can present with atypical features (atypical depression), such as over-eating, over-sleeping, and mood reactivity.
Severity
Severity of depression is likely to be greater when more symptoms are present, but other factors should also be taken into account such as the type of symptoms experienced, functional and social impairment, and duration of symptoms.
Subthreshold depression — less than the five symptoms required to make a diagnosis of major depression.
Mild depression — few, if any, symptoms in excess of the five required to make the diagnosis, and only minor functional impairment.
Moderate depression — symptoms or functional impairment between mild and severe. Some symptoms would be expected to be marked.
Severe depression — several symptoms in excess of those required to make the diagnosis. Some symptoms would be expected to be severe and markedly interfere with functioning.
Depression questionnaires can also give some indication of severity, but should not be used alone to guide management decisions.
Assess the risk of suicide.
Duration
Symptoms should have been present for at least 2 weeks before a diagnosis of depression is made.
If the person has depression which has gone on for more than 2 years, they are said to have chronic depression.
People may have chronic subthreshold depressive symptoms (sometimes termed dysthymia).
The 2-year cut off is arbitrary, and in practice the duration of symptoms should be considered in the context of the severity and course of the illness.
Course
Assess the course of the symptoms (for example worsening, static, improving), and whether people with mild symptoms have subthreshold depressive symptoms or are presenting with partially resolved depression.
Diagnosis of depression using DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) criteria:
DSM-IV major/minor depressive disorder:
Depressed mood by self-report or observation by others*
Loss of interest or pleasure in activities*
Fatigue/loss of energy
Worthlessness/excessive or inappropriate guilt
Recurrent thoughts of death, suicidal thoughts, or actual suicide attempts
Diminished ability to think/concentrate or indecisiveness
Psychomotor agitation or retardation
Insomnia/hypersomnia
Significant appetite and/or weight loss
*Core symptoms. In DSM-IV there are 2 core symptoms. One must be present.
[American Psychiatric Association, 2000]
Other areas in history to consider
Other areas in history to consider
History
Is there a history of mental health disorder?
Is there a history of mood elevation indicative of bipolar disorder?
What is the historical pattern of illness?
What treatments (including herbal treatments such as St John's wort) have been tried?
What was the response to treatment?
Is there seasonal variance?
Social context
Do living conditions, economic circumstances, or social isolation contribute to the clinical picture?
Is the diagnosis complicated by important individual factors, such as relationship problems?
Is there another premorbid context such as sexual abuse?
Comorbid/underlying conditions
Is there an additional comorbid psychiatric diagnosis, such as anxiety or social phobia?
Could symptoms be due to the direct physiological effects of alcohol or substance misuse, or prescribed medication?
Could symptoms be due to an underlying medical condition (for example hypothyroidism)?
Are symptoms better accounted for by bereavement?
Depression questionnaires
Depression questionnaires
Depression questionnaires can be helpful in detecting depression and in assessing severity, but should not be used alone to determine the presence of depression which needs treatment.
The three recommended questionnaires, which are validated for use in primary care, are PHQ-9 (Patient Health Questionnaire 9), HADS (Hospital Anxiety and Depression Scale), and BDI-II (Back Depression Inventory-II).
PHQ-9
A nine-item, self-administered scale, which scores severity using DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) criteria.
The maximum score is 27.
A score of 12 is the recommended threshold for considering intervention.
It can be downloaded free of charge from www.depression-primarycare.org.
HADS
A self-administered scale, with 14 items in total (seven covering depression and seven covering anxiety).
The maximum score for each subscale is 21.
For the HADS depression subscale (HADS-D), a score of 10 is the recommended threshold for considering intervention.
It is available to purchase from http://shop.gl-assessment.co.uk.
BDI-II
A 21-item, self-administered scale that uses DSM-IV criteria.
The maximum score is 63.
A score of 20 is the recommended threshold for considering intervention.
It is available to purchase from www.psychcorp.co.uk.
Basis for recommendation
Basis for recommendation
These recommendations are based on guidelines published by the National Institute for Health and Clinical Excellence (NICE) — Depression: the treatment and management of depression in adults [National Collaborating Centre for Mental Health, 2009a; NICE, 2009a] and Depression in adults with a chronic physical health problem [National Collaborating Centre for Mental Health, 2009b; NICE, 2009b].
Basis for classification system
A system that links clinical presentation to root aetiology, or which has been shown to predict the response to treatment, remains elusive. Defining a threshold where mood changes become clinically significant is problematic, and arbitrary lines (which may not be clinically meaningful) are sometimes drawn.
Depression is usually defined by one of two main classification systems:
The fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) [American Psychiatric Association, 2000].
The tenth revision of the International Classification of Diseases (ICD-10) [WHO, 1992].
Both systems describe a range of accompanying symptoms which classify depression according to severity as mild, moderate, or severe.
People diagnosed as having depression by either of these systems are said to have 'major' depression. However the term 'major' is often omitted, which can create confusion. The alternative term of clinical depression is not used by NICE.
The 2009 NICE guideline [NICE, 2009a] adopts the DSM-IV criteria in preference to the previous use of ICD-10 in the 2004 guideline [NICE, 2004b]. NICE prefers DSM-IV because the evidence base for treatments refers, to a larger extent, to these criteria.
Clinicians should be aware of the higher threshold for diagnosing depression with DSM-IV compared with ICD-10. A German primary care-based study found that 2–3 times more people were diagnosed as depressed using ICD-10 than with DSM-IV, although most of this excess was in people with mild depression by ICD-10 criteria [Wittchen et al, 2001].
Subclassification of depression has been based historically on symptom clusters and assumed aetiology. This is somewhat lacking in usefulness, including unhelpful terms such as reactive and endogenous depression.
NICE accepts the usefulness of terms such as depression with atypical features and depression with a seasonal pattern.
Depression with atypical features is recognized in DSM-IV.
Classic atypical depressive features are said to be over-eating, over-sleeping, and mood reactivity particularly in those with an over-sensitivity to rejection.
People with atypical features are more often female, have a younger age of onset, and demonstrate more severe psychomotor slowing.
Major depression with a seasonal pattern is recognized in DSM-IV.
The term 'seasonal affective disorder' (SAD) was introduced in 1984 [Rosenthal et al, 1984]. Symptoms usually present in winter and remit in spring, and atypical depressive symptoms are common (in particular decreased activity).
Although a high prevalence of seasonal depression has been reported in UK surveys, opinions in Europe differ on whether this is a distinct condition or a trait that appears anyway in those with or without depression [National Collaborating Centre for Mental Health, 2009a].
NICE does not use the terms mixed anxiety and depression or treatment-resistant depression.
Mixed anxiety and depression is a category in ICD-10.
It is not as clearly defined as the minor depression of DSM-IV, which is used as a research term only.
It is largely a diagnosis of exclusion in those with anxiety and depressive symptoms that are subthreshold for specific disorders.
It is a heterogeneous category with a lack of diagnostic stability over time and has therefore been excluded from the latest NICE guidance.
Treatment-resistant depression is a term that is no longer recommended as it is seen to be pejorative and representing an unhelpful model which can interfere with good care. NICE prefers to 'approach the problem of inadequate response to treatment from the direction of next-step treatment options rather than a category of patient' [National Collaborating Centre for Mental Health, 2009a].
Basis for diagnosing subthreshold depressive symptoms and persistent subthreshold depressive symptoms (dysthymia)
The term 'subthreshold depression' is potentially confusing as there is no clearly accepted definition. The closest defined complex is 'minor depression' with at least two but less than five symptoms, but this is only used as a research diagnosis in DSM-IV.
There is no meaningful cut-off between subthreshold depressive symptoms and mild 'major' depression in routine practice. Indeed, there is an overlap with ICD-10 which defines mild depression with four symptoms.
Dysthymia appears as a category in both DSM-IV and ICD-10, acknowledging that subthreshold symptoms may become chronic and may require treatment even if fairly mild. NICE recommends the term persistent subthreshold depressive symptoms over dysthymia.
It is characterized by at least 2 years of depressed mood for more days than not and which is not the consequence of a partially resolved 'major' depression.
At least two but less than five symptoms are required for the diagnosis.
People with dysthymia are usually able to cope with everyday life.
The difficulty in making a definitive diagnosis has contributed to confusion and the diagnosis has not been hugely embraced in UK practice.
NICE concluded that there is no convincing evidence that antidepressants benefit people with recent-onset subthreshold depressive symptoms, but they are effective in people with persistent subthreshold depressive symptoms (dysthymia) [National Collaborating Centre for Mental Health, 2009a]. Therefore, NICE recommends against routine use of antidepressants, but they should be considered where symptoms persist.
People with subthreshold depressive symptoms are candidates for the same treatment options as those with mild depression. However, exactly how long to wait before offering medication or low intensity psychological treatment is currently unclear.
Use of depression questionnaires
Questionnaires can help identify people with depression, and indicate severity. They should not, however, be used as the sole method for diagnosing depression and for deciding on whether to offer treatment.
In the Quality and Outcomes Framework guidance for the General Medical Services contract 2012/13, the PHQ-9 (Patient Health Questionnaire 9), HADS (Hospital Anxiety and Depression Scale), and BDI-II (Back Depression Inventory, Second Edition) are recommended as validated measures for use in primary care [BMA and NHS Employers, 2012].
These different scales all seem to have reasonable sensitivity and specificity for detecting depression.
PHQ-9 — sensitivity 0.82 (95% CI 0.77 to 0.86) and specificity 0.83 (95% CI 0.76 to 0.88) [National Collaborating Centre for Mental Health, 2009a].
HADS — sensitivity 0.90 and specificity 0.86 based on one study [BMA and NHS Employers, 2012]. NICE did not quote any figures because the results of the 21 identified studies were too heterogeneous for meta-analysis.
BDI-II — sensitivity 0.85 (95% CI 0.79 to 0.90) and specificity 0.83 (95% CI 0.70 to 0.91) [National Collaborating Centre for Mental Health, 2009a].
Comparing PHQ-9 and HADS (the two most commonly-used measures):
A study found that both scales accurately reflected changes in severity of depression. However, PHQ-9 identified 74% of 544 people as needing antidepressants compared with 37% using HADS [Cameron et al, 2008].
Assessing risk of suicide
How do I assess the risk of suicide?
Actively seek out symptoms by directly asking people with depression about suicidal ideation and current intent.
Not asking about suicide when there are signs of depression is like not asking about allergies when prescribing.
Ask if the person feels hopeless or that life is not worth living.
Do not avoid the word 'suicide'.
Suggested questions are:
Do you ever think about suicide?
Have you made any plans for ending your life?
Do you have the means for doing this available to you?
What has kept you from acting on these thoughts?
Follow up on 'not really' answers.
Regularly reassess the risk of suicide throughout the course of treatment.
Be aware of danger periods such as initiating treatment, changes in treatment, or increased personal stress.
Identify risk factors that increase the risk of suicide (see Table 1), particularly previous attempts at suicide or self-harm, or a feeling of hopelessness.
Assess adequacy of social support and current personal circumstances.
Identify factors that reduce the risk of suicide, including:
Good social support.
Responsibility for children.
Table 1. Risk factors for suicide.| Social characteristics | History | Clinical/diagnostic features |
|---|---|---|
| Male genderYoung age (< 30 years)Advanced ageSingle or living alone | Prior suicide attempt(s)Family history of suicideHistory of substance abuseRecently started on antidepressants | HopelessnessPsychosisAnxiety, agitation, panic attacksConcurrent physical illnessSevere depression |
[British Columbia Medical Association, 2004; Singapore Ministry of Health, 2004; NICE, 2009a]
Basis for recommendation
Basis for recommendation
These recommendations are based on the guideline from the National Institute for Health and Clinical Excellence (NICE) — Depression: the treatment and management of depression in adults [National Collaborating Centre for Mental Health, 2009a; NICE, 2009a], and expert opinion taken from Suicide risk: a guide for primary care and mental health staff [Newcastle North Tyneside and Northumberland Mental Health NHS Trust, 2001].
The use of risk factors in the assessment of suicide risk is acknowledged in a number of guidelines and review articles [Newcastle North Tyneside and Northumberland Mental Health NHS Trust, 2001; NZGG, 2003; Stovall and Domino, 2003; British Columbia Medical Association, 2004; Schulberg et al, 2004; DH, 2007b].
It is important to assess suicide risk in people presenting with depression, particularly those with comorbidities.
Depression is probably the most important risk factor for suicide [Knapp and Ilson, 2002].
Suicide accounts for nearly 1% of all deaths, and nearly two-thirds of this figure occur in depressed people [Sartorius, 2001].
It is particularly important to detect depression and assess suicide risk in people with chronic physical illness. Large population-based epidemiological studies have reported higher suicide risk in people with depression who also have chronic illnesses (such as cancer, diabetes, end-stage renal disease, and stroke) [National Collaborating Centre for Mental Health, 2009b].
'Not asking about suicide when there are signs of depression is like not asking about allergies when prescribing. Follow up on "not really" answers' [Linsley, Personal Communication, 2009].
Investigations
What investigations should I do for depression?
There is no specific recommended laboratory investigation for depression.
Investigations to rule out possible organic causes are not routinely indicated, but are guided by clinical presentation.
The threshold for investigation is lower in the elderly (such as suspicion of anaemia or hypothyroidism in people who are fatigued).
Basic laboratory tests that may be indicated are:
Biochemistry: blood glucose, urea and electrolytes, creatinine, liver function tests, thyroid function tests, calcium levels.
Haematology: full blood count and erythrocyte sedimentation rate.
A range of other tests may follow depending on the clinical picture, such as magnesium levels, HIV or syphilis serology, or drug screening.
If the presentation or physical examination has unusual or unexpected features (such as unexplained headache and personality changes), consider seeking specialist advice on whether investigations such as brain imaging are indicated.
Basis for recommendation
Basis for recommendation
The National Institute for Health and Clinical Excellence (NICE) makes no specific recommendations regarding laboratory tests for depression.
Investigations are not routinely indicated in people with depression, but may be necessary to exclude other causes for the symptoms or conditions known to be associated with depression (see Differential diagnosis).
The investigations outlined are those recommended in a handbook on laboratory investigation of people with psychiatric disorders [Foster, 2008].
Differential diagnosis
What is the differential diagnosis?
Consider coexisting psychological and psychiatric disorders, such as bipolar disorder, anxiety, dementia, eating disorders, post-traumatic stress disorder, and alcohol abuse.
Grief reaction can be difficult to distinguish from depression.
Dementia may present as depression and vice versa [National Health Committee, 1996].
Approximately a third of people with dementia develop depressive symptoms. Pseudodementia describes cognitive impairment due to depression in the elderly.
Distinguishing depression from dementia can be difficult, as they share symptomatology (disorientation, memory loss, and distractability).
A primary diagnosis of depression is suggested by:
Preservation of a reasonable memory.
Personal or family history of depression.
A successful trial of treatment for depression which alleviates dementing symptoms.
Parkinson's Disease is associated with mild dementia in approximately a third of people, and tends to become more severe in the end stages. Approximately half of people with Parkinson's disease with dementing symptoms develop depression during their illness [National Health Committee, 1996]. See the CKS topic on Parkinson's disease.
Consider underlying medical conditions with known associations with depression, including [National Health Committee, 1996; Foster, 2008]:
Chronic diseases such as diabetes and cardiac disease.
Cerebrovascular disease (stroke, subarachnoid haemorrhage).
Certain endocrine disorders (hyperthyroidism, Cushing's syndrome, adrenal insufficiency, hyperparathyroidism).
Cancer, especially pancreatic.
Autoimmune conditions.
Hypopituitarism following traumatic head injury is often unrecognized and may cause depression [Ghigo et al, 2005; Agha and Thompson, 2006; Klose et al, 2007; Bavisetty et al, 2008].
Consider the effect of substances and adverse drug effects [Foster, 2008].
Carbon monoxide poisoning can present with irregularities of the mental state (see the CKS topic on Carbon monoxide poisoning).
Substance misuse (for example alcohol, anabolic steroids, cannabis, cocaine, narcotics) is frequently associated with depression.
Drug adverse effects are an uncommon cause of depression. Examples include centrally-acting antihypertensives (such as methyldopa), lipid-soluble beta-blockers (such as propranolol), central nervous system depressants, opioid analgesics, and isotretinoin.
Management
Management
Scenario: New or initial management: covers the early management of depression.
Scenario: Ongoing management: covers management of the review period, use of different interventions, the available and recommended treatment strategies, and how to minimize the risk of relapse.
Scenario: Seasonal affective disorder: covers the management of people with seasonal affective disorder.
Scenario: Bereavement: covers the management of people with depression associated with bereavement.
Scenario: Association with other psychological disorders: covers the management of depression associated with other psychological disorders.
Scenario: New or initial management
Scenario: New or initial management of depression
General principles of care
What general principles of care should I follow?
When working with people with depression and their families and carers:
Be aware of possible stigma and discrimination associated with depression.
Ensure that written information is provided in the appropriate language and is culturally sensitive.
Be aware of danger periods.
Advise the person, and their family or carers, to be vigilant for suicidal ideation, particularly during high-risk times such as initiation of treatment, changes in treatment, or increased personal stress.
Actively seek out symptoms of suicidal intent by directly asking people with depression about it (see Assessing risk of suicide).
Be aware of the needs of families and carers, and consider:
Providing written and verbal information about depression and its treatment, and about self-help groups, support groups, and other resources.
Providing information on local family or carer support groups and voluntary organizations.
Offering a carer's assessment.
Negotiating confidentiality and sharing of information between the person and their family or carers.
Ensure that the person can give meaningful and informed consent, especially if they have severe depression or are subject to the Mental Health Act.
