Current Psychiatry Reports

, Volume 7, Issue 6, pp 413–420

Predictive effects of previous episodes on the risk of recurrence in depressive and bipolar disorders

  • Lars Vedel Kessing
  • Per Kragh Andersen


Findings from several studies have suggested that the risk of recurrence increases with the number of previous episodes in depressive and bipolar disorders. However, a comprehensive and critical review of the literature published during the past century shows that in several previous studies, a progressive course of episodes may have been falsely shown, mainly because of various kinds of biases and because these studies have not considered individual heterogeneity in their analyses. Nevertheless, four recent studies, including two nationwide register studies from Denmark, a prospective 15-year multicenter study from the United States, and a prospective lifelong study from Zurich, Switzerland, generally have taken these drawbacks and pitfalls into account in the design and handling of data. In all four studies, an effect of episodes was found in depressive (four studies) and bipolar (three studies) disorders. It is concluded that the average risk of recurrence increases with the number of episodes in depressive and in bipolar affective disorders. Nevertheless, the course of illness in unipolar and bipolar disorders is heterogeneous, and the effect of previous episodes and its interrelation with other risk factors on the risk of relapse and recurrence warrants additional research.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Post RM: Transduction of psychosocial stress into the neurobiology of recurrent affective disorder. Am J Psychiatry 1992, 149:999–1010.PubMedGoogle Scholar
  2. 2.
    Kraepelin E: Manic-Depressive Insanity and Paranoia. Edinburgh: Livingstone; 1921.Google Scholar
  3. 3.
    Angst J, Weis P: Periodicity of depressive psychoses. In In Proceedings of the Fifth International Congress of the Collegium Internationale. Neuropsychopharmacologicum. Edited by Washington DCH, Brill JO, Cole P, et al. Amsterdam: Excerpta Medica Foundation; 1967:703–710.Google Scholar
  4. 4.
    Swift HM: The prognosis of recurrent insanity of the manic depressive type. Am J Insanity 1907, 64:311–326.Google Scholar
  5. 5.
    MacDonald JB: Prognosis in manic-depressive insanity. J Nerv Ment Dis 1918, 47:20–30.CrossRefGoogle Scholar
  6. 6.
    Lewis A: Manic-depressive psychosis. J Ment Sci 1936, 82:488–558.Google Scholar
  7. 7.
    Slater E: Zur Periodik des manisch-depressiven Irreseins. Z Ges Neurol Psychiatr 1938, 162:794–801.Google Scholar
  8. 8.
    Lundquist G: Prognosis and course in manic-depressive psychoses. A follow-up study of 319 first admissions. Acta Psychiatr Neurol 1945, (Suppl35)1–96.Google Scholar
  9. 9.
    Perris C, d’Elia G: A study of bipolar (manic-depressive) and unipolar recurrent depressive psychoses. IX. Therapy and prognosis. Acta Psychiatr Scand Suppl 1966, 194:153–171.PubMedGoogle Scholar
  10. 10.
    Bratfos O, Haug JO: The course of manic-depressive psychosis. A follow up investigation of 215 patients. Acta Psychiatr Scand 1968, 44:89–112.PubMedGoogle Scholar
  11. 11.
    Grof P, Angst J, Haines A: The clinical course of depression: practical issues. In Classification and Prediction of Outcome of Depression (Symposia Medica Hoechst 8). Edited by Angst J. Stuttgart: Schattauer Verlag; 1973:140–155.Google Scholar
  12. 12.
    Angst J, Baastrup P, Grof P, et al.: The course of monopolar depression and bipolar psychoses. Psychiatr Neurol Neurochir 1973, 76:489–500.PubMedGoogle Scholar
  13. 13.
    Zis AP, Grof P, Webster MA, Goodwin FK: The cyclicity of affective disorders and its modifications by drugs. Psychopharmacol Bull 1980, 16:47–49.PubMedGoogle Scholar
  14. 14.
    Taschev T: The course and prognosis of depression on the basis of 652 patients deceased. In Classification and Prediction of Outcome of Depression (Symposia Medica Hoechst 8). Edited by Angst J. Stuttgart: Schattauer Verlag; 1973:157–172.Google Scholar
  15. 15.
