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Major Depressive Disorder

  • Chapter
The Medical Basis of Psychiatry

Abstract

Major depressive disorder or “unipolar depression” is a common condition likely related to several etiologies. Recent research has focused on the biological underpinnings of major depressive disorder as well as treatment advances, involving both pharmacotherapy and psychotherapy. In this chapter, the epidemiology, clinical picture, biological theories regarding etiology, clinical presentation in primary care and mental health settings, and treatment of major depressive disorder are reviewed. Advances in genetic approaches to understanding the pathogenesis of major depressive disorder will likely result in better and more precise treatments in the future.

The term “unipolar depression” evolved from the concept of a primary affective disorder. Primary affective disorder referred to patients whose first psychiatric disorder was depression and who did not evidence manic or bipolar symptoms. Support for the classification of primary affective disorder derived from the classic study of Cassidy et al (1), and symptoms differentiating depressed patients from controls formed the basis of the disorder. Symptoms which occurred in more than 50% of depressed patients included reduced energy, impaired concentration, anorexia, initial insomnia, loss of interest, difficulty starting activities, worrying, subjective agitation, slowed thinking, difficulty making decisions, terminal insomnia, suicidal ideation or plans, weight loss, tearfulness, slowed movements, irritability, and feeling one will never get well (2). These symptoms continue to form the basis for the diagnosis of depressive states.

This is a revision of a previous chapter authored by Dr. D.L. Dunner.

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Notes

  1. 1.

    Editor’s note: Brexpiprazole is an atypical antipsychotic that was approved by the FDA in 2015 as an adjunct for treatment of major depression.

References

  1. Cassidy WL, Flanagan NB, Spellman M, Cohen ME. Clinical observations in manic-depressive disease; a quantitative study of one hundred manic-depressive patients and fifty medically sick controls. J Am Med Assoc 1957;164:1535–1546.

    Article  CAS  PubMed  Google Scholar 

  2. Baker M, Dorzab J, Winokur G, Cadoret RJ. Depressive disease: classification and clinical characteristics. Compr Psychiatry 1971;12:354–365.

    Article  CAS  PubMed  Google Scholar 

  3. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry 1961;4:561–571.

    Article  CAS  PubMed  Google Scholar 

  4. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med 2001;16:606–613.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry 1979;134:382–389.

    Article  CAS  PubMed  Google Scholar 

  7. Rush AJ, Trivedi MH, Ibrahim HM, Carmody TJ, Arnow B, Klein DN, Markowitz JC, Ninan PT, Kornstein S, Manber R, Thase ME, Kocsis JH, Keller MB. The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biol Psychiatry 2003;54:573–583.

    Article  PubMed  Google Scholar 

  8. Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS, National Comorbidity Survey Replication. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 2003;289:3095–3105.

    Article  PubMed  Google Scholar 

  9. Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S, Wittchen HU, Kendler KS. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 1994;51:8–19.

    Article  CAS  PubMed  Google Scholar 

  10. Keller MB, Shapiro RW. “Double depression”: superimposition of acute depressive episodes on chronic depressive disorders. Am J Psychiatry 1982;139:438–442.

    Article  CAS  PubMed  Google Scholar 

  11. Grunebaum MF, Ellis SP, Li S, Oquendo MA, Mann JJ. Antidepressants and suicide risk in the United States, 1985–1999. J Clin Psychiatry 2004;65:1456–1462.

    Article  PubMed  Google Scholar 

  12. Isacsson G, Holmgren P, Ahlner J. Selective serotonin reuptake inhibitor antidepressants and the risk of suicide: a controlled forensic database study of 14,857 suicides. Acta Psychiatr Scand 2005;111:286–290.

    Article  CAS  PubMed  Google Scholar 

  13. Levinson DF. The genetics of depression: a review. Biol Psychiatry 2006;60:84–92.

    Article  CAS  PubMed  Google Scholar 

  14. Dalton VS, Kolshus E, McLoughlin DM. Epigenetics and depression: return of the repressed. J Affect Disord 2014;155:1–12.

    Article  PubMed  Google Scholar 

  15. Labonte B, Suderman M, Maussion G, Lopez JP, Navarro-Sánchez L, Yerko V, Mechawar N, Szyf M, Meaney MJ, Turecki G. Genome-wide methylation changes in the brains of suicide completers. Am J Psychiatry 2013;170:511–520.