If the person does not have the capacity to make decisions, further advice is available from www.dh.gov.uk/consent.
The code of practice that accompanies the Mental Capacity Act of 2005 contains practical guidance; it can be found at www.dca.gov.uk (pdf).
Additional information is available at www.publicguardian.gov.uk.
If there is an underlying physical health problem:
Always consider possible contributory factors and the role of any prescribed medication.
Obtain clear agreement with secondary care about where the responsibility for monitoring and treatment lies.
When discussing choices of intervention, take into account:
The person's preference, exploring treatment options with hope and optimism.
Duration of symptoms and their trajectory.
Previous course and response to treatment.
Likelihood of adherence to the intervention.
Consideration of adverse effects.
Always consider giving sleep hygiene advice.
Establishing regular sleep patterns.
Avoiding excess eating, smoking, or alcohol before sleep.
Creating a proper environment for sleep.
Taking regular physical exercise.
Use a stepped-care approach to the management of depression, which draws attention to the different needs that depressed people have at different stages of their depression, and the responses that are required from services (see Table 1).
Table 1. The stepped-care approach to the management of depression.| Stage of depression | Intervention |
|---|---|
| Step 1: all known and suspected presentations of depression. | Assessment, support, psychoeducation, active monitoring, and referral for further assessment and interventions. |
| Step 2: persistent subthreshold depressive symptoms; mild-to-moderate depression. | Low-intensity psychological and psychosocial interventions, medication, and referral for further assessment and interventions. |
| Step 3: persistent subthreshold depressive symptoms or mild-to-moderate depression with inadequate response to initial interventions; moderate and severe depression. | Medication, high-intensity psychological interventions, combined treatments, collaborative care, and referral for further assessment and interventions. |
| Step 4: severe and complex depression; risk to life; severe self-neglect. | Medication, high-intensity psychological interventions, electroconvulsive therapy, crisis service, combined treatments, and multiprofessional and inpatient care. |
Self-help and support groups
Self-help and support groups
Self-help involves a range of approaches in varying intensity.
When these materials are entirely managed by the individual, this is referred to as 'pure self-help'.
With some limited directional input from a healthcare professional or paraprofessional, this low intensity psychological intervention is referred to as guided self-help [Gellatly et al, 2007].
People with depression may benefit from receiving information about self-help groups, support groups, and other available resources (locally and nationally) that provide support, activities, and social contact in order to improve the outcome of depression.
There are many organizations offering materials and local group peer support to people with depression (see Table 1), which are likely to be beneficial — although there is no clear research-based evidence for their effectiveness.
Table 1. Self-help groups.| Support group | Website |
|---|---|
| Mental Health Foundation | www.mentalhealth.org.uk |
| MIND | www.mind.org.uk |
| Depression Alliance | www.depressionalliance.org |
Basis for recommendation
Basis for recommendation
These recommendations are based on guidelines published by the National Institute for Health and Clinical Excellence (NICE) — Depression: the treatment and management of depression in adults [National Collaborating Centre for Mental Health, 2009a; NICE, 2009a] and Depression in adults with a chronic physical health problem [National Collaborating Centre for Mental Health, 2009b; NICE, 2009b].
Choice of specific intervention
Which specific intervention should I offer?
General issues to consider:
Refer with appropriate urgency if the clinical situation is severe or there is suicidal risk.
Be aware that availability and arrangements for accessing psychological interventions may vary according to locality.
Choice of specific psychological intervention is likely to be made following an assessment by the psychological service the person is referred to.
In all cases, follow general principles of care.
Advise the person not to use St John's wort.
If, in the judgment of the healthcare practitioner, specific intervention for depression may not be needed, or the person has mild depression and declines intervention:
Consider a period of active monitoring.
Discuss the presenting problems and the person's concerns.
Provide information about the nature and course of depression.
Arrange follow up, normally within 2 weeks.
Consider contacting the person if they fail to attend follow-up appointments.
For people with persistent subthreshold depressive symptoms or mild-to-moderate depression:
Consider offering one or more low-intensity psychological interventions.
Individual guided self-help based on principles of cognitive behavioural therapy (CBT).
Computerized CBT.
A structured group-based physical activity programme.
Consider group-based CBT for those who decline low-intensity psychosocial interventions.
For people with a chronic physical health problem, also consider a group-based peer support programme, either alone or in combination with the above.
Do not use antidepressants routinely, but consider this for people with:
A history of moderate or severe depression.
Subthreshold depressive symptoms that have persisted for a long period (typically at least 2 years).
Mild depression that is complicating the care of a chronic physical health problem.
For people with moderate or severe depression:
If the person does not have a chronic physical health problem, offer an antidepressant and a high-intensity psychological intervention (CBT or interpersonal therapy).
If there is a chronic physical health problem, and
Depression is moderate — offer group-based CBT or another high-intensity psychological intervention (such as individual CBT or behavioural couples therapy).
Depression is severe — offer individual CBT combined with an antidepressant.
Basis for recommendation
Basis for recommendation
These recommendations are based on guidelines published by the National Institute for Health and Clinical Excellence (NICE) — Depression: the treatment and management of depression in adults [National Collaborating Centre for Mental Health, 2009a; NICE, 2009a] and Depression in adults with a chronic physical health problem [National Collaborating Centre for Mental Health, 2009b; NICE, 2009b].
St John's wort
NICE found evidence (from six randomized controlled trials, in 995 people) that, compared with placebo, St John's wort increased the likelihood of achieving a 50% reduction in symptoms of depression. However, there was insufficient evidence to determine if St John's wort was effective for achieving remission.
NICE advises that St John's wort should not be prescribed for treating depression because there is an absence of long-term data, uncertainty regarding which dose to use, the preparations available vary considerably with regard to potency, and there is potential for serious interactions with other drugs (such as oral contraceptives, anticoagulants, and anticonvulsants).
Antidepressants
Mild depression
For many people with mild depression, there is little clinically-relevant difference between antidepressants and placebo. Therefore, NICE recommends that antidepressants should not be prescribed for mild depression (because of the poor risk-benefit ratio), but may be considered for people with mild depression with persistent symptoms following other interventions.
Moderate-to-severe depression
Antidepressants are effective for treating people with moderate or severe depression. It is estimated that for people with moderate-to-severe depression: if no treatment is given, 20% will recover; if a placebo is given, 30% will respond; and if an antidepressant is given, 50% will respond [Anderson et al, 2008; Taylor et al, 2009]. This means that it is necessary to treat three people with an antidepressant compared with 'true' no treatment for one additional person to respond (NNT 3), and that it is necessary to treat five people with an antidepressant compared with placebo for one additional person to respond (NNT 5).
Subthreshold depressive symptoms
The somewhat arbitrary nature of the cut-off between subthreshold depression and mild major depression means that the treatment recommendations for subthreshold depressive symptoms are the same as with mild depression.
Antidepressants are no more effective than placebo for recent onset subthreshold depressive symptoms, but they may be effective for persistent subthreshold depressive symptoms (dysthymia).
Subthreshold symptoms of recent onset tend to improve without specific psychological intervention or medication, but it is not known how long to wait before offering treatment to people who are not improving.
Psychological treatments
NICE has updated the previous recommendation of 'watchful waiting' to a less passive process of 'active monitoring' which takes into account more involvement with assessment, advice, and support.
The benefits of cognitive behavioural therapy (CBT) in people with subthreshold depressive symptoms is unproven. Combined psychological and antidepressant treatment is no more effective than antidepressants alone in people with subthreshold depressive symptoms.
Low-intensity psychological treatments are recommended by NICE as the preferred initial option for treating subthreshold depressive symptoms and mild-to-moderate depression, based on a balance of effectiveness and cost implications.
Group-based CBT was viewed as more expensive than low-intensity interventions, and was placed at a higher threshold on grounds of cost-minimization.
High-intensity psychological treatments have been shown to be effective in moderate-to-severe depression, both alone and in combination with antidepressants.
Low- and high-intensity treatments are discussed in detail in the section on Psychological interventions.
Referral or seeking specialist advice
When should I refer or seek specialist advice?
If the person has taken an overdose, see the CKS topic on Poisoning or overdose.
Refer with appropriate urgency to a specialist mental health service if the person:
Is actively suicidal, or has a current suicide plan, or is at significant risk of self-harm.
Presents with considerable immediate risk to themselves or others.
Also consider urgent referral if the person has:
Psychotic symptoms (hallucinations, delusions).
Severe agitation accompanying severe symptoms.
Evidence of severe self-neglect.
Deteriorating personal circumstances exacerbating their mental illness.
If admission is thought to be necessary but the person refuses, see Crisis services and Compulsory admission.
Consider consulting with, or referring to, a practitioner with a special interest in treating depression or to a specialist service for any of the following:
Unclear diagnosis.
Recurrent episode of depression within 1 year of the last one.
History suggestive of bipolar disorder.
More persistent suicidal thoughts.
Comorbid substance, physical, or sexual abuse.
Severe psychosocial problems.
Rapid deterioration.
Cognitive impairment.
Referral is requested by the person with depression or their carers.
Crisis services
Crisis intervention
Crisis plans identify potential triggers and strategies to manage them. They should be shared with the GP and others relevant to the person's care.
Crisis resolution and home treatment teams (CRHTTs) may be an alternative to hospital admission, offering intensive home-based support in cases where this is considered to be the most appropriate setting.
CRHTTs may also facilitate early discharge from hospital; however, much of the data pertaining to their use refers to schizophrenia.
While there is insufficient evidence to clearly support their use in depression, the National Institute for Health and Clinical Excellence (NICE) advises that crisis teams may have a role for a small number of people with depression who require more intensive care.
Basis for recommendation
Basis for recommendation
These recommendations are based on guidelines published by the National Institute for Health and Clinical Excellence (NICE) — Depression: the treatment and management of depression in adults [National Collaborating Centre for Mental Health, 2009a; NICE, 2009a] and Depression in adults with a chronic physical health problem [National Collaborating Centre for Mental Health, 2009b; NICE, 2009b].
NICE found insufficient evidence from randomized controlled trials to determine the value of crisis resolution and home treatment teams for people with depression, but based the general recommendation on expert opinion.
Specialist services can offer:
Further drug treatments.
High-intensity psychological interventions.
Combined and augmented treatments.
Access to a crisis service.
In-patient care and electroconvulsive therapy.
Managing a person at risk of suicide
How do I respond to the risk of suicide?
If the person with depression is assessed to be at considerable immediate risk to themselves or others:
Refer with appropriate urgency to a specialist mental health service.
If admission is thought to be necessary but the person refuses, see Compulsory admission.
If the person has suicidal ideation:
Consider the toxicity of the prescribed medication and the quantities issued.
Consider the adequacy of, and access to, further support.
Advise on an appropriate course of action if the situation deteriorates.
Consider referral to a specialist service.
General measures
Do not offer false reassurance; rather, aim to problem-solve.
Ensure the person is aware of potential sources of help and has a point of contact for an appropriate healthcare professional.
Advise the person, as well as their family and carers, to seek help if the situation deteriorates.
Advise family members and carers to be vigilant for suicidal ideation.
Advise the person's family and carers to be aware of high-risk periods (such as when starting treatment, changes in treatment, increased personal stress) and to be vigilant for changes in mood, such as increased negativity, hopelessness, and suicidal intent.
Careful follow up
Ensure all episodes have adequate follow up. There is no such thing as a minor overdose.
Consider whether increased support is needed, such as more frequent contact (direct or telephone).
People started on antidepressants who are considered to be at risk of suicide or who are younger than 30 years of age should normally be seen after 1 week, then as frequently as is needed until the risk is no longer considered clinically important.
In cases of concern, use clinical judgement; an earlier review may be more appropriate.
Basis for recommendation
Basis for recommendation
These recommendations are based on guidelines published by the National Institute for Health and Clinical Excellence (NICE) — Depression: the treatment and management of depression in adults [National Collaborating Centre for Mental Health, 2009a; NICE, 2009a] and Depression in adults with a chronic physical health problem [National Collaborating Centre for Mental Health, 2009b; NICE, 2009b].
Compulsory admission
When is compulsory admission appropriate?
If the person needs to be admitted to hospital, every attempt should be made to persuade them to go voluntarily.
If admission is necessary but the person declines, compulsory admission may be arranged under sections 2, 3, or 4 of the Mental Health Act.
The Mental Health Act allows compulsory admission of people who:
Have a mental disorder of a nature and degree that warrants treatment in hospital, and
Need to be admitted in the interests of their own health or safety, or for the protection of other people.
Compulsory admission is arranged using the appropriate section of the Mental Health Act.
Section 2 allows compulsory admission for up to 28 days for assessment.
Section 3 allows compulsory admission for up to 6 months for treatment.
Sections 2 and 3 require an application from an Approved Mental Health Professional (AMHP, formerly an Approved Social Worker), or, rarely, the person's nearest relative, and recommendations from two doctors; one of whom is section 12 approved (usually a psychiatrist) and one who has previous acquaintance with the individual (usually the person's GP if at all practicable).
Ideally, the person should be examined jointly by the two doctors with the AMHP also present. Where this is not possible, each doctor may carry out a separate examination. If the AMHP is not present, it is essential that at least one of the doctors discusses the person with the AMHP.
Section 4 is used in exceptional cases to permit compulsory admission for up to 72 hours if there is urgent necessity, and undesirable delay would occur while trying to arrange admission under section 2.
It requires an application from an AMHP (or, rarely, the person's nearest relative) and just one medical recommendation, preferably from a doctor with previous acquaintance (usually the GP).
Section 136 may be used by police to take people from a public place to a place of safety and enable examination by a registered medical practitioner and interview by an AMHP. The person's GP, if known, may be informed.
The Mental Health Act 2007 made a number of amendments to the Mental Health Act 1983, including:
Broadening of the range of practitioners who can take on the functions formerly performed by the Approved Social Worker to include nurses, occupational therapists, and psychologists (who are now referred to as Approved Mental Health Professionals).
A requirement that young people 16 or 17 years of age who refuse admission to hospital for mental health treatment cannot be detained on the basis of their parents' consent, but will need to be formally detained under the Mental Health Act.
For admission under section 2, where there is no obvious person to provide the second medical recommendation (for example because the person is not registered with a GP or is not known to local mental health services), another section 12-approved doctor is usually asked to assess the individual. However, in cases where this is not practicable, any registered medical practitioner may provide the second recommendation as long as they do not work in the same hospital as the doctor providing the first recommendation.
Where the person has been compulsorily admitted under an emergency section 4, this section is usually converted to a section 2 (usually requiring further involvement of the GP).
Guidance and forms for the most common sections of the Mental Health Act can be accessed from the Department of Health website, as well as details of amendments made in the Mental Health Act 2007 [DH, 2007c].
Basis for recommendation
Basis for recommendation
These recommendations are based on Department of Health guidance for GPs on use of the Mental Health Act 1983 [DH, 2001], amendments made in the Mental Health Act 2007 [DH, 2007a; HMSO, 2007; DH, 2008], and a clinical review, Mental health and the law [Barker, 1997].
Psychological interventions
Which psychological interventions are available?
Cognitive behavioural therapy (CBT) is the basis of many of the psychological interventions recommended for people with depression.
The National Institute for Health and Clinical Excellence (NICE) stratifies the preferred psychological interventions into low-intensity and high-intensity, the availability of which may vary according to locality.
Improving Access to Psychological Therapies (IAPT) was introduced by the Department of Health in October 2007 and is now the major source of psychological therapy for the management of depression in England.
Low-intensity psychological interventions are suitable for people with persistent subthreshold depressive symptoms or mild depression, and include:
Individual guided self-help.
Computerized cognitive behavioural therapy (CCBT).
Structured group-based physical activity programme.
Group-based peer support.
High-intensity psychological interventions are generally reserved for people with moderate-to-severe depression, and include:
Group-based or individual CBT.
Interpersonal therapy.
Behavioural activation.
Couples therapy.
Counselling and short-term psychodynamic therapy are less preferred by NICE for the treatment of depression, due to a lack of evidence on effectiveness compared with the interventions above, but they may be appropriate for some people.
Low-intensity interventions
What are the low-intensity psychological interventions?
Low-intensity psychological interventions are cost-effective for the management of subthreshold depressive symptoms and mild depression and are preferred as initial treatment over individual and group-based cognitive behavioural therapy (CBT) and other high-intensity psychological interventions. Approaches include:
Individual guided self-help, based on the principles of CBT
Includes written materials or other media relevant to reading age.
Is facilitated by a trained practitioner who monitors progress.
Typical models consist of 6–8 sessions (face-to-face and via telephone) over 9–12 weeks.
A major element is homework, where the person needs to practice cognitive-behavioural techniques. This level of effort does not suit everybody.
Computerized CBT (CCBT)
Provided via a stand-alone computer-based or web-based programme and supported by a trained practitioner who monitors progress.
Explains the CBT model and uses thought-challenging and active monitoring of behaviour and thought patterns.
Typically takes place over 9–12 weeks, and tasks are assigned to the person between sessions.
A structured group-based physical activity programme
The most effective model is group-based sessions with support from a competent practitioner.
Typically consists of 2–3 sessions per week of moderate duration (45 minutes to 1 hour) over a 3-month period.
If the person has a comorbid chronic physical illness there should be modification according to ability, and coordination with any rehabilitation programme.
Group-based peer support
Is a self-help programme for those with a chronic physical problem, to allow sharing of experiences and feelings with a group which has an understanding of the difficulties and issues facing the individual.
It should be supported by facilitators, who have knowledge of the chronic physical health problem, and who review progress with individuals participating in the group.
Typically consists of one session per week over 8–12 weeks.
