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Unipolar depression in adults: Continuation and maintenance treatment

Robin B Jarrett, PhD
Jeffrey Vittengl, PhD
Section Editor
Peter P Roy-Byrne, MD
Deputy Editor
David Solomon, MD


Continuation and maintenance treatment are generally indicated for patients with unipolar major depression because the illness is highly recurrent [1-3]. Standard treatments include pharmacotherapy, psychotherapy, or pharmacotherapy plus psychotherapy.

This topic reviews continuation and maintenance treatment for nonpsychotic, unipolar major depression in adults. Choosing a regimen for the initial treatment of depression and treatment of resistant depression is discussed separately, as is maintenance treatment of psychotic depression, geriatric depression, and pediatric depression.

(See "Unipolar major depression in adults: Choosing initial treatment".)

(See "Unipolar depression in adults: Treatment of resistant depression".)

(See "Unipolar major depression with psychotic features: Maintenance treatment and course of illness".)

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Literature review current through: Dec 2017. | This topic last updated: Oct 21, 2016.
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  1. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Major Depressive Disorder, third edition. Am J Psychiatry 2010; 167 (supplement):1.
  2. American Psychiatric Association: Practice Guideline for the Treatment of Patients with Major Depressive Disorder, Third Edition, 2010. http://psychiatryonline.org/guidelines.aspx (Accessed on April 17, 2012).
  3. National Institute of Health and Clinical Excellence. Depression: The treatment and management of depression in adults (updated version). National Clinical Practice Guideline 90. http://www.nice.org.uk/ (Accessed on May 19, 2012).
  4. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), American Psychiatric Association, Arlington, VA 2013.
  5. Frank E, Prien RF, Jarrett RB, et al. Conceptualization and rationale for consensus definitions of terms in major depressive disorder. Remission, recovery, relapse, and recurrence. Arch Gen Psychiatry 1991; 48:851.
  6. Rush AJ, Kraemer HC, Sackeim HA, et al. Report by the ACNP Task Force on response and remission in major depressive disorder. Neuropsychopharmacology 2006; 31:1841.
  7. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, American Psychiatric Association, Washington DC 2000.
  8. Dunlop BW, Holland P, Bao W, et al. Recovery and subsequent recurrence in patients with recurrent major depressive disorder. J Psychiatr Res 2012; 46:708.
  9. Jarrett RB, Thase ME. Comparative efficacy and durability of continuation phase cognitive therapy for preventing recurrent depression: design of a double-blinded, fluoxetine- and pill placebo-controlled, randomized trial with 2-year follow-up. Contemp Clin Trials 2010; 31:355.
  10. Deshauer D, Moher D, Fergusson D, et al. Selective serotonin reuptake inhibitors for unipolar depression: a systematic review of classic long-term randomized controlled trials. CMAJ 2008; 178:1293.
  11. Vittengl JR, Clark LA, Dunn TW, Jarrett RB. Reducing relapse and recurrence in unipolar depression: a comparative meta-analysis of cognitive-behavioral therapy's effects. J Consult Clin Psychol 2007; 75:475.
  12. Geddes JR, Carney SM, Davies C, et al. Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. Lancet 2003; 361:653.
  13. Kaymaz N, van Os J, Loonen AJ, Nolen WA. Evidence that patients with single versus recurrent depressive episodes are differentially sensitive to treatment discontinuation: a meta-analysis of placebo-controlled randomized trials. J Clin Psychiatry 2008; 69:1423.
  14. Collins PY, Patel V, Joestl SS, et al. Grand challenges in global mental health. Nature 2011; 475:27.
  15. Williams N, Simpson AN, Simpson K, Nahas Z. Relapse rates with long-term antidepressant drug therapy: a meta-analysis. Hum Psychopharmacol 2009; 24:401.
  16. Cuijpers P, Hollon SD, van Straten A, et al. Does cognitive behaviour therapy have an enduring effect that is superior to keeping patients on continuation pharmacotherapy? A meta-analysis. BMJ Open 2013; 3.
  17. Jarrett RB, Vittengl JR, Clark LA. Preventing recurrent depression. In: Adapting Cognitive Therapy for Depression: Managing Complexity and Comorbidity, Whisman MA. (Ed), Guilford Publications, New York 2008. p.132.
  18. Bockting CL, Hollon SD, Jarrett RB, et al. A lifetime approach to major depressive disorder: The contributions of psychological interventions in preventing relapse and recurrence. Clin Psychol Rev 2015; 41:16.