    Feighner JP, Robins E, Guze SB, et al.: Diagnostic criteria for use in psychiatric research. Arch Gen Psychiatry 1972, 26:57–63.PubMedGoogle Scholar
  16. 16.
    Winokur G: The Iowa 500: heterogeneity and course in manic-depressive illness (bipolar). Compr Psychiatry 1975, 16:125–131.PubMedCrossRefGoogle Scholar
  17. 17.
    Saran BM: Lithium. Lancet 1969, 1:1208–1209.PubMedCrossRefGoogle Scholar
  18. 18.
    Angst J: Course of affective disorders. In Handbook of Biological Psychiatry. Part 5. Brain Mechanisms and Abnormal Behavior. Edited by Sachar EJ. New York: Marcel Dekker; 1981: 225–242.Google Scholar
  19. 19.
    Gonzales LR, Lewinsohn PM, Clarke GN: Longitudinal followup of unipolar depressives: an investigation of predictors of relapse. J Consult Clin Psychol 1985, 53:461–469.PubMedCrossRefGoogle Scholar
  20. 20.
    Lee AS, Murray RM: The long-term outcome of Maudsley depressives. Br J Psychiatry 1988, 153:741–751.PubMedGoogle Scholar
  21. 21.
    Kiloh LG, Andrews G, Neilson M: The long-term outcome of depressive illness. Br J Psychiatry 1988, 153:752–757.PubMedGoogle Scholar
  22. 22.
    Fukuda K, Etoh T, Iwadate T, Ishii A: The course and prognosis of manic-depressive psychosis: a quantitative analysis of episodes and intervals. Tohoku J Exp Med 1983, 139:299–307.PubMedCrossRefGoogle Scholar
  23. 23.
    Faravelli C, Ambonetti A, Pallanti S, Pazzagli A: Depressive relapses and incomplete recovery from index episode. Am J Psychiatry 1986, 143:888–891.PubMedGoogle Scholar
  24. 24.
    Lehmann HE, Fenton FR, Deutsch M, et al.: An 11-year followup study of 110 depressed patients. Acta Psychiatr Scand 1988, 78:57–65.PubMedGoogle Scholar
  25. 25.
    Endicott J, Spitzer RL: A diagnostic interview: the schedule for affective disorders and schizophrenia. Arch Gen Psychiatry 1978, 35:837–844.PubMedGoogle Scholar
  26. 26.
    Keller MB, Lavori PW, Friedman B, et al.: The Longitudinal Interval Follow-up Evaluation. A comprehensive method for assessing outcome in prospective longitudinal studies. Arch Gen Psychiatry 1987, 44:540–548.PubMedGoogle Scholar
  27. 27.
    Spitzer RL, Endicott J, Robins E: Research diagnostic criteria: rationale and reliability. Arch Gen Psychiatry 1978, 35:773–782.PubMedGoogle Scholar
  28. 28.
    Keller MB, Shapiro RW, Lavori PW, Wolfe N: Relapse in major depressive disorder: analysis with the life table. Arch Gen Psychiatry 1982, 39:911–915.PubMedGoogle Scholar
  29. 29.
    Keller MB, Lavori PW, Lewis CE, Klerman GL: Predictors of relapse in major depressive disorder. JAMA 1983, 250:3299–3304.PubMedCrossRefGoogle Scholar
  30. 30.
    Winokur G, Coryell W, Keller M, et al.: A prospective follow-up of patients with bipolar and primary unipolar affective disorder. Arch Gen Psychiatry 1993, 50:457–465.PubMedGoogle Scholar
  31. 31.
    Lavori PW, Keller MB, Mueller TI, et al.: Recurrence after recovery in unipolar MDD: An observational follow-up study of clinical predictors and somatic treatment as a mediating factor. Int J Methods Psychiatr Research 1994, 4:211–229.Google Scholar
  32. 32.
    Mueller TI, Leon AC, Keller MB, et al.: Recurrence after recovery from major depressive disorder during 15 years of observational follow-up. Am J Psychiatry 1999, 156:1000–1006.PubMedGoogle Scholar
  33. 33.