Basis for recommendation
Basis for recommendation
These recommendations are based on guidelines published by the National Institute for Health and Clinical Excellence (NICE) — Depression: the treatment and management of depression in adults [National Collaborating Centre for Mental Health, 2009a; NICE, 2009a] and Depression in adults with a chronic physical health problem [National Collaborating Centre for Mental Health, 2009b; NICE, 2009b].
Guided self-help
NICE found five studies which investigated the effects of guided self-help on depression.
Guided self-help was effective in reducing self-reported depressive symptoms when compared with waiting list controls in people with largely subthreshold depressive symptoms.
Computerized cognitive behavioural therapy (CCBT)
NICE found seven randomized trials comparing CCBT with control groups, and two further studies which made comparisons with another psychoeducation website or group-based CBT. The trials principally involved people with mild-to-moderate depression, although half had no formal diagnosis.
There were small-to-medium improvements in self-reported depression scores compared with non-active controls. Evidence was limited at follow up and disappeared at 3 months and 5 months when the mixed anxiety and depression populations were removed. No difference was apparent with the other intervention-led controls.
Structured group-based physical activity programmes
In the past, 'exercise on prescription' has been recommended for depression. Whilst recognizing that benefits have plausible mechanisms and may lead to positive feedback through an increased sense of self-worth, NICE cites difficulty in interpreting the data supporting evidence of benefit due to a 'challenging dataset'.
The data analysed covered a wide range of physical activities and mainly involved people with mild-to-moderate depression. NICE concluded that:
In the treatment of subthreshold symptoms and mild-to-moderate depression, physical activity is more effective at reducing symptoms than a placebo pill or no physical activity.
Group-based physical activity is effective in treating depression, and supervision seems to be an important factor in the effectiveness of physical activity programmes.
Group-based programmes are recommended as they are likely to be more cost-effective than individually-tailored programmes.
Choice of exercise should be based on the person's preference, as there is a lack of evidence on which to make specific recommendations regarding type of physical activity.
Group-based peer support
NICE found four studies which compared group-based peer support with standard care for people with depression and a chronic physical health problem.
There was a small but statistically significant effect on depression, but when a study which did not specifically recruit participants with depression and chronic physical health problems was excluded from the analysis, a large effect on depression was found.
High-intensity interventions
What are the high-intensity psychological interventions?
High-intensity psychological interventions are generally reserved for people with moderate-to-severe depression. Recommended approaches are cognitive behavioural therapy (CBT) or interpersonal therapy (IPT), and occasionally behavioural activation and behavioural couples therapy. CBT has the most robust evidence for effectiveness, making it the first-line psychological therapy. IPT is considered to be an appropriate alternative to CBT for moderate depression.
CBT
CBT uses techniques to help the person develop skills and strategies for identifying and counteracting problematic (negative) thoughts, beliefs, and interpretations.
Group-based CBT uses a highly structured approach with a strong psychoeducational component, based on models such as Coping with depression [Lewinsohn et al, 1984]. Group members are taught techniques and strategies to assist with coping. These strategies include improving social skills, tackling negative thinking, relaxation training, and increasing pleasant activities. A typical model would be delivered by two trained practitioners in groups of 8–10 participants with twelve 2-hour sessions over 8–12 weeks.
Individual CBT involves the person working on a one-to-one basis with the therapist. Treatment is usually given over 16–20 sessions over 3–4 months. For people with severe depression, two sessions per week might be provided for the first 2–3 weeks of treatment.
IPT
Focuses on current relationships rather than past ones, and on interpersonal processes rather than internal psychic process; it helps the person to link moods and recognize the impact on interpersonal relationships.
Duration and number of sessions is similar to CBT.
Behavioural activation
Aims to reduce symptoms and problematic behaviours through behavioural tasks related to reducing avoidance, graded exposure, activity scheduling, and initiating positively-reinforced behaviours.
Duration and number of sessions is similar to CBT.
Couples therapy
Is based on behavioural principles and can be used for people who have a regular partner and where the relationship contributes to the depression, or where involving the partner is considered to be of potential therapeutic benefit.
It typically consists of 15–20 sessions over 5–6 months.
Basis for recommendation
Basis for recommendation
These recommendations are based on guidelines published by the National Institute for Health and Clinical Excellence (NICE) — Depression: the treatment and management of depression in adults [National Collaborating Centre for Mental Health, 2009a; NICE, 2009a] and Depression in adults with a chronic physical health problem [National Collaborating Centre for Mental Health, 2009b; NICE, 2009b].
Group-based cognitive behavioural therapy (CBT)
NICE identified three studies which compared group-based CBT with other psychotherapies, with improvement in self-rated depression scores for those receiving group-based CBT. Four studies using the Coping with depression approach [Lewinsohn et al, 1984] compared group-based CBT with waiting list controls or usual treatment; there was no difference in discontinuation rates, and depression scores were lower in the group-based CBT participants at the 6-month follow up.
NICE concluded that group-based CBT was effective for people with mild depression; it was considered to be more expensive than low-intensity psychological interventions and was placed at a higher threshold on grounds of cost-minimization.
Individual CBT
Of the psychological interventions for depression, individual CBT has the most evidence for effectiveness. The largest dataset compares individual CBT with antidepressant medication, and indicates broad equivalence across the range of severities of depression.
In people with moderate or severe depression, combination treatment with CBT and an antidepressant is more effective than an antidepressant alone, and is cost-effective.
NICE no longer recommends brief CBT, as there is little evidence to support this compared with the longer durations of treatment used in most studies of individual and group-based CBT.
Interpersonal therapy (IPT)
The evidence base for IPT is smaller, weaker, and less wide-ranging than that for CBT. However, it is sufficiently convincing for IPT to be recommended as an alternative to CBT.
Behavioural activation
Evidence in favour of behavioural activation is less robust than that for CBT or IPT, so it is not recommended as a direct alternative to CBT or IPT, but can still be considered as an option.
Counselling and short-term psychodynamic therapy
What is counselling and short-term psychodynamic therapy?
These interventions are less preferred for the treatment of depression, due to a lack of evidence on effectiveness compared with other psychological interventions.
Counselling
Counselling is a generic term to describe a broad range of interventions delivered by counsellors, usually working in primary care.
Psychodynamic, systemic, or cognitive behavioural elements may be used to explore and discover ways of living more resourcefully.
Counselling might be considered for those with subthreshold depressive symptoms and mild-to-moderate depression who refuse, or do not improve with, cognitive behavioural therapy (CBT) or interpersonal therapy (IPT).
There is a lack of evidence on the effectiveness of counselling in the treatment of depression, and this should be discussed with the person when counselling is being considered.
Counselling is usually provided in 6–10 sessions over a period of 8–12 weeks.
Short-term psychodynamic psychotherapy
Is derived from a psychoanalytic model which focuses on working through conflicts originating in the past and exploring feelings. It does not teach specific skills.
It might be considered for those with mild-to-moderate depression who refuse, or do not improve with, CBT or IPT.
The limited evidence of effectiveness should be discussed with the person.
Although referred to as short term, the intervention is still typically 16–20 sessions over 4–6 months.
Basis for recommendation
Basis for recommendation
These recommendations are based on guidelines published by the National Institute for Health and Clinical Excellence (NICE) — Depression: the treatment and management of depression in adults [National Collaborating Centre for Mental Health, 2009a; NICE, 2009a] and Depression in adults with a chronic physical health problem [National Collaborating Centre for Mental Health, 2009b; NICE, 2009b].
Counselling
Evidence as to whether counselling in primary care is effective for the treatment of depression is very limited due to variations in study design and differences in approach.
NICE has downgraded its recommendation for counselling in the light of the increased evidence favouring the low-intensity psychological interventions and group-based cognitive behavioural therapy for the treatment of mild depression.
Short-term psychodynamic psychotherapy
Effectiveness in treating depression is uncertain as the evidence base is weak.
It has not been possible to demonstrate consistent benefit over waiting list or usual care.
Choice of antidepressant
Which antidepressant should I prescribe?
When starting any antidepressant, warn the person of the potential for an initial increase in agitation, anxiety, and suicidal ideation.
Although a number of factors may influence the choice of antidepressant, in general:
If this is a first episode of depression, consider:
Prescribing a generic selective serotonin reuptake inhibitor (SSRI), such as citalopram, fluoxetine, paroxetine, or sertraline.
If this is a recurrent episode of depression, consider:
Prescribing an antidepressant that the person has had a good response to previously.
Avoiding antidepressants that the person has previously failed to respond to or could not tolerate.
If the person has a chronic physical health problem:
Sertraline may be preferred, because it has a lower risk of drug interactions.
If an SSRI is prescribed, consider gastroprotection in older people who are taking nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin.
For a brief summary on which antidepressants may be prescribed for people with chronic physical health problems, see Chronic physical health problems. For more detailed information, see appendix 16 of the full NICE guideline.
For information regarding the choice of antidepressant in women who are pregnant or breastfeeding, see the CKS topic on Depression - antenatal and postnatal.
Additional information
Factors influencing the choice of an antidepressant
Other factors to consider when choosing an antidepressant include:
The person's preference.
Adverse effect profile — for example, sedation, sexual adverse effects, weight gain.
Toxicity in overdose — avoid tricyclic antidepressants or venlafaxine if there is a history, or likelihood, of overdose.
Other drug treatments that may interact with the antidepressant drugs.
Associated psychiatric disorder that may specifically respond to a particular class of antidepressant — for example, obsessive compulsive disorder and selective serotonin reuptake inhibitors (SSRIs).
Basis for recommendation
Basis for recommendation
These recommendations are based on guidelines published by the National Institute for Health and Clinical Excellence (NICE) — Depression: the treatment and management of depression in adults [National Collaborating Centre for Mental Health, 2009a; NICE, 2009a] and Depression in adults with a chronic physical health problem [National Collaborating Centre for Mental Health, 2009b; NICE, 2009b], and published expert opinion [Anderson et al, 2008].
NICE concluded that the efficacy of the different antidepressants is largely equivalent.
NICE found no evidence that newer antidepressants such as escitalopram, duloxetine, or venlafaxine are more effective than other antidepressants. The choice of antidepressant should depend on adverse effect profiles, the person's preference, previous experience of treatments, likelihood to cause discontinuation symptoms, and safety in overdose.
NICE states that because an increasing number of newer antidepressants are available as generics, these are generally preferred on grounds of cost.
NICE recommends using a generic selective serotonin reuptake inhibitor (SSRI) because they have a better adverse effect profile than other antidepressants and are less toxic in overdose.
NICE recommends that citalopram and sertraline may be preferred in people with a chronic physical health problem because they have a lower propensity for drug interactions [NICE, 2009b].
However citalopram and escitalopram have been found to prolong the QT interval and are now contraindicated in people who are already taking medication known to prolong the QT interval as there may be an additive effect [Lundbeck Ltd, 2011a; Lundbeck Ltd, 2011b; MHRA, 2011]. Caution is advised in people with congenital long QT interval or who have pre-existing QT interval prolongation as they have a higher risk than average of developing a ventricular arrhythmia including Torsade de Pointes.
CKS therefore recommends sertraline as the preferred antidepressant for people with a chronic physical health problem.
Advice about driving
What advice should I give about driving?
For depression without significant memory or concentration problems, agitation, behavioural disturbance, or suicidal thoughts, the DVLA's medical rules are:
For group 1 entitlement (cars, motorcycles):
The DVLA need not be notified and driving may continue.
However, all antidepressants (and particularly tricyclic antidepressants) can impair alertness, concentration and driving performance. This is particularly so at the start of treatment, or soon after, and when dosage is being increased. Driving must cease if adversely affected.
For group 2 entitlement (lorries, buses):
Very minor short-lived illnesses need not be notified to the DVLA.
However, the choice of antidepressant for a professional driver should take into account the adverse effects which impair driving. Driving must cease if adversely affected.
For depression with significant memory or concentration problems, agitation, behavioural disturbance, or suicidal thoughts, the DVLA's medical rules are:
For group 1 entitlement (cars, motorcycles):
Driving should cease pending the outcome of medical enquiry.
A period of stability depending upon the circumstances will be required before driving can be resumed. Particularly dangerous are those who may attempt suicide at the wheel.
For group 2 entitlement (lorries, buses):
Driving should cease pending the outcome of medical enquiry.
Driving may be permitted when the person is well and stable for a period of 6 months.
Medication must not cause side effects which would interfere with alertness or concentrations.
Driving is usually permitted if the anxiety or depression is long-standing, but maintained symptom-free on doses of psychotropic medication which do not impair.
The DVLA may require psychiatric reports.
Advise the person that it is their responsibility to inform the Driver and Vehicle Licensing Agency (DVLA) of any condition that may affect their ability to drive.
The person should check with their insurer that they are still covered for driving.
The latest information from the DVLA regarding medical fitness to drive can be obtained at www.dvla.gov.uk/medical/ataglance.
Basis for recommendation
Basis for recommendation
This information on medical rules is from the Driver and Vehicle Licensing Agency's guidance for medical practitioners, At a glance guide to the current medical standards of fitness to drive [DVLA, 2010].
Scenario: Ongoing management
Scenario: Ongoing management of depression
Assessment at review
How should I assess someone at review?
Follow general principles of care.
Reassess criteria for referral or admission.
In particular, be alert to suicidal ideation (see Assessing risk of suicide).
If the person is considered to be at risk of suicide, see Managing a person at risk of suicide.
Consider using depression questionnaires to monitor progress.
Check adherence to treatment and enquire about adverse effects.
Re-evaluate the frequency of contact based on:
The person's preference.
Risk factors for relapse.
Comorbid conditions.
Change since last review and response to interventions.
Symptoms during treatment changes (such as agitation, anxiety, and suicidal ideation).
Severity and frequency of previous episodes of depression.
If suicide is not considered to be a risk:
Review at 2 weeks.
Then review regularly, perhaps every 2–4 weeks for the first 3 months.
If the response at 4 weeks is poor, consider changing management.
If the response is good, longer review intervals can be considered.
At 6 months after remission, the duration of medication is reviewed depending on the risk of relapse.
Basis for recommendation
Basis for recommendation
These recommendations are based on guidelines published by the National Institute for Health and Clinical Excellence (NICE) — Depression: the treatment and management of depression in adults [National Collaborating Centre for Mental Health, 2009a; NICE, 2009a] and Depression in adults with a chronic physical health problem [National Collaborating Centre for Mental Health, 2009b; NICE, 2009b].
Partial or no response to treatment
How should I manage someone if there is a partial or no response to treatment?
For people with subthreshold depressive symptoms or mild-to-moderate depression who are being actively monitored:
If the person is still unwell after 2 weeks, consider offering a low-intensity psychological intervention or, if this is declined, group-based cognitive behavioural therapy.
If the person is failing to respond to a low-intensity psychological intervention, discuss the relative merits of different interventions and consider offering:
An antidepressant, or
A high-intensity psychological intervention.
If the person is already taking an antidepressant, see below.
For people with moderate or severe depression who have not responded to initial measures:
If the person is already taking an antidepressant, see below.
Consider combination therapy with an antidepressant and a high-intensity psychological intervention.
If the depression is complex and severe, refer to specialist services.
If the person is taking an antidepressant:
At any stage of treatment, the antidepressant can be stopped if the person has unacceptable adverse effects or if the person prefers.
If anxiety, agitation, or insomnia are problematic, consider short-term (usually less than 2 weeks) concomitant treatment with a benzodiazepine.
If there is no improvement within 2–4 weeks of starting an antidepressant, check adherence and enquire about adverse effects.
If response is absent or minimal after 3–4 weeks of treatment with a therapeutic dose of an antidepressant:
Consider increasing the dose in line with product recommendations (if there are no significant adverse effects), or
Consider switching to a different antidepressant (if there are adverse effects or if the person prefers).
If there is some response by 4 weeks:
Continue the antidepressant for another 2–4 weeks and check for adequate response.
Maintain a low threshold for considering switching to a different antidepressant if response is not adequate at 6–8 weeks, or if there are adverse effects, or if the person prefers.
If there is also a chronic physical health problem, consider referral for collaborative care which should normally include:
Case management supervised by a dedicated coordinator and support from a senior mental health professional.
Close collaboration between primary and secondary care physical health services and specialist mental health services.
A range of psychological and drug interventions.
Long-term coordination of care and follow up.
Basis for recommendation
Basis for recommendation
These recommendations are based on guidelines published by the National Institute for Health and Clinical Excellence (NICE) — Depression: the treatment and management of depression in adults [National Collaborating Centre for Mental Health, 2009a; NICE, 2009a] and Depression in adults with a chronic physical health problem [National Collaborating Centre for Mental Health, 2009b; NICE, 2009b].
The recommendations are supported by randomized controlled trials of moderate or high quality.
Collaborative care:
NICE found a reasonable evidence base to support the use of collaborative care in people with moderate-to-severe depression and a chronic physical health problem.
Evidence regarding the effects on physical health is more limited and requires more research but any reductions in the burden on medical services are likely to offset the costs of the interventions.
NICE recommends the approach as being of particular value for those with a chronic physical health problem with associated functional impairment whose depression has not responded to initial high-intensity psychological interventions, pharmacological treatment, or a combination thereof.
Collaborative care can be provided at the primary or secondary care level and involves all sectors of mental and physical healthcare which are coordinated by a dedicated person with support from a multi-professional team. Determination of the care plan is done jointly and long-term follow up is planned.
Responding to treatment; preventing relapse
How should I manage someone who is responding, and how can I prevent relapse?
Support and encourage people who are improving.
If the person is taking an antidepressant:
Continue this for at least 6 months following remission (and perhaps up to 12 months in older adults), and inform the person that this greatly reduces the risk of relapse.
Check adherence and enquire about adverse effects.