    Article  PubMed  Google Scholar 

  16. Belmaker RH, Agam G. Major depressive disorder. N Engl J Med 2008;358:55–68.

    Article  CAS  PubMed  Google Scholar 

  17. Kaymak SU, Demir B, Sentürk S, Tatar I, Aldur MM, Uluğ B. Hippocampus glucocorticoids and neurocognitive functions in patients with first-episode major depressive disorders. Eur Arch Psychiatry Clin Neurosci 2010;260:217–223.

    Article  PubMed  Google Scholar 

  18. Stokes PE. The potential role for excessive cortisol induced by HPA hyperfunction in the pathogenesis of depression. Eur Neuropsychopharmacol 1995;5:77–82.

    Article  CAS  PubMed  Google Scholar 

  19. Cohen-Woods S, Craig IW, McGuffin P. The current state of play on the molecular genetics of depression. Psychol Med 2013;43:673–687.

    Article  CAS  PubMed  Google Scholar 

  20. ann het Rot M, Zarate Jr CA, Charney DS, Matthew SJ. Ketamine for depression: where do we go from here? Biol Psychiatry 2012;72:537–547.

    Article  Google Scholar 

  21. Murrough JW. Ketamine as a novel antidepressant: from synapse to behavior. Clin Pharmacol Ther 2012;91:303–309.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Gardner A, Boles RG. Beyond the serotonin hypothesis: mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders. Prog Neuropsychopharmacol Biol Psychiatry 2011;35:730–743.

    Article  CAS  PubMed  Google Scholar 

  23. Nemeroff CB. Recent advances in the neurobiology of depression. Psychopharmacol Bull 2002;36:6–23.

    PubMed  Google Scholar 

  24. Revicki DA, Simon GE, Chan K, Katon W, Heiligenstein J. Depression, health-related quality of life, and medical cost outcomes of receiving recommended levels of antidepressant treatment. J Fam Pract 1998;47:446–452.

    CAS  PubMed  Google Scholar 

  25. Garcia-Cebrian A, Gandhi P, Demyttenaere K, Peveler R. The association of depression and painful physical symptoms—a review of the European literature. Eur Psychiatry 2006;21:379–388.

    Article  CAS  PubMed  Google Scholar 

  26. Dunner DL, Fleiss JL, Fieve RR. The course of development of mania in patients with recurrent depression. Am J Psychiatry 1976;133:905–908.

    Article  CAS  PubMed  Google Scholar 

  27. Hirschfeld RM. The Mood Disorder Questionnaire: a simple, patient-rated screening instrument for bipolar disorder. Prim Care Companion J Clin Psychiatry 2002;4:9–11.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Frank E, Prien RF, Jarrett RB, Keller MB, Kupfer DJ, Lavori PW, Rush AJ, Weissman MM. Conceptualization and rationale for consensus definitions of terms in major depressive disorder. Remission, recovery, relapse, and recurrence. Arch Gen Psychiatry 1991;48:851–855.

    Article  CAS  PubMed  Google Scholar 

  29. Schulberg HC, Katon W, Simon GE, Scott CP, Rodriguez E, Imber SD, Perel J, Lave J, Houck PR, Coulehan JL. Treating major depression in primary care practice: an update for the Agency for Health Care Policy and Research Practice Guidelines. Arch Gen Psychiatry 1996;53:1121–1127.

    Article  Google Scholar 

  30. Hollon SD, Stewart MO, Strunk D. Enduring effects for cognitive behavior therapy in the treatment of depression and anxiety. Annu Rev Psychol 2006;57:285–315.

    Article  PubMed  Google Scholar 

  31. Keller MB, Gelenberg AJ, Hirschfeld RM, Rush AJ, Thase ME, Kocsis JH, Markowitz JC, Fawcett JA, Koran LM, Klein DN, Russell JM, Kornstein SG, McCullough JP, Davis SM, Harrison WM. The treatment of chronic depression, part 2: a double-blind, randomized trial of sertraline and imipramine. J Clin Psychiatry 1998;59:598–607.