  19. Hirschfeld RM. Clinical importance of long-term antidepressant treatment. Br J Psychiatry Suppl 2001; 42:S4.
  20. Preventing recurrent depression: long-term treatment for major depressive disorder. Prim Care Companion J Clin Psychiatry 2007; 9:214.
  21. Nanni V, Uher R, Danese A. Childhood maltreatment predicts unfavorable course of illness and treatment outcome in depression: a meta-analysis. Am J Psychiatry 2012; 169:141.
  22. Lam RW, Kennedy SH, Grigoriadis S, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. III. Pharmacotherapy. J Affect Disord 2009; 117 Suppl 1:S26.
  23. Parikh SV, Segal ZV, Grigoriadis S, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. II. Psychotherapy alone or in combination with antidepressant medication. J Affect Disord 2009; 117 Suppl 1:S15.
  24. Anderson IM, Ferrier IN, Baldwin RC, et al. Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2000 British Association for Psychopharmacology guidelines. J Psychopharmacol 2008; 22:343.
  25. Bauer M, Pfennig A, Severus E, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders, part 1: update 2013 on the acute and continuation treatment of unipolar depressive disorders. World J Biol Psychiatry 2013; 14:334.
  26. Hollon SD, DeRubeis RJ, Shelton RC, et al. Prevention of relapse following cognitive therapy vs medications in moderate to severe depression. Arch Gen Psychiatry 2005; 62:417.
  27. Martell, CR, Addis, et al. Depression in Context: Strategies for Guided Action, W.W. Norton & Company, New York 2001.
  28. Dimidjian S, Davis KJ. Newer variations of cognitive-behavioral therapy: behavioral activation and mindfulness-based cognitive therapy. Curr Psychiatry Rep 2009; 11:453.
  29. Dobson KS, Hollon SD, Dimidjian S, et al. Randomized trial of behavioral activation, cognitive therapy, and antidepressant medication in the prevention of relapse and recurrence in major depression. J Consult Clin Psychol 2008; 76:468.
  30. Wakefield JC, Schmitz MF. Predictive validation of single-episode uncomplicated depression as a benign subtype of unipolar major depression. Acta Psychiatr Scand 2014; 129:445.
  31. Mann JJ. The medical management of depression. N Engl J Med 2005; 353:1819.
  32. Williams JM, Kuyken W. Mindfulness-based cognitive therapy: a promising new approach to preventing depressive relapse. Br J Psychiatry 2012; 200:359.
  33. Hansen R, Gaynes B, Thieda P, et al. Meta-analysis of major depressive disorder relapse and recurrence with second-generation antidepressants. Psychiatr Serv 2008; 59:1121.
  34. Reynolds CF 3rd, Frank E, Perel JM, et al. Nortriptyline and interpersonal psychotherapy as maintenance therapies for recurrent major depression: a randomized controlled trial in patients older than 59 years. JAMA 1999; 281:39.
  35. Frank E, Kupfer DJ, Perel JM, et al. Three-year outcomes for maintenance therapies in recurrent depression. Arch Gen Psychiatry 1990; 47:1093.
  36. Reynolds CF 3rd, Dew MA, Pollock BG, et al. Maintenance treatment of major depression in old age. N Engl J Med 2006; 354:1130.
  37. Guidi J, Tomba E, Fava GA. The Sequential Integration of Pharmacotherapy and Psychotherapy in the Treatment of Major Depressive Disorder: A Meta-Analysis of the Sequential Model and a Critical Review of the Literature. Am J Psychiatry 2016; 173:128.
  38. Jarrett RB, Minhajuddin A, Gershenfeld H, et al. Preventing depressive relapse and recurrence in higher-risk cognitive therapy responders: a randomized trial of continuation phase cognitive therapy, fluoxetine, or matched pill placebo. JAMA Psychiatry 2013; 70:1152.
  39. Borges S, Chen YF, Laughren TP, et al. Review of maintenance trials for major depressive disorder: a 25-year perspective from the US Food and Drug Administration. J Clin Psychiatry 2014; 75:205.
  40. Baldessarini RJ, Lau WK, Sim J, et al. Duration of initial antidepressant treatment and subsequent relapse of major depression. J Clin Psychopharmacol 2015; 35:75.
  41. Kupfer DJ, Frank E, Perel JM, et al. Five-year outcome for maintenance therapies in recurrent depression. Arch Gen Psychiatry 1992; 49:769.
  42. Anderson IM, Tomenson BM. Treatment discontinuation with selective serotonin reuptake inhibitors compared with tricyclic antidepressants: a meta-analysis. BMJ 1995; 310:1433.
  43. Anderson IM. SSRIS versus tricyclic antidepressants in depressed inpatients: a meta-analysis of efficacy and tolerability. Depress Anxiety 1998; 7 Suppl 1:11.
  44. Demyttenaere K, Adelin A, Patrick M, et al. Six-month compliance with antidepressant medication in the treatment of major depressive disorder. Int Clin Psychopharmacol 2008; 23:36.