Base the duration of maintenance treatment on the assessed risk of relapse, taking into account:
The number and pattern of previous episodes.
Residual symptoms.
Concurrent physical health problems and psychosocial difficulties.
Choose longer maintenance periods:
When there are multiple risk factors.
If consequences of relapse are likely to be severe (such as suicide or job loss).
If there were two or more episodes of major depression with significant functional deficit in the recent past.
If the risk of relapse is significant:
Advise the use of antidepressants for at least 2 years, maintained at the effective treatment dose (unless there is a good reason to reduce the dose).
Continue maintenance treatment beyond 2 years based on a risk assessment.
Consider whether the person would benefit from one of the recommended psychological interventions for relapse prevention.
Individual cognitive behavioural therapy.
Mindfulness-based cognitive therapy.
If additional social support is needed, consider:
Befriending (where trained volunteers provide at least weekly contact for 2–6 months).
A rehabilitation programme (particularly if there has been long-term loss of work or social disengagement).
Basis for recommendation
Basis for recommendation
These recommendations are based on guidelines published by the National Institute for Health and Clinical Excellence (NICE) — Depression: the treatment and management of depression in adults [National Collaborating Centre for Mental Health, 2009a; NICE, 2009a] and Depression in adults with a chronic physical health problem [National Collaborating Centre for Mental Health, 2009b; NICE, 2009b].
Referral or seeking specialist advice
When should I refer or seek specialist advice?
If the person has taken an overdose, see the CKS topic on Poisoning or overdose.
Refer with appropriate urgency to a specialist mental health service if the person:
Is actively suicidal or has a current suicide plan, or is at significant risk of self-harm.
Presents with considerable immediate risk to themselves or others.
Also consider urgent referral if the person has:
Psychotic symptoms (hallucinations, delusions).
Severe agitation accompanying severe symptoms.
Evidence of severe self-neglect.
Deteriorating personal circumstances exacerbating their mental illness.
If admission is thought to be necessary but the person refuses, see Crisis intervention and Compulsory admission.
Consider consulting with, or referring to, a practitioner with a special interest in treating depression or to a specialist service for any of the following:
Unclear diagnosis.
Failure to respond to two or more interventions.
Recurrent episode of depression within 1 year of the last one.
History suggestive of bipolar disorder.
More persistent suicidal thoughts.
Comorbid substance, physical, or sexual abuse.
Severe psychosocial problems.
Deteriorates quickly.
Cognitive impairment.
Referral is requested by the person with depression or their carers.
Crisis intervention
Crisis intervention
Crisis plans identify potential triggers and strategies to manage them. They should be shared with the GP and others relevant to the person's care.
Crisis resolution and home treatment teams (CRHTTs) may be an alternative to hospital admission, offering intensive home-based support in cases where this is considered to be the most appropriate setting.
CRHTTs may also facilitate early discharge from hospital; however, much of the data pertaining to their use refers to schizophrenia.
While there is insufficient evidence to clearly support their use in depression, the National Institute for Health and Clinical Excellence (NICE) advises that crisis teams may have a role for a small number of people with depression who require more intensive care.
Basis for recommendation
Basis for recommendation
These recommendations are based on guidelines published by the National Institute for Health and Clinical Excellence (NICE) — Depression: the treatment and management of depression in adults [National Collaborating Centre for Mental Health, 2009a; NICE, 2009a] and Depression in adults with a chronic physical health problem [National Collaborating Centre for Mental Health, 2009b; NICE, 2009b].
NICE found insufficient evidence from randomized controlled trials to determine the value of crisis resolution and home treatment teams for people with depression but based the general recommendation on expert opinion.
Specialist services can offer:
Further drug treatments.
High-intensity psychological interventions.
Combined and augmented treatments.
Access to a crisis service.
Inpatient care and electro-convulsive therapy.
Managing a person at risk of suicide
How do I respond to the risk of suicide?
If the person with depression is assessed to be at considerable immediate risk to themselves or others:
Refer with appropriate urgency to a specialist mental health service.
If admission is thought to be necessary but the person refuses, see Compulsory admission.
If the person has suicidal ideation:
Consider the toxicity of the prescribed medication and the quantities issued.
Consider the adequacy of, and access to, further support.
Advise on what to do if the situation deteriorates.
Consider referral to a specialist service.
General measures
Do not offer false reassurance; rather, aim to problem-solve.
Ensure the person is aware of potential sources of help and a point of contact for an appropriate healthcare professional.
Advise the person, as well as their family and carers, to seek help if the situation deteriorates.
Advise family members and carers to be vigilant for suicidal ideation.
Advise the person's family and carers to be aware of high-risk periods (such as when starting treatment, changes in treatment, increased personal stress) and to be vigilant for changes in mood, such as increased negativity, hopelessness, and suicidal intent.
Careful follow up
Ensure all episodes have adequate follow up. There is no such thing as a minor overdose.
Consider whether increased support is needed, such as more frequent contact (direct or telephone).
People with depression started on antidepressants who are considered to be at risk of suicide or who are younger than 30 years of age should normally be seen after 1 week, then as frequently as needed until the risk is no longer considered clinically important.
In cases of concern, use clinical judgement; an earlier review may be more appropriate.
Basis for recommendation
Basis for recommendation
These recommendations are based on guidelines published by the National Institute for Health and Clinical Excellence (NICE) — Depression: the treatment and management of depression in adults [National Collaborating Centre for Mental Health, 2009a; NICE, 2009a] and Depression in adults with a chronic physical health problem [National Collaborating Centre for Mental Health, 2009b; NICE, 2009b].
Compulsory admission
When is compulsory admission appropriate?
If the person needs to be admitted to hospital, every attempt should be made to persuade them to go voluntarily.
If admission is necessary but the person declines, compulsory admission may be arranged under sections 2, 3, or 4 of the Mental Health Act.
The Mental Health Act allows compulsory admission of people who:
Have a mental disorder of a nature and degree that warrants treatment in hospital, and
Need to be admitted in the interests of their own health or safety, or for the protection of other people.
Compulsory admission is arranged using the appropriate section of the Mental Health Act.
Section 2 allows compulsory admission for up to 28 days for assessment.
Section 3 allows compulsory admission for up to 6 months for treatment.
Sections 2 and 3 require an application from an Approved Mental Health Professional (AMHP, formerly an Approved Social Worker), or rarely, the person's nearest relative, and recommendations from two doctors; one of whom is section 12-approved (usually a psychiatrist) and one who has previous acquaintance with the individual (usually the person's GP if at all practicable).
Ideally, the person should be examined jointly by the two doctors with the AMHP also present. Where this is not possible, each doctor may carry out a separate examination. If the AMHP is not present, it is essential that at least one of the doctors discusses the person with the AMHP.
Section 4 is used in exceptional cases to permit compulsory admission for up to 72 hours if there is urgent necessity, and undesirable delay would occur while trying to arrange admission under section 2.
It requires an application from an AMHP (or, rarely, the person's nearest relative) and just one medical recommendation, preferably from a doctor with previous acquaintance (usually the GP).
Section 136 may be used by police to take people from a public place to a place of safety and enable examination by a registered medical practitioner and interview by an AMHP. The person's GP, where known, may be informed.
The Mental Health Act 2007 made a number of amendments to the Mental Health Act 1983, including:
Broadening of the range of practitioners who can take on the functions formerly performed by the Approved Social Worker to include nurses, occupational therapists, and psychologists (who are now referred to as Approved Mental Health Professionals).
A requirement that young people 16 or 17 years of age who refuse admission to hospital for mental health treatment cannot be detained on the basis of their parents' consent, but will need to be formally detained under the Mental Health Act.
For admission under section 2, where there is no obvious person to provide the second medical recommendation (for example because the person is not registered with a GP or is not known to local mental health services), another section 12-approved doctor is usually asked to assess the individual. However, in cases where this is not practicable, any registered medical practitioner may provide the second recommendation as long as they do not work in the same hospital as the doctor providing the first recommendation.
Where the person has been compulsorily admitted under an emergency section 4, this section is usually converted to a section 2 (usually requiring further involvement of the GP).
Guidance and forms for the most common sections of the Mental Health Act can be accessed from the Department of Health website (www.dh.gov.uk), as well as details of amendments made in the Mental Health Act 2007 [DH, 2007c].
Basis for recommendation
Basis for recommendation
These recommendations are based on Department of Health guidance for GPs on use of the Mental Health Act 1983 [DH, 2001], amendments made in the Mental Health Act 2007 [DH, 2007a; HMSO, 2007; DH, 2008], and a clinical review, Mental health and the law [Barker, 1997].
Psychological interventions
Which psychological interventions are available?
Cognitive behavioural therapy (CBT) is the basis of many of the psychological interventions recommended for people with depression.
The National Institute for Health and Clinical Excellence (NICE) stratifies the preferred psychological interventions into low-intensity and high-intensity, the availability of which may vary according to locality.
Low-intensity psychological interventions are suitable for people with subthreshold depressive symptoms or mild depression, and include:
Individual guided self-help.
Computerized cognitive behavioural therapy (CCBT).
Structured group-based physical activity programme.
Group-based peer support.
High-intensity psychological interventions are generally reserved for people with moderate-to-severe depression, and include:
Group-based or individual CBT.
Interpersonal therapy.
Behavioural activation.
Couples therapy.
Counselling and short-term psychodynamic therapy are less preferred by NICE for the treatment of depression, due to a lack of evidence on effectiveness compared with the interventions above, but they may be appropriate for some people.
Interventions for relapse prevention include:
Individual CBT.
Mindfulness-based cognitive therapy.
Low-intensity interventions
What are the low-intensity psychological interventions?
Low-intensity psychological interventions are cost-effective for the management of subthreshold depressive symptoms and mild depression and are preferred as initial treatment over individual and group-based cognitive behavioural therapy (CBT) and other high-intensity psychological interventions. Approaches include:
Individual guided self-help, based on the principles of CBT
Includes written materials or other media relevant to reading age.
Is facilitated by a trained practitioner who monitors progress.
Typical models consist of 6–8 sessions (face-to-face and via telephone) over 9–12 weeks.
A major element is homework, where the person needs to practice cognitive-behavioural techniques. This level of effort does not suit everybody.
Computerized CBT (CCBT)
Provided via a stand-alone computer-based or web-based programme and supported by a trained practitioner who monitors progress.
Explains the CBT model and uses thought-challenging and active monitoring of behaviour and thought patterns.
Typically takes place over 9–12 weeks, and tasks are assigned to the person between sessions.
A structured group-based physical activity programme
The most effective model is group sessions with support from a competent practitioner.
Typically consists of 2–3 sessions per week of moderate duration (45 minutes to 1 hour) over a 3-month period.
If the person has comorbid chronic physical illness there should be modification according to ability, and coordination with any rehabilitation programme.
Group-based peer support
Is a self-help programme for those with a chronic physical problem, to allow sharing of experiences and feelings with a group which has an understanding of the difficulties and issues facing the individual.
It should be supported by facilitators, who have knowledge of the chronic physical health problem, and who review progress with individuals participating in the group.
Typically consists of one session per week over 8–12 weeks.
Basis for recommendation
Basis for recommendation
These recommendations are based on guidelines published by the National Institute for Health and Clinical Excellence (NICE) — Depression: the treatment and management of depression in adults [National Collaborating Centre for Mental Health, 2009a; NICE, 2009a] and Depression in adults with a chronic physical health problem [National Collaborating Centre for Mental Health, 2009b; NICE, 2009b].
Guided self-help
NICE found five studies which investigated the effects of guided self-help on depression.
Guided self-help was effective in reducing self-reported depressive symptoms when compared to waiting-list controls in people with largely subthreshold depressive symptoms.
Computerized cognitive behavioural therapy (CCBT)
NICE found seven randomized trials comparing CCBT with control groups, and two further studies which made comparisons with another psychoeducation website or group CBT. The trials principally involved people with mild-to-moderate depression, although half had no formal diagnosis.
There were small-to-medium improvements in self-reported depression scores compared with non-active control. Evidence was limited at follow up and disappeared at 3 months and 5 months when the mixed anxiety and depression populations were removed. No difference was apparent with the other intervention-led controls.
Structured group-based physical activity programmes
In the past, 'exercise on prescription' has been recommended for depression. Whilst recognizing that benefits have plausible mechanisms and may lead to positive feedback through an increased sense of self-worth, NICE cites difficulty in interpreting the data supporting evidence of benefit due to a 'challenging dataset'.
The data analysed covered a wide range of physical activities and mainly involved people with mild-to-moderate depression. NICE concluded that:
In the treatment of subthreshold symptoms and mild-to-moderate depression, physical activity is more effective at reducing symptoms than placebo pill or no physical activity.
Group-based physical activity is effective in treating depression, and supervision seems to be an important factor in the effectiveness of physical activity programmes.
Group programmes are recommended as they are likely to be more cost-effective than individually-tailored programmes.
Choice of exercise should be based on the person's preference, as there is a lack of evidence on which to make specific recommendations regarding type of physical activity.
Group-based peer support
NICE found four studies which compared group-based peer support with standard care for people with depression and a chronic physical health problem.
There was a small but statistically significant effect on depression. However, when a study which did not specifically recruit participants with depression and chronic physical health problems was excluded from the analysis, a large effect on depression was found.
High-intensity interventions
What are the high-intensity psychological interventions?
High-intensity psychological interventions are generally reserved for people with moderate-to-severe depression. Recommended approaches are cognitive behavioural therapy (CBT) or interpersonal therapy (IPT), and occasionally behavioural activation and behavioural couples therapy. CBT has the most robust evidence for effectiveness, making it the first-line psychological therapy. IPT is considered to be an appropriate alternative to CBT for moderate depression.
CBT
CBT uses techniques to help the person develop skills and strategies for identifying and counteracting problematic (negative) thoughts, beliefs, and interpretations.
Group-based CBT uses a highly structured approach with a strong psychoeducational component, based on models such as Coping with depression [Lewinsohn et al, 1984]. Group members are taught techniques and strategies to assist with coping. These strategies include improving social skills, tackling negative thinking, relaxation training, and increasing pleasant activities. A typical model would be delivered by two trained practitioners in groups of 8–10 participants with twelve 2-hour sessions over 8–12 weeks.
Individual CBT involves the person working on a one-to-one basis with the therapist. Treatment is usually given over 16–20 sessions over 3–4 months. For people with severe depression, two sessions per week might be provided for the first 2–3 weeks of treatment.
IPT
Focuses on current relationships rather than past ones, and on interpersonal processes rather than internal psychic process; it helps the person to link moods and recognize the impact on interpersonal relationships.
Duration and number of sessions is similar to CBT.
Behavioural activation
Aims to reduce symptoms and problematic behaviours through behavioural tasks related to reducing avoidance, graded exposure, activity scheduling, and initiating positively-reinforced behaviours.
Duration and number of sessions is similar to CBT.
Couples therapy
Is based on behavioural principles and can be used for people who have a regular partner and where the relationship contributes to the depression, or where involving the partner is considered to be of potential therapeutic benefit.
It typically consists of 15–20 sessions over 5–6 months.
Basis for recommendation
Basis for recommendation
These recommendations are based on guidelines published by the National Institute for Health and Clinical Excellence (NICE) — Depression: the treatment and management of depression in adults [National Collaborating Centre for Mental Health, 2009a; NICE, 2009a] and Depression in adults with a chronic physical health problem [National Collaborating Centre for Mental Health, 2009b; NICE, 2009b].
Group-based cognitive behavioural therapy (CBT)
NICE identified three studies which compared group-based CBT with other psychotherapies, with improvement in self-rated depression scores for those receiving group-based CBT. Four studies using the Coping with depression approach [Lewinsohn et al, 1984] compared group-based CBT with waiting-list controls or usual treatment; there was no difference in discontinuation rates, and depression scores were lower in the group-based CBT participants at the 6-month follow up.
NICE concluded that group-based CBT was effective for people with mild depression; it was considered to be more expensive than low-intensity psychological interventions and was placed at a higher threshold on grounds of cost-minimization.
Individual CBT
Of the psychological interventions for depression, individual CBT has the most evidence for effectiveness. The largest dataset compares individual CBT with antidepressant medication, and indicates broad equivalence across the range of severities of depression.
In people with moderate or severe depression, combination treatment with CBT and an antidepressant is more effective than an antidepressant alone, and is cost-effective.
NICE no longer recommends 'brief CBT', as there is little evidence to support this compared with the longer durations of treatment used in most studies of individual and group-based CBT.
Interpersonal therapy (IPT)
The evidence base for IPT is smaller, weaker, and less wide-ranging than that for CBT. However, it is sufficiently convincing for IPT to be recommended as an alternative to CBT.
Behavioural activation
Evidence in favour of behavioural activation is less robust than that for CBT or IPT, so it is not recommended as a direct alternative to CBT or IPT, but can still be considered as an option.
Counselling and short-term psychodynamic therapy
What is counselling and short-term psychodynamic therapy?
These interventions are less preferred for the treatment of depression, due to a lack of evidence on effectiveness compared with other psychological interventions.
Counselling
Counselling is a generic term used to describe a broad range of interventions delivered by counsellors, usually working in primary care.
Psychodynamic, systemic, or cognitive behavioural elements may be used to explore and discover ways of living more resourcefully.
Counselling might be considered for those with subthreshold depressive symptoms and mild-to-moderate depression who refuse, or do not improve with, CBT or IPT.
There is a lack of evidence on the effectiveness of counselling in the treatment of depression, and this should be discussed with the person when counselling is being considered.
Counselling is usually provided in 6–10 sessions over a period of 8–12 weeks.
Short-term psychodynamic psychotherapy
Is derived from a psychoanalytic model which focuses on working through conflicts originating in the past and exploring feelings. It does not teach specific skills.