    Roy-Byrne P, Post RM, Uhde TW, et al.: The longitudinal course of recurrent affective illness: life chart data from research patients at the NIMH. Acta Psychiatr Scand Suppl 1985, 317:1–34.PubMedGoogle Scholar
  34. 34.
    Winokur G, Coryell W, Akiskal HS, et al.: Manic-depressive (bipolar) disorder: the course in light of a prospective tenyear follow-up of 131 patients. Acta Psychiatr Scand 1994, 89:102–110.PubMedGoogle Scholar
  35. 35.
    Maj M, Veltro F, Pirozzi R, et al.: Pattern of recurrence of illness after recovery from an episode of major depression: a prospective study. Am J Psychiatry 1992, 149:795–800.PubMedGoogle Scholar
  36. 36.
    Goldberg JF, Harrow M, Grossman LS: Recurrent affective syndromes in bipolar and unipolar mood disorders at followup. Br J Psychiatry 1995, 166:382–385.PubMedGoogle Scholar
  37. 37.
    Ramana R, Paykel ES, Cooper Z, et al.: Remission and relapse in major depression: a two-year prospective follow-up study. Psychol Med 1995, 25:1161–1170.PubMedCrossRefGoogle Scholar
  38. 38.
    Flint AJ, Rifat SL: The effect of treatment on the two-year course of late-life depression. Br J Psychiatry 1997, 170:268–272.PubMedGoogle Scholar
  39. 39.
    Lin EH, Katon WJ, VonKorff M, et al.: Relapse of depression in primary care. Rate and clinical predictors. Arch Fam Med 1998, 7:443–449.PubMedCrossRefGoogle Scholar
  40. 40.
    Cusin C, Serretti A, Lattuada E, et al.: Impact of clinical variables on illness time course in mood disorders. Psychiatry Res 2000, 97:217–227.PubMedCrossRefGoogle Scholar
  41. 41.
    Riise T, Lund A: Prognostic factors in major depression: a long-term follow-up study of 323 patients. J Affect Disord 2001, 65:297–306.PubMedCrossRefGoogle Scholar
  42. 42.
    Limosin F, Loze JY, Zylberman-Bouhassira M, et al.: The course of depressive illness in general practice. Can J Psychiatry 2004, 49:119–123.PubMedGoogle Scholar
  43. 43.
    Flint AJ, Rifat SL: Maintenance treatment for recurrent depression in late life. A four-year outcome study. Am J Geriatr Psychiatry 2000, 8:112–116.PubMedCrossRefGoogle Scholar
  44. 44.
    Kanai T, Takeuchi H, Furukawa TA, et al.: Time to recurrence after recovery from major depressive episodes and its predictors. Psychol Med 2003, 33:839–845.PubMedCrossRefGoogle Scholar
  45. 45.
    Melartin TK, Rytsala HJ, Leskela US, et al.: Severity and comorbidity predict episode duration and recurrence of DSM-IV major depressive disorder. J Clin Psychiatry 2004, 65:810–819.PubMedCrossRefGoogle Scholar
  46. 46.
    Kessing LV, Andersen PK, Mortensen PB, Bolwig TG: Recurrence in affective disorder. I. Case register study. Br J Psychiatry 1998, 172:23–28.PubMedGoogle Scholar
  47. 47.
    Kessing LV, Hansen MG, Andersen PK: Course of illness in depressive and bipolar disorders. Naturalistic study, 1994–1999. Br J Psychiatry 2004, 185:372–377. A recent register study including all Danish patients hospitalized with a diagnosis of primary affective disorder at their first admission ever and including frailty methods in the analyses.PubMedCrossRefGoogle Scholar
  48. 48.
    Kessing LV, Hansen MG, Andersen PK, Angst J: The predictive effect of episodes on the risk of recurrence in depressive and bipolar disorders - a life-long perspective. Acta Psychiatr Scand 2004, 109:339–344. A 30-to 40-year prospective follow-up study of 186 patients with unipolar disorder and 220 patients with bipolar disorder from Switzerland and including frailty methods in the analyses.PubMedCrossRefGoogle Scholar
  49. 49.