  45. Olfson M, Marcus SC, Tedeschi M, Wan GJ. Continuity of antidepressant treatment for adults with depression in the United States. Am J Psychiatry 2006; 163:101.
  46. Velligan DI, Weiden PJ, Sajatovic M, et al. The expert consensus guideline series: adherence problems in patients with serious and persistent mental illness. J Clin Psychiatry 2009; 70 Suppl 4:1.
  47. Osterberg L, Blaschke T. Adherence to medication. N Engl J Med 2005; 353:487.
  48. Cuijpers P, Geraedts AS, van Oppen P, et al. Interpersonal psychotherapy for depression: a meta-analysis. Am J Psychiatry 2011; 168:581.
  49. Oestergaard S, Møldrup C. Optimal duration of combined psychotherapy and pharmacotherapy for patients with moderate and severe depression: a meta-analysis. J Affect Disord 2011; 131:24.
  50. Gartlehner G, Hansen RA, Morgan LC, et al. Comparative benefits and harms of second-generation antidepressants for treating major depressive disorder: an updated meta-analysis. Ann Intern Med 2011; 155:772.
  51. Glue P, Donovan MR, Kolluri S, Emir B. Meta-analysis of relapse prevention antidepressant trials in depressive disorders. Aust N Z J Psychiatry 2010; 44:697.
  52. Blackburn IM, Moore RG. Controlled acute and follow-up trial of cognitive therapy and pharmacotherapy in out-patients with recurrent depression. Br J Psychiatry 1997; 171:328.
  53. Papakostas GI, Perlis RH, Seifert C, Fava M. Antidepressant dose reduction and the risk of relapse in major depressive disorder. Psychother Psychosom 2007; 76:266.
  54. Biesheuvel-Leliefeld KE, Kok GD, Bockting CL, et al. Effectiveness of psychological interventions in preventing recurrence of depressive disorder: meta-analysis and meta-regression. J Affect Disord 2015; 174:400.
  55. Steinert C, Hofmann M, Kruse J, Leichsenring F. Relapse rates after psychotherapy for depression - stable long-term effects? A meta-analysis. J Affect Disord 2014; 168:107.
  56. Chiesa A, Serretti A. Mindfulness based cognitive therapy for psychiatric disorders: a systematic review and meta-analysis. Psychiatry Res 2011; 187:441.
  57. Beck, AT, et al. Cognitive Therapy of Depression, Guilford Press, New York 1979.
  58. Beck AT, Dozois DJ. Cognitive therapy: current status and future directions. Annu Rev Med 2011; 62:397.
  59. Jarrett RB, Kraft D, Doyle J, et al. Preventing recurrent depression using cognitive therapy with and without a continuation phase: a randomized clinical trial. Arch Gen Psychiatry 2001; 58:381.
  60. Jarrett RB, Vittengl JR, Clark LA. How much cognitive therapy, for which patients, will prevent depressive relapse? J Affect Disord 2008; 111:185.
  61. Klerman, G, et al. Interpersonal psychotherapy of depression, Basic Books, New York 1984.
  62. Markowitz JC, Weissman MM. Interpersonal psychotherapy: past, present and future. Clin Psychol Psychother 2012; 19:99.
  63. Liebowitz M, Lam RW, Lepola U, et al. Efficacy and tolerability of extended release quetiapine fumarate monotherapy as maintenance treatment of major depressive disorder: a randomized, placebo-controlled trial. Depress Anxiety 2010; 27:964.
  64. McClintock SM, Brandon AR, Husain MM, Jarrett RB. A systematic review of the combined use of electroconvulsive therapy and psychotherapy for depression. J ECT 2011; 27:236.
  65. Brakemeier EL, Merkl A, Wilbertz G, et al. Cognitive-behavioral therapy as continuation treatment to sustain response after electroconvulsive therapy in depression: a randomized controlled trial. Biol Psychiatry 2014; 76:194.
  66. Jelovac A, Kolshus E, McLoughlin DM. Relapse following successful electroconvulsive therapy for major depression: a meta-analysis. Neuropsychopharmacology 2013; 38:2467.
  67. Kellner CH, Husain MM, Knapp RG, et al. A Novel Strategy for Continuation ECT in Geriatric Depression: Phase 2 of the PRIDE Study. Am J Psychiatry 2016; 173:1110.
  68. Kedzior KK, Reitz SK, Azorina V, Loo C. Durability of the antidepressant effect of the high-frequency repetitive transcranial magnetic stimulation (rTMS) In the absence of maintenance treatment in major depression: a systematic review and meta-analysis of 16 double-blind, randomized, sham-controlled trials. Depress Anxiety 2015; 32:193.
  69. George MS, Post RM. Daily left prefrontal repetitive transcranial magnetic stimulation for acute treatment of medication-resistant depression. Am J Psychiatry 2011; 168:356.
  70. Hoffman BM, Babyak MA, Craighead WE, et al. Exercise and pharmacotherapy in patients with major depression: one-year follow-up of the SMILE study. Psychosom Med 2011; 73:127.