It might be considered for those with mild-to-moderate depression who refuse, or do not improve with, CBT or IPT.
The limited evidence of effectiveness should be discussed with the person.
Although referred to as short-term, the intervention is still typically 16–20 sessions over 4–6 months.
Basis for recommendation
Basis for recommendation
These recommendations are based on guidelines published by the National Institute for Health and Clinical Excellence (NICE) — Depression: the treatment and management of depression in adults [National Collaborating Centre for Mental Health, 2009a; NICE, 2009a] and Depression in adults with a chronic physical health problem [National Collaborating Centre for Mental Health, 2009b; NICE, 2009b].
Counselling
Evidence as to whether counselling in primary care is effective for the treatment of depression is very limited due to variations in study design and differences in approach.
NICE has downgraded its recommendation for counselling in the light of the increased evidence favouring the low-intensity psychological interventions and group-based cognitive behavioural therapy for the treatment of mild depression.
Short-term psychodynamic psychotherapy
Effectiveness in treating depression is uncertain as the evidence base is weak.
It has not been possible to demonstrate consistent benefit over waiting list or usual care.
Interventions for relapse prevention
What psychological interventions are recommended for relapse prevention?
Recommended approaches include individual cognitive behavioural therapy (CBT) and mindfulness-based cognitive therapy.
Individual CBT
For people who have relapsed despite antidepressant medication and for people with a significant history of depression and residual symptoms despite treatment.
Mindfulness-based cognitive therapy
For people who are currently well but have experienced three or more previous episodes of depression.
This is a group-based skills training programme that enables people to learn to recognize early warning signs in terms of negative bodily sensations, thoughts, and feelings, and to develop constructive responses that prevent relapse and avoid automatic reinstatement of damaging modes of thinking.
Typical delivery is an 8-week group programme in groups of 8–15 participants per group with 2-hour sessions and four follow-up sessions later in the year after the end of therapy.
Basis for recommendation
Basis for recommendation
These recommendations are based on guidelines published by the National Institute for Health and Clinical Excellence (NICE) — Depression: the treatment and management of depression in adults [National Collaborating Centre for Mental Health, 2009a; NICE, 2009a] and Depression in adults with a chronic physical health problem [National Collaborating Centre for Mental Health, 2009b; NICE, 2009b].
Individual cognitive behavioural therapy (CBT)
Individual CBT is recommended by NICE as one option in relapse prevention. Two studies reported a significant difference in relapse rates favouring individual CBT when compared with clinical management with antidepressants.
Mindfulness-based cognitive therapy
NICE found evidence showing lower depression scores on follow up and a reduced risk of relapse with this type of CBT approach.
Of the treatments specifically designed to reduce relapse, group-based mindfulness-based cognitive therapy has the strongest evidence base.
Antidepressant choice if initial treatment fails
Which antidepressant should I prescribe if initial treatment fails?
If the person is not already taking an antidepressant, see Choice of antidepressant in the section on New or initial management.
If the person is taking an antidepressant, but with only partial or no response, consider:
Increasing the dose in line with product recommendations (if there are no significant adverse effects) — allow adequate time for the increased dose to work, or
Switching antidepressants to a selective serotonin reuptake inhibitor (SSRI) if the person is not already taking one, or to a different SSRI.
Switching antidepressants to a different class of antidepressant; for example if an SSRI has been used initially, switch to a tricyclic antidepressant (TCA) such as amitriptyline. Other reasonable choices include lofepramine, trazodone, and venlafaxine.
When switching antidepressants, consider any comorbid conditions or potential drug interactions that may influence choice of drug (see Chronic physical health problems).
Other important factors to consider when choosing an antidepressant include:
The person's preference.
Adverse effect profile — for example sedation, sexual adverse effects, weight gain.
Toxicity in overdose — if there is a history or likelihood of overdose, avoid venlafaxine and TCAs.
Associated psychiatric disorder that may specifically respond to a particular class of antidepressant — for example obsessive compulsive disorder and SSRIs.
For information regarding the choice of antidepressant in women who are pregnant or breastfeeding, see the CKS topic on Depression - antenatal and postnatal.
Basis for recommendation
Basis for recommendation
These recommendations are based on guidelines published by the National Institute for Health and Clinical Excellence (NICE) — Depression: the treatment and management of depression in adults [National Collaborating Centre for Mental Health, 2009a; NICE, 2009a] and Depression in adults with a chronic physical health problem [National Collaborating Centre for Mental Health, 2009b; NICE, 2009b], and the Maudsley hospital guidelines [Taylor et al, 2009].
NICE concluded that the efficacy of the different antidepressants is largely equivalent. NICE found no evidence that newer antidepressants such as escitalopram, duloxetine, or venlafaxine are more effective than other antidepressants. The choice of antidepressant should depend on adverse effect profile, the person's preference, their previous experience of treatments, the likelihood of causing discontinuation symptoms, and its safety in overdose.
NICE states that because an increasing number of newer antidepressants are available as generics, these are generally preferred on grounds of cost.
NICE recommends using a generic serotonin reuptake inhibitor (SSRI) because they have a better adverse effect profile than other antidepressants and are less toxic in overdose.
Basis for increasing the dose of an antidepressant
NICE states that the evidence for increasing the dose of an antidepressant (if the person has not responded adequately to a standard dose) is not convincing. However, it concludes that overall this strategy may be effective in some people, especially if they have been able to tolerate the antidepressant at the initial dose.
Basis for switching to a different antidepressant
NICE states that the evidence for switching from one antidepressant to another is stronger than that for increasing the dose of the antidepressant. However, the evidence for switching between classes is not stronger than the evidence for increasing the dose.
NICE concludes that, overall, switching is worthwhile.
NICE states that because the evidence for changing to another antidepressant is weak, the choice of antidepressant should be guided by similar principles to that of choosing an initial antidepressant (for example adverse effect profile, drug interactions, the person's preference).
Advice about driving
What advice should I give about driving?
For depression without significant memory or concentration problems, agitation, behavioural disturbance, or suicidal thoughts, the DVLA's medical rules are:
For group 1 entitlement (cars, motorcycles):
The DVLA need not be notified and driving may continue.
However, all antidepressants (and particularly tricyclic antidepressants) can impair alertness, concentration and driving performance. This is particularly so at the start of treatment, or soon after, and when dosage is being increased. Driving must cease if adversely affected.
For group 2 entitlement (lorries, buses):
Very minor short-lived illnesses need not be notified to the DVLA.
However, the choice of antidepressant for a professional driver should take into account the adverse effects which impair driving. Driving must cease if adversely affected.
For depression with significant memory or concentration problems, agitation, behavioural disturbance, or suicidal thoughts, the DVLA's medical rules are:
For group 1 entitlement (cars, motorcycles):
Driving should cease pending the outcome of medical enquiry.
A period of stability depending upon the circumstances will be required before driving can be resumed. Particularly dangerous are those who may attempt suicide at the wheel.
For group 2 entitlement (lorries, buses):
Driving should cease pending the outcome of medical enquiry.
Driving may be permitted when the person is well and stable for a period of 6 months.
Medication must not cause side effects which would interfere with alertness or concentrations.
Driving is usually permitted if the anxiety or depression is long-standing, but maintained symptom-free on doses of psychotropic medication which do not impair.
The DVLA may require psychiatric reports.
Advise the person that it is their responsibility to inform the Driver and Vehicle Licensing Agency (DVLA) of any condition that may affect their ability to drive.
The person should check with their insurer that they are still covered for driving.
The latest information from the DVLA regarding medical fitness to drive can be obtained at www.dvla.gov.uk/medical/ataglance.
Basis for recommendation
Basis for recommendation
This information on medical rules is from the Driver and Vehicle Licensing Agency's guidance for medical practitioners, At a glance guide to the current medical standards of fitness to drive [DVLA, 2010].
Scenario: Seasonal affective disorder
Scenario: Seasonal affective disorder
Management
How should I manage someone with seasonal affective disorder?
Assess the severity of the depression and manage as for other people with depression, with psychological interventions and/or antidepressants. For more information see:
Managing a new or first presentation of depression.
Ongoing management of depression.
If the person wishes to try light therapy, advise that:
The effectiveness of light therapy is uncertain.
Light therapy is administered by a light box, dawn simulators, or incandescent light visors.
These devices cannot be prescribed on the NHS but can be purchased online or from the high street. Light treatments cost approximately £200.
A minimum dose of 5000 lux-hours per day of bright light treatment, administered in the morning during the winter months, is the most common treatment strategy.
Mild agitation is the most common adverse effect seen with light therapy.
Basis for recommendation
Basis for recommendation
These recommendations are based on guidelines published by the National Institute for Health and Clinical Excellence (NICE) — Depression: the treatment and management of depression in adults [National Collaborating Centre for Mental Health, 2009a; NICE, 2009a].
NICE recommends that treatment strategies for depression with a seasonal pattern should be the same as those for depression, because there is no convincing evidence to support different treatment strategies.
Antidepressants
NICE included six randomized controlled trials (RCTs) that assessed the effectiveness of antidepressants for the treatment of depression which had a seasonal pattern. There was no good evidence that antidepressants were effective once the person's symptoms had started, but there was some evidence that antidepressants were effective at preventing depression if they were started before symptoms began and were continued until early spring.
Psychological treatments
NICE identified no RCTs assessing the effectiveness of psychological treatments compared with placebo or antidepressants for depression with a seasonal pattern.
Light therapy for winter depression
NICE included 20 RCTs that assessed the effectiveness of light therapy for treating winter depression with a seasonal pattern. They concluded that there was very little evidence to support the use of bright light therapy. The trials were difficult to interpret as there was significant heterogeneity between them and there were a number of methodological weaknesses.
When reviewing the evidence for light therapy, the NICE guideline development group regarded treatment with a light box with 5000 lux-hours per day as a reasonable minimum dose of light therapy, with a minimum trial duration of 1 week.
Scenario: Bereavement
Scenario: Bereavement
Management
How should I manage someone with depression associated with bereavement?
Assess the bereaved person for symptoms of depression.
It may be difficult to distinguish normal grief from depressive illness. Uncomplicated bereavement and major depression share many symptoms, but active suicidal thoughts, psychotic symptoms, and profound guilt are rare with normal bereavement.
For more information on how to distinguish grief from depression, see Table 1.
If the person is symptomatic and the bereavement is recent (within the last 2 months), antidepressant use is usually inappropriate.
Consider referral to bereavement support agencies, such as Cruse Bereavement Care (www.crusebereavementcare.org.uk).
If the person is symptomatic and it is 2 months after the loss, manage as for other people with depression, with psychological treatments and/or antidepressants. For more information, see:
Managing a new or first presentation of depression.
Ongoing management of depression.
Table 1. Depression and grief compared.| Characteristics of grief | Characteristics of depression |
|---|---|
| Biological symptoms of loss of sleep, appetite, and concentration | Biological symptoms plus psychological symptoms of hopelessness, worthlessness, and guilt |
| Distress relates to a particular loss | Distress is usually generalized to all facets of life |
| The person retains the capacity for pleasure | The person enjoys nothing |
| Grief comes in waves | Depression is constant and unremitting |
| The person may express a passive wish for life to end | The person may express suicidal ideation |
| The person is able to look forward to the future | The person has no sense of a positive future |
| Most people cope without medical intervention | Medical or psychological intervention is usually necessary |
Basis for recommendation
Basis for recommendation
The recommendation regarding when to treat depression following bereavement is based on published expert opinion from the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders text revision (DSM-IV-TR) [American Psychiatric Association, 2000] and a narrative review of the literature [Hensley, 2006].
Scenario: Association with other psychological disorders
Scenario: Association of depression with other psychological disorders
Management
How should I manage someone with depression associated with other psychological disorders?
For people who have depression with:
Anxiety — if there is prevailing underlying depression, treat this first. Where anxiety dominates, treating the anxiety often improves depressive symptoms.
For more information, see the NICE guidelines on the management of anxiety (pdf).
Psychotic symptoms — seek expert advice. People with psychotic disorders are at risk of depression and the use of antidepressants in people with bipolar disorder can trigger hypomania/mania.
For more information, see the CKS topics on Schizophrenia and Bipolar disorder.
Dementia — treat the underlying depression.
Eating disorders — seek specialist advice. The main aim of treatment should be to treat the eating disorder.
For more information, see the CKS topic on Eating disorders.
Alcohol abuse — treat the underlying drinking problem: depressive symptoms frequently resolve following this.
For more information, see the CKS topic on Alcohol - problem drinking.
For more information on how to manage depression, see:
Managing a new or first presentation of depression.
Ongoing management of depression.
Basis for recommendation
Basis for recommendation
These recommendations are based on guidance published by the National Institute for Health and Excellence (NICE) — Depression: the treatment and management of depression in adults [National Collaborating Centre for Mental Health, 2009a; NICE, 2009a]; Dementia: supporting people with dementia and their carers in health and social care [NICE, 2006]; and Eating disorders: core interventions in the treatment and management of anorexia nervosa, bulimia nervosa and related eating disorders [NICE, 2004a]. Recommendations regarding alcohol and depression are based on guidance published by the Scottish Intercollegiate Guidelines Network (SIGN) Management of harmful drinking and alcohol dependence in primary care [SIGN, 2003].
Anxiety
NICE recommends that when depression is accompanied by symptoms of anxiety, the first priority should usually be to treat the depression [National Collaborating Centre for Mental Health, 2009a; NICE, 2009a]. This was not an evidence-based recommendation but a good practice point.
Dementia
NICE found some evidence (from four randomized controlled trials, in 137 people with dementia who also had depression) that when compared with placebo, antidepressants reduced depressive symptoms and improved general functioning [NICE, 2006].
Eating disorders
Referral for specialist advice is recommended if depression is suspected in people with an eating disorder [NICE, 2004a]. Depression is a differential diagnosis for people with an eating disorder and the person will require assessment to confirm the diagnosis. People with eating disorders and psychological complications may require admission to hospital.
Alcohol abuse
Depressive symptoms frequently resolve after alcohol detoxification [SIGN, 2003]. SIGN based this recommendation on a narrative review [Garbutt et al, 1999] and three randomized controlled trials [Kabel and Petty, 1996; Kranzler et al, 2000; Pettinati et al, 2001].
Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://medicines.org.uk/emc), or the British National Formulary (BNF) (www.bnf.org).
Contraindications
What are the contraindications of antidepressants?
All antidepressants should be avoided in people in a manic phase of bipolar disorder.
Selective serotonin reuptake inhibitors (SSRIs) — avoid in people:
Taking monoamine oxidase inhibitors (MAOIs) [ABPI Medicines Compendium, 2009a; ABPI Medicines Compendium, 2009b; Taylor et al, 2009].
Serious and sometimes fatal reactions have been reported in people receiving an SSRI in combination with an MAOI, and in people who have recently discontinued an SSRI and have been started on an MAOI.
For more information, see Switching antidepressants.
Citalopram and escitalopram [Lundbeck Ltd, 2011a; Lundbeck Ltd, 2011b; MHRA, 2011]:
Avoid:
In people with known QT interval prolongation.
In people with congenital long QT syndrome.
If the person is already taking medication know to prolong the QT interval.
Prescribe with caution in people at a higher risk than average of developing Torsade de Pointes. This includes people with:
Congestive heart failure.
Recent myocardial infarction.
Bradyarrhythmias.
Concomitant illness or medication causing a predisposition to hypokalemia or hypomagnesaemia.
Tricyclic antidepressants (TCAs) — avoid in people [BNF 58, 2009]:
Who have had a recent myocardial infarction.
Who have an arrhythmia (particularly heart block); TCAs have been associated with an increase in mortality in these people.
With severe liver disease.
Taking an MAOI.
With a history of prostatism.
With narrow angle glaucoma or other cause of increased intraocular pressure.
Mirtazapine — avoid concomitant use with MAOIs [ABPI Medicines Compendium, 2009d].
Venlafaxine — avoid in people [NICE, 2007; ABPI Medicines Compendium, 2010a]:
Taking an MAOI, or who have recently discontinued an MAOI (see Switching antidepressants for more details).
With uncontrolled hypertension.
People with pre-existing hypertension should only be prescribed venlafaxine if their blood pressure is controlled. For more information, see the CKS topic on Hypertension - not diabetic.
With a high risk of serious cardiac arrhythmias.
With a recent myocardial infarction.
Duloxetine — avoid in people [ABPI Medicines Compendium, 2009e]:
Taking an MAOI.
Taking fluvoxamine or ciprofloxacin, since the combination results in elevated plasma concentrations of duloxetine and an increased potential for adverse effects.
With liver disease resulting in hepatic impairment.
With severe renal impairment (creatinine clearance < 30 mL/min).
With uncontrolled hypertension.
Moclobemide — avoid in people [ABPI Medicines Compendium, 2009c; BNF 58, 2009]:
Who experience excitation or agitation as a predominant feature of their depression (or it should be given with a sedative such as a benzodiazepine for 2–3 weeks). Agitation and confusional states have been observed in people taking moclobemide.
Taking other antidepressants.
With phaeochromocytoma.
Advice on antidepressants
What advice should I give when starting someone on an antidepressant?
Advise the person that:
Craving and tolerance do not occur (that is the drugs are not addictive), and that taking medication should not be seen as a sign of weakness.
It can take 2–4 weeks for symptoms to improve noticeably. However, some people may experience improvement within a few days of treatment.
Treatment will need to be continued for at least 6 months after remission of symptoms (or longer, depending on the risk of relapse). The chances of staying well are greatly increased by taking antidepressants.
They need to take the medication as prescribed and must not stop the treatment suddenly — this is particularly important for drugs with a shorter half-life (for example paroxetine), in order to avoid discontinuation symptoms (for example dizziness, nausea, paraesthesiae, anxiety, diarrhoea, flu-like symptoms, and headaches).