    Goldberg JF, Harrow M, Grossman LS: Course and outcome in bipolar affective disorder: a longitudinal follow-up study. Am J Psychiatry 1995, 152:379–384.PubMedGoogle Scholar
  50. 50.
    Gitlin MJ, Swendsen J, Heller TL, Hammen C: Relapse and impairment in bipolar disorder. Am J Psychiatry 1995, 152:1635–1640.PubMedGoogle Scholar
  51. 51.
    Tohen M, Waternaux CM, Tsuang MT: Outcome in Mania. A 4-year prospective follow-up of 75 patients utilizing survival analysis. Arch Gen Psychiatry 1990, 47:1106–1111.PubMedGoogle Scholar
  52. 52.
    Coryell W, Endicott J, Keller MB: Predictors of relapse into major depressive disorder in a nonclinical population. Am J Psychiatry 1991, 148:1353–1358.PubMedGoogle Scholar
  53. 53.
    Kendler KS, Thornton LM, Gardner CO: Genetic risk, number of previous depressive episodes, and stressful life events in predicting onset of major depression. Am J Psychiatry 2001, 158:582–586. An elegant study showing that the association between stressful life events and the risk for major depression declines as the number of depressive episodes increases.PubMedCrossRefGoogle Scholar
  54. 54.
    Paskind HA: Manic-depressive psychosis in private practice. Length of the attack and length of the interval. Arch Neurol Psychiatry 1930, 23:789–794.Google Scholar
  55. 55.
    Watts CAH: The incidence and prognosis of endogenous depression. Bri Med J 1956, 1:1392–1397.Google Scholar
  56. 56.
    Lewinsohn PM, Zeiss AM, Duncan EM: Probability of relapse after recovery from an episode of depression. J Abnorm Psychol 1989, 98:107–116.PubMedCrossRefGoogle Scholar
  57. 57.
    Haghighat R: Lifelong development of risk of recurrence in depressive disorders. J Affect Disord 1996, 41:141–147.PubMedCrossRefGoogle Scholar
  58. 58.
    Kessing LV: Course and cognitive outcome in major affective disorder [thesis]. Copenhagen: University of Copenhagen; 2001. A doctorial thesis providing a comprehensive review of the literature and methodological aspects of analyses of the course of illness in affective disorders.Google Scholar
  59. 59.
    Kessing LV, Olsen EW, Andersen PK: Recurrence in affective disorder: analyses with frailty models. Am J Epidemiol 1999, 149:404–411.PubMedGoogle Scholar
  60. 60.
    Clayton DG, Cuzick J: Multivariate generalizations of the proportional hazards model (with discussion). J Roy Statist Soc Ser 1985, 148:82–117.CrossRefGoogle Scholar
  61. 61.
    Hougaard P, Harvald B, Holm NV: Measuring the similarities between the life times of Danish twins born 1881–1930. J Amer Statist Assoc 1992, 87:17–24.CrossRefGoogle Scholar
  62. 62.
    Andersen PK, Borgan Ø, Gill RD, Keiding N: Statistical Models Based on Counting Processes. New York, 1993.Google Scholar
  63. 63.
    Lin DY, Sun WZ, Ying Z: Nonparametric estimation of the gap time distribution for serial events with censored data. Biometrika 1999, 86:59–70.CrossRefGoogle Scholar
  64. 64.
    Pena EA, Strawderman RL, Hollander M: Nonparametric estimation with recurrent event data. J Am Stat Assoc 2001, 96:1299–1304.CrossRefGoogle Scholar
  65. 65.
    Aalen OO, Fosen J, Weedon-Fekjaer H, et al.: Dynamic analysis of multivariate failure time data. Biometrics 2004, 60:764–773.PubMedCrossRefGoogle Scholar
  66. 66.