    Article  CAS  PubMed  Google Scholar 

  32. Trivedi MH, Fava M, Wisniewski SR, Thase ME, Quitkin F, Warden D, Ritz L, Nierenberg AA, Lebowitz BD, Biggs MM, Luther JF, Shores-Wilson K, Rush AJ, STAR*D Study Team. Medication augmentation after the failure of SSRIs for depression. N Engl J Med 2006;354:1243–1252.

    Article  CAS  PubMed  Google Scholar 

  33. Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L, Norquist G, Howland RH, Lebowitz B, McGrath PJ, Shores-Wilson K, Biggs MM, Balasubramani GK, Fava M; STAR*D Study Team. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry 2006;163:28–40.

    Google Scholar 

  34. Cuijpers P, Berking M, Andersson G, Nierenberg AA, Warden D, Ritz L, Norquist G, Howland RH, Lebowitz B, McGrath PJ, Shores-Wilson K, Biggs MM, Balasubramani GK, Fava M, STAR*D Study Team. A meta-analysis of cognitive-behavioural therapy for adult depression, alone and in comparison with other treatments. Can J Psychiatry 2013;58:376–385.

    PubMed  Google Scholar 

  35. Cuijpers P, Geraedts AS, van Oppen P, Andersson G, Markowitz JC, van Straten A. Interpersonal psychotherapy for depression: a meta-analysis. Am J Psychiatry 2011;168:581–592.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Dimidjian S, Hollon SD, Dobson KS, Schmaling KB, Kohlenberg RJ, Addis ME, Gallop R, McGlinchey JB, Markley DK, Gollan JK, Atkins DC, Dunner DL, Jacobson NS. Randomized trial of behavioral activation, cognitive therapy, and antidepressant medication in the acute treatment of adults with major depression. J Consult Clin Psychol 2006;74:658–670.

    Article  PubMed  Google Scholar 

  37. Frank E, Kupfer DJ, Perel JM, Cornes C, Jarrett DB, Mallinger AG, Thase ME, McEachran AB, Grochocinski VJ. Three-year outcomes for maintenance therapies in recurrent depression. Arch Gen Psychiatry 1990;47:1093–1099.

    Article  CAS  PubMed  Google Scholar 

  38. Gelenberg AJ, Trivedi MH, Rush AJ, Thase ME, Howland R, Klein DN, Kornstein SG, Dunner DL, Markowitz JC, Hirschfeld RM, Keitner GI, Zajecka J, Kocsis JH, Russell JM, Miller I, Manber R, Arnow B, Rothbaum B, Munsaka M, Banks P, Borian FE, Keller MB. Randomized, placebo-controlled trial of nefazodone maintenance treatment in preventing recurrence in chronic depression. Biol Psychiatry 2003;54:806–817.

    Article  CAS  PubMed  Google Scholar 

  39. Hollon SD, DeRubeis RJ, Shelton RC, Amsterdam JD, Salomon RM, O’Reardon JP, Lovett ML, Young PR, Haman KL, Freeman BB, Gallop R. Prevention of relapse following cognitive therapy vs medications in moderate to severe depression. Arch Gen Psychiatry 2005;62:417–422.

    Article  PubMed  Google Scholar 

  40. Jacobson NS, Dobson KS, Truax PA, Addis ME, Koerner K, Gollan JK, Gortner E, Prince SE. A component analysis of cognitive-behavioral treatment for depression. J Consult Clin Psychol 1996;64:295–304.

    Article  CAS  PubMed  Google Scholar 

  41. Citrome L. Levomilnacipran for major depressive disorder: a systematic review of the efficacy and safety profile for this newly approved antidepressant—what is the number needed to treat, number needed to harm and likelihood to be helped or harmed? Int J Clin Pract 2013;67:1089–1104.

    Article  CAS  PubMed  Google Scholar 

  42. Wang SM, Han C, Lee SJ, Patkar AA, Masand PS, Pae CU. A review of current evidence for vilazodone in major depressive disorder. Int J Psychiatry Clin Pract 2013;17:160–169.

    Article  CAS  PubMed  Google Scholar 

  43. Laughren TP, Gobburu J, Temple RJ, Unger EF, Bhattaram A, Dinh PV, Fossom L, Hung HM, Klimek V, Lee JE, Levin RL, Lindberg CY, Mathis M, Rosloff BN, Wang SJ, Wang Y, Yang P, Yu B, Zhang H, Zhang L, Zineh I. Vilazodone: clinical basis for the US Food and Drug Administration’s approval of a new antidepressant. J Clin Psychiatry 2011;72:1166–1173.