Antidepressants can have adverse effects. If adverse effects are intolerable, the person should seek advice as it may be possible to switch to a better tolerated antidepressant.
Some antidepressants potentially have sedating effects, and may affect the person's ability to drive.
Doctors have a duty of care to advise people of the potential dangers of adverse effects of their medication.
The sedative effect of antidepressants is likely to be greatest in the first month of starting or increasing the dosage. The Driver and Vehicle Licensing Agency (DVLA) advises that people should not drive during this time if they are adversely affected.
The older tricyclic antidepressants (such as amitriptyline, clomipramine, and dosulepin) have pronounced antimuscarinic and antihistaminic effects, and therefore are likely to cause sedation. Although selective serotonin reuptake inhibitors are less likely to cause sedation, people starting on these should still be warned about this possibility.
They should be vigilant for changes in mood, increased anxiety and agitation, negativity, hopelessness, and suicidal ideas, particularly during high-risk periods (such as during initiation of and changes to medication, and at times of increased personal stress). Advise the person to seek help promptly if they are concerned.
For people taking monoamine oxidase inhibitors (MAOIs, such as moclobemide) — advise the person to check with their pharmacist before buying over-the-counter products for coughs and colds, as these often contain dextromethorphan or sympathomimetic drugs such as ephedrine, pseudoephedrine, or phenylpropanolamine.
Dextromethorphan
Dextromethorphan combined with moclobemide may cause central nervous system (CNS) excitation or depression.
Ephedrine, pseudoephedrine, and phenylpropanolamine
Combining ephedrine, pseudoephedrine, or phenylpropanolamine with moclobemide may cause elevated blood pressure. Increases in blood pressure may not be as large as those seen with non-reversible MAOIs.
Basis for recommendation
These recommendations are based on guidance issued by the National Institute for Health and Clinical Excellence (NICE) Depression; the treatment and management of depression in adults [National Collaborating Centre for Mental Health, 2009a], the Driver and Vehicle Licensing Agency (DVLA) [DVLA, 2010], the summary of product characteristics for moclobemide [ABPI Medicines Compendium, 2009c], and the Maudsley Hospital guidelines [Taylor et al, 2009].
Dose and titration
What dose should I use and how should I titrate the dose?
Prescribe the starting dose and titrate up to the recognized minimum effective dose.
Recognized starting doses and minimum effective doses are summarized in Table 1.
For selective serotonin reuptake inhibitors (SSRIs), mirtazapine, moclobemide, reboxetine, and venlafaxine, starting dosages are often effective and titration may not be necessary.
For tricyclic antidepressants (TCAs), titrate the dose to the minimum effective dose slowly (every 3–7 days), to reduce the risk of adverse effects. Consider using a lower starting dose for elderly people.
For people who show a clear clinical response to a low-dose TCA, this dose may be maintained without further dose increases, providing the person maintains the improvement.
For people not responding to the initial antidepressant, see Antidepressant choice if initial treatment fails.
Table 1. Starting doses, minimum effective doses, and maximum doses of antidepressants.| Antidepressant | Starting dose (per day) | Usual minimum effective dose (per day) | Max dose in depression (per day) |
|---|---|---|---|
| Serotonin reuptake inhibitors | |||
| Citalopram | 20 mg | 20 mg | 40 mg (20 mg in the elderly and in those with reduced hepatic function) |
| Escitalopram | 10 mg | 10 mg | 20 mg (10 mg in the elderly and in those with reduced hepatic function) |
| Fluoxetine | 20 mg | 20 mg | 60 mg |
| Paroxetine | 20 mg | 20 mg | 20 mg* |
| Sertraline | 50 mg | 50 mg | 200 mg |
| Tricyclic antidepressants | |||
| Tricyclics | 10 mg to 75 mg | At least 75 mg to 100 mg† (possibly 125 mg) | 150 mg to 200 mg |
| Lofepramine | 140 mg | 140 mg | 210 mg |
| Trazodone | 150 mg | 150 mg | 300 mg |
| Others | |||
| Duloxetine | 60 mg | 60 mg | 60 mg |
| Mirtazapine | 15 mg | 30 mg | 45 mg |
| Moclobemide | 300 mg | 300 mg | 600 mg |
| Reboxetine | 8 mg | 8 mg | 12 mg |
| Venlafaxine | 75 mg | 75 mg | 375 mg‡ |
Basis for recommendation
These recommendations are based on guidance issued by the National Institute for Health and Clinical Excellence (NICE) Depression: the treatment and management of depression in adults [NICE, 2009a], the British National Formulary [BNF 58, 2009], published expert opinion [Anderson et al, 2008], and the Maudsley hospital guideline [Taylor et al, 2009].
Doses of tricyclic antidepressants (TCAs)
NICE recommends that people who respond to a low dose of a tricyclic antidepressant (TCA) can be maintained on this dose. NICE found evidence from three randomized controlled trials (n = 222) that there is no clinically important difference between low-dose TCAs and high-dose TCAs on increasing the likelihood of achieving remission by the end of treatment (relative risk [RR] 0.99, 95% CI 0.84 to 1.16) [NICE, 2009a].
Paroxetine
The recommended target dose of paroxetine is 20 mg a day. The Committee on Safety of Medicines (CSM) advises that there is no evidence from clinical trials that increasing the dose above this level increases its efficacy in the treatment of depression [CSM, 2004a]. People who are already being successfully treated at higher doses should continue with the higher dose of paroxetine until the end of the planned course of treatment.
Suicide risk
Do antidepressants increase the risk of attempting suicide?
There is a small risk of inducing suicidal ideation in younger people (less than 30 years of age) when starting any antidepressant.
Monitor people carefully during the first few weeks of antidepressant treatment; in particular be alert for signs of suicidal ideation, akathisia, and increased anxiety and agitation. For further information, see Assessing risk of suicide.
Basis for recommendation
This recommendation is based on guidance issued by the National Institute for Health and Clinical Excellence (NICE) Depression: the treatment and management of depression in adults [NICE, 2009a], and the Medicines and Healthcare products Regulatory Agency [CSM, 2004b].
Suicide risk
Although there is evidence from a case-controlled study (n = 810) of a small but significant increase in the presence of suicidal thoughts in the early stages of antidepressant treatment [Jick et al, 2004], NICE states that this must be balanced against more recent evidence from an observational study (n = 65,103) which found that the risk of clinically important suicidal behaviour is highest in the month before starting antidepressants and decreases thereafter [Simon et al, 2006]. NICE state that it is not clear whether the increase in suicidal thoughts or behaviour is a direct result of taking an antidepressant or the timing of when the person asked for help. A possible explanation for this is that there may be a delay in noticeable improvement after starting an antidepressant, mood remains low with prominent feelings of guilt and hopelessness, but energy and motivation can increase and may be related to the increased suicidal thoughts [NICE, 2009a].
Both of the above studies found no increase in suicide, suicidal thoughts, or suicide attempts for selective serotonin reuptake inhibitors (SSRIs) compared with other antidepressants [Jick et al, 2004; Simon et al, 2006]. These results were also confirmed in two meta-analyses of randomized controlled trials [Fergusson et al, 2005; Gunnell et al, 2005] and a large nested case-controlled study [Martinez et al, 2005]. All three studies found no evidence of an increase in completed suicide with SSRIs compared with tricyclic antidepressants (TCAs). However, the two meta-analyses found that, compared with placebo, there was an increased risk of suicidal and self-harm behaviour with SSRIs.
Suicide risk in younger adults
NICE found some evidence from a large nested case-controlled study that, compared with TCAs, there is an increased risk of self-harm behaviour with SSRIs for people younger than 19 years of age [Martinez et al, 2005]. A more recent review also concluded that all antidepressants carry a small risk of inducing suicidal thoughts and suicide attempts in those younger than 25 years of age, the risk reducing at about 30–40 years of age [Möller et al, 2008]. Advice from the Medicines and Healthcare products Regulatory Agency (MHRA) suggests the cut-off should be around 30 years of age [CSM, 2004b].
A meta-analysis of observational studies found that, compared with depressed people who did not take antidepressants, adolescents receiving SSRIs had a significantly higher risk of suicide attempts and completed suicide [Barbui et al, 2009]. In contrast, adults (especially older adults) had a significantly lower risk of suicide attempts and completed suicide.
Toxicity in overdose
How toxic are antidepressants in overdose?
Selective serotonin reuptake inhibitors (SSRIs) have a better safety profile than tricyclic antidepressants (TCAs) and venlafaxine in overdose.
TCAs have potentially fatal cardiovascular effects (arrhythmia [prolongation of the QRS complex, and QT interval]) when taken in overdose. Overdose can also cause sedation, coma, hypotension, and seizures.
SSRIs have a low toxicity when taken in overdose. Overdose commonly causes vomiting, tremor, drowsiness, and tachycardia. They may also cause ST depression, seizures, and QT prolongation.
Venlafaxine commonly causes vomiting, sedation, tachycardia, and seizures when taken in overdose. Rarely, overdose may cause QT prolongation and arrhythmias. Seizures may occur after ingestion of 1 g of venlafaxine.
The safety profiles of mirtazapine, moclobemide, and reboxetine appear to be relatively good in overdose as they have not been associated with any significant cardiovascular effects.
Duloxetine — there is little information available on overdosage with this drug. Fatalities have occurred, primarily in mixed overdoses but also when duloxetine was taken alone. Vomiting, tachycardia, drowsiness, coma, convulsions, and serotonin syndrome have been reported after overdose. Prolongation of the QT and QRS duration and ventricular arrhythmias can also occur.
Basis for recommendation
This information is taken from the Maudsley hospital guidelines [Taylor et al, 2009], guidance issued by the National Institute for Health and Clinical Excellence (NICE) Depression: the treatment and management of depression in adults [NICE, 2009a], and the manufacturer's summary of product characteristics for duloxetine [ABPI Medicines Compendium, 2009e].
Fatalities associated with antidepressants
A study looking at national data for England and Wales from 1993 to 2002 found that SSRIs and TCAs were both associated with fatal poisoning, but that SSRIs were associated with lower frequencies than TCAs [Morgan et al, 2004].
TCAs were associated with 43 deaths for every 1 million prescriptions issued.
Venlafaxine was associated with 17 deaths for every 1 million prescriptions issued.
SSRIs were associated with four deaths for every 1 million prescriptions issued.
These figures should be interpreted with caution, as drugs may be used selectively in people with different severities of depression and other confounding factors are likely to be present.
Adverse effects
What adverse effects may occur with antidepressants?
There is a marked difference in tolerability of the different antidepressants from one person to another. However, selective serotonin reuptake inhibitors (SSRIs) are better tolerated than tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs), and are also better tolerated than venlafaxine and duloxetine [Taylor et al, 2009].
Adverse effects may be mild or severe, and transient or persistent [Anderson et al, 2008]:
Adverse effects that are mild and transient (for example nausea induced by SSRIs) may be managed by explanation, reassurance and, if necessary, dose reduction and re-titration.
Adverse effects that are persistent, severe, or distressing may be managed by:
Dose reduction and re-titration (if possible).
Switching antidepressants to an antidepressant less likely to cause that adverse effect.
Non-drug management (for example diet and exercise for weight gain).
Adjunctive drug treatment (for example benzodiazepines for agitation/anxiety/insomnia early in treatment, sildenafil for erectile dysfunction in men).
Hyponatraemia may occur with all antidepressants, especially in elderly people [MHRA, 1994].
Consider hyponatraemia if the person develops dizziness, drowsiness, confusion, nausea, muscle cramps, or seizures.
If hyponatraemia is suspected, stop the antidepressant and manage according to the severity and duration of symptoms, and state of hydration.
Suicidal thoughts and suicide attempts have rarely been reported for all antidepressants early in treatment or after stopping treatment. For more information, see Suicide risk.
Sexual dysfunction has been reported for all antidepressants. For more information, see Sexual dysfunction.
SSRIs
What adverse effects are associated with SSRIs?
Selective serotonin reuptake inhibitors (SSRIs) are less sedating and have fewer antimuscarinic adverse effects than tricyclic antidepressants.
The most common adverse effects associated with SSRIs are: gastrointestinal in nature and dose related (nausea, vomiting, abdominal pain, dyspepsia, constipation, and diarrhoea); central nervous system effects (dizziness, agitation, anxiety, insomnia, and tremor); headache; and sexual dysfunction [BNF 58, 2009; Taylor et al, 2009].
QT prolongation, and/or ventricular arrhythmias have been reported with citalopram or escitalopram, mainly in women, those with hypokalaemia, or those with pre-existing QT prolongation or other cardiac diseases [Lundbeck Ltd, 2011a; Lundbeck Ltd, 2011b; MHRA, 2011.]
SSRIs are also associated with an increased risk of bleeding, especially in older people or in people taking other drugs that have the potential to damage the gastrointestinal mucosa or interfere with clotting [NICE, 2009a].
Ideally, SSRIs should be avoided in people taking nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, or warfarin. For suggested alternatives to SSRIs, see Chronic physical health problems.
If no suitable alternative to an SSRI can be found, the SSRI should be prescribed with gastroprotection. For more information on which gastroprotective treatment to prescribe, see the CKS topics on NSAIDs - prescribing issues and Antiplatelet treatment.
The Medicines and Healthcare products Regulatory Agency (MHRA) has advised that epidemiological data show that SSRIs are associated with a small increased risk of fractures. However, the mechanism leading to this increased risk is unclear [MHRA, 2010].
All antidepressants are associated with discontinuation symptoms. Paroxetine is associated with a higher incidence of discontinuation symptoms than other SSRIs[NICE, 2009a].
Extrapyramidal symptoms are relatively rare and seem to be most common with paroxetine [CSM, 2000b].
TCAs
What adverse effects are associated with TCAs?
Common adverse effects of tricyclic antidepressants (TCAs) include dry mouth, blurred vision, constipation, urinary retention, sedation, and postural hypotension. Some tolerance to these adverse effects seems to develop [BNF 58, 2009].
Lofepramine has fewer antimuscarinic effects and is much less sedating.
Trazodone has no antimuscarinic effect but is very sedating.
Antimuscarinic effects can be exacerbated by other antimuscarinic drugs (for example antihistamines).
TCAs are also associated with cardiovascular effects such as electrocardiographic changes, postural hypotension, arrhythmias, heart block, tachycardia, and syncope. Arrhythmias and severe hypotension are likely to occur with high dosage or overdose [ABPI Medicines Compendium, 2008].
The Medicines and Healthcare products Regulatory Agency (MHRA) has advised that epidemiological data show that TCAs are associated with a small increased risk of fractures. However, the mechanism leading to this increased risk is unclear [MHRA, 2010].
Mirtazapine
What adverse effects are associated with mirtazapine?
Common adverse effects of mirtazapine include increased appetite, weight gain, oedema, and sedation [BNF 58, 2009].
Drowsiness often occurs during the first few weeks of treatment. This effect is not dose-related and should not prompt a reduction in dose (as this will lead to reduced efficacy). In most people this drowsiness is transient, but people taking mirtazapine should be advised not to drive or operate machinery if they experience it [Organon Labs Ltd., 2004].
Increased appetite and weight gain commonly occur in people taking mirtazapine [ABPI Medicines Compendium, 2009d]. This should be taken into account before prescribing mirtazapine for people who are overweight or obese, or who have an eating disorder.
Reversible blood dyscrasias, including agranulocytosis, have been reported infrequently in people taking mirtazapine. This usually occurs after 4–6 weeks of treatment and is reversible after stopping treatment [ABPI Medicines Compendium, 2009d].
Advise people to report symptoms such as fever, sore throat, stomatitis, or other signs of infection.
If blood dyscrasia is suspected, stop treatment and check full blood count.
Reboxetine
What adverse effects are associated with reboxetine?
Common adverse effects include insomnia, sweating, dizziness, dry mouth, constipation, nausea, tachycardia, urinary hesitancy, and headache [ABPI Medicines Compendium, 2009f; Taylor et al, 2009].
Moclobemide
What adverse effects are associated with moclobemide?
Common adverse effects include, sleep disturbance, nausea, agitation, and confusion [Taylor et al, 2009].
Agitation and confusional states have been seen in people taking moclobemide. It should be avoided in people who experience excitation or agitation as a predominant feature of their depression (or it should be given with a sedative such as benzodiazepine for 2–3 weeks) [ABPI Medicines Compendium, 2009c; BNF 58, 2009].
Venlafaxine
What adverse effects are associated with venlafaxine?
The most common adverse effects are nausea, insomnia, dry mouth, somnolence, dizziness, constipation, sweating, nervousness, and asthenia. They are thought to be dose-related and transient.
Cardiac adverse effects include hypertension, palpitations, and vasodilatation. Less commonly, venlafaxine may cause hypotension/postural hypotension, syncope, arrhythmias (including tachycardia), Torsade de Pointes, QT prolongation, ventricular tachycardia, and ventricular fibrillation.
Hypertension may occur in people taking venlafaxine, especially those taking high doses [NICE, 2007]. People taking venlafaxine (including people with pre-existing hypertension) require monitoring for the signs and symptoms of cardiac dysfunction and any increase in blood pressure.
Increased risk of bleeding — venlafaxine is associated with an increased risk of bleeding, especially in older people or in people taking other drugs that have the potential to damage the gastrointestinal mucosa or interfere with clotting[National Collaborating Centre for Mental Health, 2009b; ABPI Medicines Compendium, 2010a].
Ideally, venlafaxine should be avoided in people taking nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, or warfarin. For suggested alternatives to SSRIs, see Chronic physical health problems.