    Solomon DA, Keller MB, Leon AC, et al.: Multiple recurrences of major depressive disorder. Am J Psychiatry 2000, 157:229–233. A 10-year prospective multicenter naturalistic study from US including 318 subjects with unipolar major depressive disorder and using mixed-effects, grouped-time survival analyses to account for individual heterogeneity in the course of illness.PubMedCrossRefGoogle Scholar
  67. 67.
    Solomon DA, Leon AC, Mueller TI, et al.: DR. SOLOMON and colleagues reply. Am J Psychiatry 2001, 158:5.CrossRefGoogle Scholar
  68. 68.
    Kessing LV, Andersen PK: Recurrence of affective disorder. Am J Psychiatry 2001, 158:819–820.PubMedCrossRefGoogle Scholar
  69. 69.
    Munk-Jorgensen P, Fink P, Brevik JI, et al.: Psychiatric morbidity in primary public health care: a multicentre investigation. Part II. Hidden morbidity and choice of treatment. Acta Psychiatr Scand 1997, 95:6–12.PubMedGoogle Scholar
  70. 70.
    Coryell W, Endicott J, Winokur G, et al.: Characteristics and significance of untreated major depressive disorder. Am J Psychiatry 1995, 152:1124–1129.PubMedGoogle Scholar
  71. 71.
    Cohen P, Cohen J: The clinician’s illusion. Arch Gen Psychiatry 1984, 41:1178–1182.PubMedGoogle Scholar
  72. 72.
    Mortensen PB: The untapped potential of case registers and record-linkage studies in psychiatric epidemiology. Epidemiol Rev 1995, 17:205–209.PubMedGoogle Scholar
  73. 73.
    Bromet EJ, Dunn LO, Connell MM, et al.: Long-term reliability of diagnosing lifetime major depression in a community sample. Arch Gen Psychiatry 1986, 43:435–440.PubMedGoogle Scholar
  74. 74.
    Rice JP, Rochberg N, Endicott J, et al.: Stability of psychiatric diagnoses. An application to the affective disorders. Arch Gen Psychiatry 1992, 49:824–830.PubMedGoogle Scholar
  75. 75.
    Kendler KS, Neale MC, Kessler RC, et al.: The lifetime history of major depression in women. Reliability of diagnosis and heritability. Arch Gen Psychiatry 1993, 50:863–870.PubMedGoogle Scholar
  76. 76.
    Kessing LV: Recurrence in affective disorder. II. Effect of age and gender. Br J Psychiatry 1998, 172:29–34.PubMedCrossRefGoogle Scholar
  77. 77.
    Judd LL, Paulus MJ, Schettler PJ, et al.: Does incomplete recovery from first lifetime major depressive episode herald a chronic course of illness? Am J Psychiatry 2000, 157:1501–1504.PubMedCrossRefGoogle Scholar
  78. 78.
    Kennedy N, Paykel ES: Residual symptoms at remission from depression: impact on long-term outcome. J Affect Disord 2004, 80:135–144.PubMedCrossRefGoogle Scholar
  79. 79.
    MacQueen GM, Young LT, Robb JC, et al.: Effect of number of episodes on wellbeing and functioning of patients with bipolar disorder. Acta Psychiatr Scand 2000, 101:374–381.PubMedCrossRefGoogle Scholar
  80. 80.
    Kessing LV, Andersen PK: Does the risk of developing dementia increase with the number of episodes in patients with depressive disorder and in patients with bipolar disorder? J Neurol Neurosurg Psychiatry 2004, 75:1662–1666.PubMedCrossRefGoogle Scholar
  81. 81.
    Duman RS, Heninger GR, Nestler EJ: A molecular and cellular theory of depression. Arch Gen Psychiatry 1997, 54:597–606.PubMedGoogle Scholar
  82. 82.
    Kendler KS, Thornton LM, Gardner CO: Stressful life events and previous episodes in the etiology of major depression in women: an evaluation of the "kindling" hypothesis. Am J Psychiatry 2000, 157:1243–1251.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2005

Authors and Affiliations

  • Lars Vedel Kessing
    • 1
  • Per Kragh Andersen
    • 1
  1. 1.Department of PsychiatryUniversity Hospital of Copenhagen, RigshospitaletCopenhagen ØDenmark

Personalised recommendations