    Article  CAS  PubMed  Google Scholar 

  44. Pearce EF, Murphy JA. Vortioxetine for the treatment of depression. Ann Pharmacother 2014;48:758–765.

    Article  PubMed  Google Scholar 

  45. Blumberger DM, Mulsant BH, Daskalakis ZJ. What is the role of brain stimulation therapies in the treatment of depression? Curr Psychiatry Rep 2013;15:368.

    Article  PubMed  Google Scholar 

  46. Rosa MA, Lisanby SH. Somatic treatments for mood disorders. Neuropsychopharmacology 2012;37:102–116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Avery DH, Bolte MA, Dager SR, Wilson LG, Weyer M, Cox GB, Dunner DL. Dawn simulation treatment of winter depression: a controlled study. Am J Psychiatry 1993;150:113–117.

    Article  CAS  PubMed  Google Scholar 

  48. Sackeim HA, Haskett RF, Mulsant BH, Thase ME, Mann JJ, Pettinati HM, Greenberg RM, Crowe RR, Cooper TB, Prudic J. Continuation pharmacotherapy in the prevention of relapse following electroconvulsive therapy: a randomized controlled trial. JAMA 2001;285:1299–1307.

    Article  CAS  PubMed  Google Scholar 

  49. Nemeroff CB, Mayberg HS, Krahl SE, McNamara J, Frazer A, Henry TR, George MS, Charney DS, Brannan SK. VNS therapy in treatment-resistant depression: clinical evidence and putative neurobiological mechanisms. Neuropsychopharmacology 2006;31:1345–1355.

    Article  PubMed  Google Scholar 

  50. Dunner DL, Rush AJ, Russell JM, Burke M, Woodard S, Wingard P, Allen J. Prospective, long-term, multicenter study of the naturalistic outcomes of patients with treatment-resistant depression. J Clin Psychiatry 2006;67:688–695.

    Article  PubMed  Google Scholar 

  51. Avery DH, Holtzheimer PE 3rd, Fawaz W, Russo J, Neumaier J, Dunner DL, Haynor DR, Claypoole KH, Wajdik C, Roy-Byrne P. A controlled study of repetitive transcranial magnetic stimulation in medication-resistant major depression. Biol Psychiatry 2006;59:187–194.

    Article  PubMed  Google Scholar 

  52. Shelton RC, Tollefson GD, Tohen M, Stahl S, Gannon KS, Jacobs TG, Buras WR, Bymaster FP, Zhang W, Spencer KA, Feldman PD, Meltzer HY. A novel augmentation strategy for treating resistant major depression. Am J Psychiatry 2001;158:131–134.

    Article  CAS  PubMed  Google Scholar 

  53. Nelson JC, Papakostas GI. Atypical antipsychotic augmentation in major depressive disorder: a meta-analysis of placebo-controlled randomized trials. Am J Psychiatry 2009;166:980–991.

    Article  PubMed  Google Scholar 

  54. Shelton RC, Keller MB, Gelenberg A, Dunner DL, Hirschfeld R, Thase ME, Russell J, Lydiard RB, Crits-Cristoph P, Gallop R, Todd L, Hellerstein D, Goodnick P, Keitner G, Stahl SM, Halbreich U. Effectiveness of St John’s wort in major depression: a randomized controlled trial. JAMA 2001;285:1978–1986.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Psychiatry, University of Minnesota School of Medicine, Minneapolis, MN, USA

    Barry R. Rittberg M.D. (Assistant Professor)

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  1. Barry R. Rittberg M.D.
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Correspondence to Barry R. Rittberg M.D. .

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  1. University of Minnesota School of Medicine, Minneapolis, Minnesota, USA

    S. Hossein Fatemi

  2. University of New Mexico School of Medicine Pasadena, University of Minnesota School of Medicine, California, California, USA

    Paula J. Clayton

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Rittberg, B.R. (2016). Major Depressive Disorder. In: Fatemi, S., Clayton, P. (eds) The Medical Basis of Psychiatry. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2528-5_5

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  • DOI: https://doi.org/10.1007/978-1-4939-2528-5_5

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