If no suitable alternative to venlafaxine can be found, venlafaxine should be prescribed with gastroprotection. For more information on which gastroprotective treatment to prescribe, see the CKS topics on NSAIDs - prescribing issues and Antiplatelet treatment.
Glycaemic control — monitor diabetic control in people taking venlafaxine who have diabetes mellitus because venlafaxine may alter glycaemic control. The doses of insulin and oral anti-diabetic drugs may need to be altered [ABPI Medicines Compendium, 2011b].
Duloxetine
What adverse effects are associated with duloxetine?
The main adverse effects of duloxetine include nausea, insomnia, dizziness, dry mouth, somnolence, constipation, and anorexia [Taylor et al, 2009].
Duloxetine is associated with small increases in blood pressure.
Monitor blood pressure in people with known hypertension or other cardiac disease and those whose conditions could be affected by an increase in blood pressure.
Consider reducing the dose or gradual discontinuation in people who experience a sustained increase in blood pressure while taking duloxetine.
Increased risk of bleeding — duloxetine may be associated with an increased risk of bleeding, especially in older people or in people taking other drugs that have the potential to damage the gastrointestinal mucosa or interfere with clotting[ABPI Medicines Compendium, 2009e; National Collaborating Centre for Mental Health, 2009b].
Ideally, duloxetine should be avoided in people taking nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, or warfarin. For suggested alternatives to SSRIs, see Chronic physical health problems.
If no suitable alternative to duloxetine can be found, duloxetine should be prescribed with gastroprotection. For more information on which gastroprotective treatment to prescribe, see the CKS topics on NSAIDs - prescribing issues and Antiplatelet treatment.
Treatment with duloxetine has been associated with an increase in fasting plasma glucose.
The clinical significance of this is not clear, but it may be prudent to monitor blood glucose in people who are taking duloxetine.
Sexual dysfunction
What sexual adverse affects are associated with antidepressants and how do I manage them?
Sexual dysfunction is a common symptom of depression. However, in addition to this, all antidepressants can cause sexual dysfunction to varying degrees (most commonly serotonin reuptake inhibitors). See Table 1 for more information.
If the person experiences sexual dysfunction caused by an antidepressant, the treatment options include:
A period of watchful waiting (spontaneous remission occurs in 10% of people).
Reducing the dose of the antidepressant (the impact of antidepressants on sexual function is thought to be dose dependent).
Switching antidepressants to an antidepressant which is less likely to cause the specific problem.
Adjunctive treatment with a phosphodiesterase inhibitor (such as sildenafil) for erectile dysfunction. For more information, see the CKS topic on Erectile dysfunction.
Table 1. Sexual adverse effects of antidepressants.| Drug | Prevalence | Type of problem experienced |
|---|---|---|
| Selective serotoinin inhibitors (SSRIs) | 60–70% | All phases of the sexual response. Paroxetine is associated with more erectile dysfunction and vaginal dryness than other SSRIs. |
| Tricyclic antidepressants (TCAs) | 30% | Decreased libido, erectile dysfunction, delayed orgasm, and impaired ejaculation. |
| Venlafaxine | 70% | Decreased libido, delayed orgasm, and erectile dysfunction. |
| Mirtazapine | 25% | Decreased libido, delayed orgasm, erectile dysfunction, absence of orgasm. |
| Reboxetine | 5–10% | Orgasm abnormalities. |
| Duloxetine | 46% | All phases of the sexual response. |
| Irreversible monoamine oxidase inhibitors (MAOIs) | 40% | Decreased libido, erectile dysfunction, delayed orgasm, and impaired ejaculation.Moclobemide is less likely to cause sexual dysfunction compared with older MAOIs (4% versus 40%). |
Basis for recommendation
These recommendations are based on information in the Maudsley hospital guidelines [Taylor et al, 2009] and published expert opinion [Kennedy and Rizvi, 2009].
Drug interactions
Drug interactions
SSRIs
What key drug interactions with SSRIs should I be aware of?
Fluoxetine, fluvoxamine, and paroxetine are associated with a higher propensity for drug interactions than other selective serotonin reuptake inhibitors (SSRIs) [NICE, 2009a].
Citalopram and escitalopram are contraindicated if the person is already taking a medication known to prolong the QT interval [Lundbeck Ltd, 2011a; Lundbeck Ltd, 2011b; MHRA, 2011]. These drugs include [MHRA, 2011]:
Antiarrhythmics such as amiodarone, dronedarone, quinidine.
Antipsychotics such as phenothiazine (fentiazine) derivatives, pimozide, haloperidol.
Tricyclic antidepressants.
Some antimicrobials such as sparfloxacin, moxifloxacin, intravenous erythromycin.
Some antimalarials such as halofantrine.
Some antihistamines such as astemizole and mizolastine.
Some antiretrovirals such as ritonavir, saquinavir, lopinavir.
Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) — SSRIs inhibit platelet aggregation and increase the risk of bleeding, especially in older people or in people taking aspirin or an NSAID [NICE, 2009a].
Consider prescribing a gastroprotective drug in older people who are taking NSAIDs or aspirin.
For more information on which gastroprotective treatment to prescribe, see the CKS topics on NSAIDs - prescribing issues and Antiplatelet treatment.
Warfarin — SSRIs may enhance the anticoagulant effect of warfarin.
Serotonergic drugs (such as tramadol, triptans) or dopaminergic drugs (such as selegiline) — concomitant treatment may increase the risk of serotonin syndrome and close monitoring is advised [BNF 58, 2009].
Serotonin syndrome is characterized by altered mental status, neuromuscular hyperactivity, and autonomic instability [NPIS, 2009]. The person may suffer from agitation, confusion, delirium, and hallucinations.
Neuromuscular features occur in around 50% of people and include profound shivering, tremor, teeth grinding, myoclonus, and hyperreflexia.
Autonomic instability occurs in around 50% of people. Features include tachycardia, fever, and hypertension or hypotension. Flushing, diarrhoea, and vomiting are also common.
In severe cases, drowsiness, coma, seizure, hyperthermia, rhabdomyolysis, renal failure, and coagulopathies may develop.
St John's wort — co-administration with an SSRI causes an increased risk of serotonergic effects and an increased incidence of adverse effects [CSM, 2000a]. Advise people that they should not take St John's wort while they are taking an SSRI [BNF 58, 2009].
Antiepileptics — SSRIs antagonize the anti-convulsive effect of antiepileptics, but they are thought to have a low proconvulsant effect, the seizure risk being dose-related, and are a good choice of antidepressant for people with epilepsy [BNF 58, 2009; Taylor et al, 2009].
Moclobemide — do not give moclobemide with other SSRIs, and ensure that there is an adequate washout period when switching from another antidepressant to moclobemide (or vice versa) [Baxter, 2008]. There are reports of serotonin syndrome.
Tamoxifen — avoid concurrent use with fluoxetine or paroxetine. Fluoxetine and paroxetine are potent inhibitors of the liver enzyme CYP2D6 and may reduce the plasma concentration of tamoxifen, leading to reduced efficacy [ABPI Medicines Compendium, 2010b; ABPI Medicines Compendium, 2011a].
TCAs
What key drug interactions with TCAs should I be aware of?
Sedative drugs or alcohol — tricyclic antidepressants (TCAs) are sedating and co-administration with other sedating drugs or alcohol may have a synergistic effect.
Antihistamines and antipsychotics — TCAs have antimuscarinic effects (dry mouth, blurred vision, constipation), which can be exacerbated by other drugs which cause antimuscarinic effects (such as antihistamines and antipsychotics).
Antiarrhythmics — there is an increased risk of ventricular arrhythmias when TCAs are given with antiarrhythmics.
Serotonergic drugs (such as tramadol, triptans) or dopaminergic drugs (such as selegiline) — concomitant treatment may increase the risk of serotonin syndrome. Close monitoring is advised.
Moclobemide — do not give moclobemide with other TCAs, and ensure that there is an adequate washout period when switching from another antidepressant to moclobemide (or vice versa) [Baxter, 2008]. There are reports of serotonin syndrome.
Warfarin — people taking warfarin should receive careful coagulation monitoring when treatment with a TCA is initiated or stopped; TCAs may enhance or reduce the anticoagulant effect of warfarin.
Mirtazapine
What key drug interactions with mirtazapine should I be aware of?
Alcohol — mirtazapine has a sedative effect and co-administration with other sedating drugs or alcohol may have a synergistic effect.
Moclobemide — do not give moclobemide with mirtazapine, and ensure that there is an adequate washout period when switching from mirtazapine to moclobemide (or vice versa) [Baxter, 2008]. There are reports of serotonin syndrome.
Warfarin — there is limited evidence that mirtazapine may enhance the anticoagulant effect of warfarin [Baxter, 2008; BNF 58, 2009].
Reboxetine
What key drug interactions with reboxetine should I be aware of?
Macrolide antibiotics (for example erythromycin or clarithromycin), imidazole antifungals (for example ketoconazole, fluconazole) and fluvoxamine — can reduce the metabolism of reboxetine, increasing the risk of adverse effects [ABPI Medicines Compendium, 2009f].
Moclobemide — do not give moclobemide with reboxetine, and ensure that there is an adequate washout period when switching from reboxetine to moclobemide (or vice versa) [Baxter, 2008]. There are reports of serotonin syndrome.
Moclobemide
What key drug interactions with moclobemide should I be aware of?
Food — the manufacturers of moclobemide advise people to avoid taking large quantities of tyramine-rich foods (such as mature cheese, yeast extracts, and fermented soya bean products). Tyramine (150 mg) increases systolic blood pressure by 30 mmHg when given with moclobemide. This amount of tyramine is found in 200 g of stilton cheese and 300 g of gorgonzola cheese. These are excessive amounts of cheese to eat in a few minutes and most people do not need to follow the special dietary restrictions [Baxter, 2008]. Moclobemide causes less potentiation of tyramine than that caused by irreversible monoamine oxidase inhibitors (MAOIs) such as phenelzine [BNF 58, 2009].
Dopaminergic drugs (for example levodopa or selegiline) — there is an increased risk of adverse effects when moclobemide is given with dopaminergic agents [BNF 58, 2009].
Other antidepressants — do not give moclobemide with other antidepressants, and ensure that there is an adequate washout period when switching from another antidepressant to moclobemide (or vice versa) [Baxter, 2008]. There are reports of serotonin syndrome.
Over-the-counter products for coughs and colds; containing dextromethorphan, ephedrine, and pseudoephedrine
Dextromethorphan
Dextromethorphan combined with moclobemide may cause central nervous system (CNS) excitation or depression [ABPI Medicines Compendium, 2009c].
Ephedrine, pseudoephedrine, and phenylpropanolamine
Combining ephedrine, pseudoephedrine, or phenylpropanolamine with moclobemide may cause elevated blood pressure. Increases in blood pressure may not be as large as those seen with irreversible MAOIs.
Advise people to check with their pharmacist before buying over-the-counter products for coughs and colds, as these often contain dextromethorphan or sympathomimetic drugs (such as ephedrine, pseudoephedrine, or phenylpropanolamine).
Venlafaxine
What key drug interactions with venlafaxine should I be aware of?
Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) — selective serotonin reuptake inhibitors (SSRIs) inhibit platelet aggregation and increase the risk of bleeding, especially in older people or those taking aspirin or an NSAID [NICE, 2009a]. Venlafaxine is a serotonin noradrenaline reuptake inhibitor (SNRI) and is thought to have the same profile as SSRIs.
Consider prescribing a gastroprotective drug in older people who are taking NSAIDs or aspirin.
For more information on which gastroprotective treatment to prescribe, see the CKS topics on NSAIDs - prescribing issues and Antiplatelet treatment.
Warfarin — venlafaxine may enhance the anticoagulant effect of warfarin [ABPI Medicines Compendium, 2010a].
Moclobemide — do not give moclobemide with venlafaxine, and ensure that there is an adequate washout period when switching from venlafaxine to moclobemide (or vice versa) [Baxter, 2008]. There are reports of serotonin syndrome.
Duloxetine
What key drug interactions with duloxetine should I be aware of?
Tramadol or other antidepressants (including St John's wort) — avoid concomitant use because this may lead to serotonin syndrome [Baxter, 2008].
Ciprofloxacin — avoid concomitant use because the metabolism of duloxetine is inhibited by ciprofloxacin.
Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) — selective serotonin reuptake inhibitors (SSRIs) inhibit platelet aggregation and increase the risk of bleeding, especially in older people or those taking aspirin or an NSAID [NICE, 2009a]. Duloxetine is a serotonin noradrenaline reuptake inhibitor (SNRI) and is thought to have the same profile as SSRIs.
Consider prescribing a gastroprotective drug in older people who are taking NSAIDs or aspirin.
For more information on which gastroprotective treatment to prescribe, see the CKS topics on NSAIDs - prescribing issues and Antiplatelet treatment.
Warfarin — duloxetine may enhance the anticoagulant effect of warfarin [ABPI Medicines Compendium, 2009e].
Monitoring antidepressants
How should I monitor someone taking antidepressants?
Monitor the person closely in the early stages of treatment, irrespective of which antidepressant is prescribed, to assess response, adverse effects, compliance, and suicide risk. People considered at increased risk of suicide should be seen at least once a week [NICE, 2009a]. For more information, see Assessing risk of suicide.
Hyponatraemia has been associated with all types of antidepressants [CSM, 2000b; Taylor et al, 2009].
Monitor for signs and symptoms of hyponatraemia (dizziness, lethargy, nausea, confusion, cramps, seizures).
If hyponatraemia is suspected, stop the antidepressant and manage according to the severity and duration of symptoms, and state of hydration.
Risk factors for developing hyponatraemia include a history of hyponatraemia, extreme old age (greater than 80 years of age), female sex, low body weight, diuretics, diabetes mellitus, hypertension, reduced renal function, and chronic obstructive pulmonary disease.
Hypertension — venlafaxine and duloxetine have both been associated with increases in blood pressure [ABPI Medicines Compendium, 2009e; ABPI Medicines Compendium, 2010a].
Venlafaxine
Monitor the person (including those with pre-existing hypertension) for signs and symptoms of cardiac dysfunction and any increase in blood pressure [NICE, 2007].
Monitor blood pressure on initiation and regularly during treatment (especially during dose titration). If there is a sustained increase in blood pressure there are two options; reduce the dose or discontinue treatment.
Duloxetine
Monitor blood pressure in people with known hypertension or other cardiac disease and those whose condition could be affected by an increase in blood pressure [ABPI Medicines Compendium, 2009e].
Consider reducing the dose or gradual discontinuation in people who experience a sustained increase in blood pressure while taking duloxetine.
QT prolongation, and/or ventricular arrhythmias including Torsade de Pointes have been reported in people taking citalopram or escitalopram [Lundbeck Ltd, 2011a; Lundbeck Ltd, 2011b; MHRA, 2011].
Before starting treatment with citalopram or escitalopram:
Consider an ECG and measurement of the QT interval in people with cardiac disease.
Correct electrolyte imbalances such as hypokalaemia and hypomagnesaemia.
Monitor serum magnesium in elderly people taking diuretics or proton pump inhibitors.
If cardiac symptoms such as palpitations, vertigo, syncope, or seizures develop during treatment, arrange for the person to have an ECG:
If the QTc interval (QT interval corrected for heart rate) is greater than 500 milliseconds, withdraw treatment gradually.
If the QTc interval is between 480 and 500 milliseconds, the risks and benefits of continuing treatment should be carefully considered, alongside options for dose reduction or gradual withdrawal.
Stopping antidepressants
How should antidepressants be stopped?
In general, reduce the dose or frequency of the antidepressant gradually over a 4-week period to minimize discontinuation symptoms.
Discontinuation symptoms include dizziness, nausea, paraesthesiae, anxiety, diarrhoea, flu-like symptoms, and headache. They may occur when stopping or reducing the dose of any antidepressant.
Onset is usually within 5 days of stopping treatment. Occasionally, symptoms occur during tapering or after missed doses.
These symptoms are usually mild and self-limiting, rarely lasting for more than 1–2 weeks. However, occasionally they can be severe, particularly if the drug is stopped abruptly.
Discontinuation symptoms are more common with longer treatment courses, and rarely occur with treatments lasting less than 8 weeks.
Discontinuation symptoms are more likely with antidepressants with a short half-life (such as paroxetine), in people who developed anxiety symptoms at the start of treatment, and in people taking other centrally-acting drugs.
A shorter or longer tapering period may be required in the following circumstances:
For people with severe adverse reactions to treatment (for example cardiac arrhythmia with a tricyclic antidepressant) — a more rapid (abrupt) discontinuation may be necessary.
For people who have been receiving longer-term maintenance treatment — taper the dose over 6 months.
For people taking fluoxetine — treatment can be stopped abruptly because fluoxetine has a long half-life and active metabolites. However, people taking higher doses (40 mg to 60 mg daily) may require gradual withdrawal.
Advise the person to seek advice if they experience significant discontinuation symptoms.
If discontinuation symptoms are mild, reassure the person that they will pass in a few days — this is often all that is required.
If discontinuation symptoms are severe, consider reintroducing the original antidepressant at a dose not associated with discontinuation symptoms (or another antidepressant with a longer half-life from the same class) and then taper more slowly while monitoring symptoms.
Switching antidepressants
How should I switch from one antidepressant to another?
When switching from one antidepressant to another, be aware of the need for gradual and modest incremental increases of dose, of interactions between antidepressants, and of the risk of serotonin syndrome when combinations of serotonergic antidepressants are prescribed. Features of serotonin syndrome include confusion, delirium, shivering, sweating, changes in blood pressure, and myoclonus.
Abrupt withdrawal should generally be avoided when switching from one antidepressant to another.
Cross tapering is usually preferred (an example of a cross-tapering regimen is shown in Table 1). However in some instances it may be possible to withdraw the current antidepressant and start the new antidepressant the next day. For example when switching from one serotonin reuptake inhibitor (SSRI) to another SSRI or a serotonin norepinephrine reuptake inhibitor (SNRI); the exception to this is fluoxetine.
When switching from any antidepressant to moclobemide (a reversible inhibitor of monoamine oxidase), great care should be taken.
If switching from an SSRI to moclobemide, withdraw the SSRI and wait for at least 2 weeks (at least 5 weeks if the SSRI was fluoxetine) before starting moclobemide.
When switching from a tricyclic antidepressant (TCA) to moclobemide, withdraw the TCA and wait at least 1 week before starting moclobemide.
When switching from moclobemide to an SSRI, TCA, trazodone, mirtazapine, or reboxetine, withdraw moclobemide and wait at least 24 hours before starting another antidepressant.
Table 1. An example of a cross-tapering regimen — switching from a selective serotonin reuptake inhibitor to a tricyclic antidepressant, or vice versa.| Pre-switch dosage | Week 1 | Week 2 | Week 3 | Week 4 | |
|---|---|---|---|---|---|
| Withdrawing citalopram | 20 mg daily | 20 mg daily | 10 mg daily | 10 mg daily | nil |
| Introducing amitriptyline | Nil | 25 mg daily | 50 mg daily | 100 mg daily | 150 mg daily |
Basis for recommendation
The suggested cross-tapering regimen is that proposed by the Maudsley hospital guideline [Taylor et al, 2009]. Local practice may vary.
From a TCA
Switching from a TCA to different TCA or to another type of antidepressant
When switching from a tricyclic antidepressant (TCA) to:
Another TCA — cross-taper cautiously.
Trazodone — halve dosage and add trazodone, then slow withdrawal.
Citalopram, escitalopram, sertraline, paroxetine — halve dosage and add citalopram, escitalopram, sertraline, or paroxetine, then slow withdrawal.
Fluoxetine — halve dosage and add fluoxetine, then slow withdrawal.
Duloxetine — cross-taper cautiously; start at 60 mg every other day, increase slowly.
Mirtazapine — cross-taper cautiously.
Reboxetine — cross-taper cautiously.
Moclobemide — withdraw (gradually reduce the dose then stop) and then wait at least 1 week before starting moclobemide.
Venlafaxine — cross-taper cautiously, starting with venlafaxine 37.5 mg daily.
Basis for recommendation
The suggested switching regimens recommended by CKS are those proposed by the Maudsley hospital guideline [Taylor et al, 2009]. Local practice may vary.
From trazodone
Switching from trazodone to another antidepressant
When switching from trazodone to:
A tricyclic antidepressant (TCA) — cross-taper cautiously with very low dosage of TCA.
Citalopram, escitalopram, sertraline, paroxetine — withdraw (gradually reduce dose then stop), then start citalopram, escitalopram, sertraline, or paroxetine.
Duloxetine — withdraw (gradually reduce the dose then stop), and then start at 60 mg every other day and increase slowly.
Fluoxetine — withdraw (gradually reduce the dose then stop) and then start fluoxetine.
Mirtazapine — cross-taper cautiously.
Reboxetine — withdraw (gradually reduce the dose then stop), and then start reboxetine 2 mg twice a day and increase cautiously.
Moclobemide — withdraw (gradually reduce the dose then stop) and then wait at least 1 week before starting moclobemide.
Venlafaxine — cross-taper cautiously. Start venlafaxine at 37.5 mg each day.
Basis for recommendation
The suggested switching regimens recommended by CKS are those proposed by the Maudsley hospital guideline [Taylor et al, 2009]. Local practice may vary.
From citalopram, escitalopram, sertraline, or paroxetine
Switching from citalopram, escitalopram, sertraline, or paroxetine to another antidepressant
When switching from citalopram, escitalopram, sertraline, or paroxetine to:
A tricyclic antidepressant — cross-taper cautiously.
Trazodone — withdraw (gradually reduce the dose then stop), and then start trazodone.
Fluoxetine — withdraw (gradually reduce the dose then stop), and then start fluoxetine 10 mg each day.
Duloxetine — abrupt switch possible. Start at 60 mg each day.
Mirtazapine — cross-taper cautiously.
Reboxetine — cross-taper cautiously.
Moclobemide — withdraw (gradually reduce the dose then stop) and then wait at least 1 week before starting moclobemide.
Venlafaxine — cross-taper cautiously. Start venlafaxine 37.5 mg daily and increase very slowly.
Basis for recommendation
The suggested switching regimens recommended by CKS are those proposed by the Maudsley hospital guideline [Taylor et al, 2009]. Local practice may vary.
From fluoxetine
Switching from fluoxetine to another antidepressant
When switching from fluoxetine to:
A tricyclic antidepressant (TCA) — stop fluoxetine. Wait 4–7 days. Start TCA at a very low dose and increase very slowly.
Trazodone — stop fluoxetine. Wait 4–7 days. Start low-dose trazodone.
Citalopram, escitalopram, sertraline, paroxetine — stop fluoxetine. Wait 4–7 days, then start citalopram (10 mg each day), escitalopram (10 mg each day), sertraline (25 mg each day), or paroxetine (10 mg each day); and increase slowly.
Duloxetine — abrupt switch possible. Start at 60 mg each day.
Mirtazapine — withdraw (gradually reduce the dose then stop), and then wait 4–7 days before starting mirtazapine cautiously.
Reboxetine — withdraw (gradually reduce the dose then stop). Start reboxetine at 2 mg twice a day and increase cautiously.
Moclobemide — withdraw (gradually reduce the dose then stop) and then wait at least 5 weeks before starting moclobemide.
Venlafaxine — withdraw (gradually reduce the dose then stop) and then start venlafaxine at 37.5 mg each day. Increase very slowly.
Basis for recommendation
The suggested switching regimens recommended by CKS are those proposed by the Maudsley hospital guideline [Taylor et al, 2009]. Local practice may vary.
From mirtazapine
Switching from mirtazapine to another antidepressant
When switching from mirtazapine to:
A tricyclic antidepressant (TCA) — withdraw (gradually reduce the dose then stop) and then start TCA.
Trazodone — withdraw (gradually reduce the dose then stop) and then start trazodone.
Citalopram, escitalopram, sertraline, or paroxetine — withdraw (gradually reduce the dose then stop) and then start citalopram, escitalopram, sertraline, or paroxetine.
Duloxetine — withdraw (gradually reduce the dose then stop) and then start duloxetine at 60 mg every other day. Increase slowly.
Reboxetine — withdraw (gradually reduce the dose then stop) and then start reboxetine.
Moclobemide — withdraw (gradually reduce the dose then stop) and then wait 1 week before starting moclobemide.
Venlafaxine — cross-taper cautiously.
Basis for recommendation
The suggested switching regimens recommended by CKS are those proposed by the Maudsley hospital guideline [Taylor et al, 2009]. Local practice may vary.
From reboxetine
Switching from reboxetine to another antidepressant
When switching from reboxetine to:
A tricyclic antidepressant (TCA) — cross-taper cautiously.
Trazodone — cross-taper cautiously.
Citalopram, escitalopram, sertraline, or paroxetine — cross taper cautiously.
Duloxetine — cross-taper cautiously.
Mirtazapine — cross-taper cautiously.
Moclobemide — withdraw (gradually reduce the dose then stop) and then wait at least 1 week before starting moclobemide.
Venlafaxine — cross-taper cautiously.
Basis for recommendation
The suggested switching regimens recommended by CKS are those proposed by the Maudsley hospital guideline [Taylor et al, 2009]. Local practice may vary.
From moclobemide
Switching from moclobemide to another antidepressant
When switching from moclobemide to:
A tricyclic antidepressant (TCA) — withdraw (gradually reduce the dose then stop) and then wait 24 hours.
Trazodone — withdraw (gradually reduce the dose then stop) and then wait 24 hours.
Citalopram, escitalopram, sertraline, or paroxetine — withdraw (gradually reduce the dose then stop) and then wait 24 hours.
Fluoxetine — withdraw (gradually reduce the dose then stop) and then wait 24 hours.
Duloxetine — withdraw (gradually reduce the dose then stop) and then wait 24 hours.
Mirtazapine — withdraw (gradually reduce the dose then stop) and then wait 24 hours.
Reboxetine — withdraw (gradually reduce the dose then stop) and then wait 24 hours.
Venlafaxine — withdraw (gradually reduce the dose then stop) and then wait 24 hours.
Basis for recommendation
The suggested switching regimens recommended by CKS are those proposed by the Maudsley hospital guideline [Taylor et al, 2009]. Local practice may vary.
From duloxetine
Switching from duloxetine to another antidepressant
When switching from duloxetine to:
A tricyclic antidepressant (TCA) — cross-taper cautiously with a very low dose of antidepressant.
Trazodone — withdraw (gradually reduce the dose then stop), and then start trazodone.
Citalopram, escitalopram, sertraline, or paroxetine — withdraw then start citalopram, escitalopram, sertraline, or paroxetine.
Fluoxetine — withdraw (gradually reduce the dose then stop) and then start fluoxetine.
Moclobemide — withdraw (gradually reduce the dose then stop) and then wait 1 week before starting moclobemide.
Mirtazapine — withdraw (gradually reduce the dose then stop) and then start mirtazapine.
Reboxetine — cross-taper cautiously.
Venlafaxine — withdraw (gradually reduce the dose then stop) and then start venlafaxine.
Basis for recommendation
The suggested switching regimens recommended by CKS are those proposed by the Maudsley hospital guideline [Taylor et al, 2009]. Local practice may vary.
From venlafaxine
Switching from venlafaxine to another antidepressant
When switching from venlafaxine to:
A tricyclic antidepressant (TCA) — cross-taper cautiously with a very low dose of antidepressant.
Trazodone — cross-taper cautiously.
Citalopram, escitalopram, sertraline, or paroxetine — cross-taper cautiously.
Fluoxetine — cross-taper cautiously. Start with 20 mg every other day.
Moclobemide — withdraw (gradually reduce the dose then stop) and then wait 1 week before starting moclobemide.
Mirtazapine — cross-taper cautiously.
Reboxetine — cross-taper cautiously.
Duloxetine — withdraw. Start at 60 mg every other day. Increase slowly.
Basis for recommendation
The suggested switching regimens recommended by CKS are those proposed by the Maudsley hospital guideline [Taylor et al, 2009]. Local practice may vary.
St John's wort
What interactions may occur with St John's wort?
St John's wort is an extract of the plant Hypericum perforatum, which has been used historically to treat depression. It contains at least 10 constituents, including naphthodianthrons, flavonoids, xanthons, and biflavonoids. It is not a licensed medicine, but is available over the counter in pharmacies and health food stores.
There are a number of different St John's wort preparations available, many of which are not standardized. Some preparations have been granted a traditional herbal registration certificate (based on traditional use, rather than evidence of efficacy).
Although the mode of action of St John's wort is unclear, it is thought that it may inhibit the reuptake of serotonin and noradrenaline, inhibit monoamine oxidase, up-regulate serotonin receptors, and/or decrease serotonin receptor expression.
St John's wort is known to interact with other drugs (including oral contraceptives, anticoagulants, and anticonvulsants) [CSM, 2000a] and have adverse effects (for example photosensitivity).
The National Institute for Health and Clinical Excellence states that St John's wort should not be advised for people with depression because of uncertainty about appropriate doses, persistence of effect, variation in the nature of preparations, and potential serious interactions with other drugs.
[National Collaborating Centre for Mental Health, 2009a; Taylor et al, 2009]
Chronic physical health problems
Which antidepressants are recommended for people with chronic physical health problems?
In general, if the person has depression and a chronic health problem, consider prescribing a generic selective serotonin reuptake inhibitor (SSRI), such as sertraline, unless these are contraindicated or there is a significant drug interaction [NICE, 2009b]. Do not use citalopram or escitalopram in people who are taking medication that could prolong the QT interval [Lundbeck Ltd, 2011a; Lundbeck Ltd, 2011b; MHRA, 2011]. For more information on interactions specific for citalopram and escitalopram see the section on prescribing information.
For a brief summary on which antidepressants may be prescribed for people with chronic physical health problems, see Table 1. For more detailed information see appendix 16 of the full NICE guideline (pdf).
Table 1. Antidepressants recommended for people with a chronic physical health problem.| Medication being taken for a chronic physical health problem | Recommended antidepressant(s) |
|---|---|
| Nonsteroidal anti-inflammatory drugs (NSAIDs) | Do not normally offer an SSRI or an SNRI — but if no suitable alternative can be found, offer gastroprotection in addition to an SSRI or SNRI.Consider any alternative (for example mirtazapine, moclobemide, reboxetine, or trazodone). |
| Warfarin | Do not normally offer mirtazapine*, TCAs, SSRIs, or SNRIs.Consider reboxetine, trazodone, or mianserin. |
| Heparin | Do not normally offer an SSRI or an SNRI.Consider any alternative (for example mirtazapine, trazodone, reboxetine, or a TCA). |
| Aspirin | Use SSRIs and SNRIs with caution — if no suitable alternative can be found, offer gastroprotection in addition to an SSRI.When aspirin is used alone, consider trazadone or reboxetine.Consider mirtazapine. |
| Anti-epileptic drugs † | Complex interactions — seek specialist advice.Consider whether depression may be worsened by the anti-epileptic drug.All antidepressants lower the seizure threshold.SSRIs may be used first line with caution.Consider moclobemide second line. |
| Triptan drugs for migraine | Do not offer SSRIs.Offer mirtazapine, trazadone, mianserin, or reboxetine. |
| MAO-B inhibitors (such as selegiline and rasagiline) | Do not normally offer SSRIs.Offer mirtazapine, trazadone, mianserin, or reboxetine. |
| Clozapine, methadone, tizanidine | Do not normally offer fluvoxamine.Do not offer citalopram or escitalopramOffer sertraline. |
| Theophylline | Do not normally offer fluvoxamine.Offer sertraline or citalopram |
| Flecainide or propafenone | Do not offer citalopram or escitalopram.Offer sertraline as the preferred antidepressant.Mirtazapine and moclobemide may also be used. |
| Atomoxetine | Do not offer fluoxetine, paroxetine, citalopram, or escitalopram.Offer a different SSRI. |
Pregnancy and breastfeeding
What are the issues related to antidepressants in pregnancy and breastfeeding?
For information on the management of women with depression who are pregnant or breastfeeding, see the CKS topic on Depression - antenatal and postnatal.
Evidence
Evidence
Supporting evidence
A brief summary of the evidence is given in the Basis for recommendation sections of the individual recommendations within this CKS topic. For a more detailed discussion of the evidence, see the NICE guideline (pdf) Depression: the treatment and management of depression in adults [NICE, 2009a].
Search strategy
Scope of search
A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on the primary care management of Depression in adults (> 18 years), with additional searches in the following areas:
Seasonal affective disorder
Depression associated with bereavement
Risk of suicide
Adverse bleeding during venlaxafine therapy
The search excluded depression in pregnant women and women with postnatal depression, children and adolescents.
Search dates
Medline and Embase; January 2005 – October 2009
Key search terms
Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline and these were adapted for other databases. Further details are available on request.
exp Depression/, exp Depressive Disorder/, exp Dysthymic Disorder/, exp Seasonal Affective Disorder/, (depression or depressive disorder or dysthymic disorder or seasonal affective disorder).mp. or depression, reactive.sh
exp Serotonin Uptake Inhibitors/, exp Paroxetine/, exp Citalopram/, exp Fluoxetine/, venlaxafine.tw
exp Antidepressive Agents, Tricyclic/, exp Antidepressive Agents/, exp Monoamine Oxidase Inhibitors/
exp Cognitive Therapy/, exp Psychotherapy/
exp Hypericum/, st johns wort.tw
exp Bereavement/
exp Gastrointestinal Hemorrhage/
Table 1. Key to search terms.| Search commands | Explanation |
|---|---|
| / | indicates a MeSh subject heading with all subheadings selected |
| .tw | indicates a search for a term in the title or abstract |
| exp | indicates that the MeSH subject heading was exploded to include the narrower, more specific terms beneath it in the MeSH tree |
| $ | indicates that the search term was truncated (e.g. wart$ searches for wart and warts) |
Sources of guidelines
National Institute for Health and Clinical Excellence (NICE)
Scottish Intercollegiate Guidelines Network (SIGN)
National Guidelines Clearinghouse
British Columbia Medical Association
Institute for Clinical Systems Improvement
Guidelines International Network
National Library of Guidelines
National Health and Medical Research Council (Australia)
University of Michigan Medical School
Michigan Quality Improvement Consortium
National Resource for Infection Control
NHS Scotland National Patient Pathways
Agency for Healthcare Research and Quality
UK Ambulance Service Clinical Practice Guidelines
RefHELP NHS Lothian Referral Guidelines
Medline (with guideline filter)
Sources of systematic reviews and meta-analyses
Systematic reviews
Protocols
Database of Abstracts of Reviews of Effects
Medline (with systematic review filter)
EMBASE (with systematic review filter)
Sources of health technology assessments and economic appraisals
NIHR Health Technology Assessment programme
NHS Economic Evaluations
Health Technology Assessments
Canadian Agency for Drugs and Technologies in Health
International Network of Agencies for Health Technology Assessment
Sources of randomized controlled trials
Central Register of Controlled Trials
Medline (with randomized controlled trial filter)
EMBASE (with randomized controlled trial filter)
Sources of evidence based reviews and evidence summaries
DynaMed
Central Services Agency COMPASS Therapeutic Notes
Sources of national policy
Health Management Information Consortium (HMIC)
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