Background: Much is still unclear about the mechanisms underlying the course of major depressive disorder (MDD). This study aimed to identify risk factors that predict a poor prognosis of MDD while taking into consideration its chronicity at baseline. Methods: In patients with MDD (n = 767), we examined whether baseline clinical factors, sociodemographics, childhood trauma, personality and life events predicted the 4-year course (i.e. sustained recovery, temporary recovery and chronic course) of MDD. Baseline chronicity of MDD was taken into account by testing whether associations were different for patients with nonchronic versus chronic MDD at baseline. Results: In patients with nonchronic MDD at baseline, 27.8% developed a chronic disorder during follow-up, whereas 53.0% of patients with chronic MDD at baseline had a persistent chronic disorder during follow-up. Severity of MDD, childhood trauma and greater age were important general risk factors for a poor prognosis, independent of MDD chronicity at baseline. In contrast, low extraversion was only important for the course of nonchronic MDD at baseline, while higher education and negative life events (in patients with high neuroticism) were only relevant for the course of chronic MDD at baseline. Conclusions: One out of 4 patients with nonchronic MDD progressed to a chronic disorder, while half of the patients with chronic MDD remained chronic during follow-up. Since several risk factors for a poor prognosis differed for patients with nonchronic and chronic MDD at baseline, treatment targets should be adjusted for current chronicity of MDD.

1.
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.
2.
Hasin DS, Goodwin RD, Stinson FS, Grant BF: Epidemiology of major depressive disorder: results froth the National Epidemiologic Survey on Alcoholism and Related Conditions. Arch Gen Psychiatry 2005;62:1097-1106.
3.
Judd LL, Akiskal HS, Zeller PJ, Paulus M, Leon AC, Maser JD, Endicott J, Coryell W, Kunovac JL, Mueller TI, Rice JP, Keller MB: Psychosocial disability during the long-term course of unipolar major depressive disorder. Arch Gen Psychiatry 2000;57:375-380.
4.
Wittchen HU, Jacobi F, Rehm J, Gustavsson A, Svensson M, Jönsson B, Olesen J, Allgulander C, Alonso J, Faravelli C, Fratiglioni L, Jennum P, Lieb R, Maercker A, Van Os J, Preisig M, Salvador-Carulla L, Simon R, Steinhausen HC: The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol 2011;21:655-679.
5.
Rush AJ, Laux G, Giles DE, Jarret RB, Weissenburger J, Feldman-Koffler F, Stone L: Clinical characteristics of outpatients with chronic major depression. J Affect Disord 1995;34:25-32.
6.
Judd LL, Akiskal HS, Maser JD, Zeller PJ, Endicott J, Coryell W, Paulus MP, Kunovac JL, Leon AC, Mueller TI, Rice JA, Keller MB: A prospective 12-year study of subsyndromal and syndromal depressive symptoms in unipolar major depressive disorders. Arch Gen Psychiatry 1998;55:694-700.
7.
Spijker J, De Graaf R, Bijl RV, Beekman AT, Ormel J, Nolen WA: Duration of major depressive episodes in the general population: results from The Netherlands Mental Health Survey and Incidence Study (NEMESIS). Br J Psychiatry 2002;181:208-213.
8.
Satyanarayana S, Enns MW, Cox BJ, Sareen J: Prevalence and correlates of chronic depression in the Canadian community health survey: mental health and well-being. Can J Psychiatry 2009;54:389-398.
9.
Rubio JM, Markowitz JC, Alegria A, Perez-Fuentes G, Liu SM, Lin KH, Blanco C: Epidemiology of chronic and non-chronic major depressive disorder: results from the national epidemiologic survey on alcohol and related conditions. Depress Anxiety 2011;28:622-631.
10.
Ramana R, Paykel ES, Cooper Z, Hayhurst H, Saxty M, Surtees PG: Remission and relapse in major depression: a two-year prospective follow-up study. Psychol Med 1995;25:1161-1170.
11.
Spijker J, Bijl RV, De Graaf R, Nolen WA: Determinants of poor 1-year outcome of DSM-III-R major depression in the general population: results from the Netherlands Mental Health Survey and Incidence Study (NEMESIS). Acta Pychiatr Scand 2000;103:122-130.
12.
Rhebergen D, Lamers F, Spijker J, De Graaf R, Beekman AT, Penninx BW: Course trajectories of unipolar depressive disorders identified by latent class growth analysis. Psychol Med 2012;42:1383-1396.
13.
Rhebergen D, Beekman ATF, De Graaf R, Nolen WA, Spijker J, Hoogendijk WJ, Penninx BWJH: The three-year naturalistic course of major depressive disorder, dysthymic disorder and double depression. J Affect Disord 2009;115:450-459.
14.
Boschloo L, Vogelzangs N, Van den Brink W, Smit JH, Veltman DJ, Beekman AT, Penninx BW: Alcohol use disorders and the course of depressive and anxiety disorders. Br J Psychiatry 2012;200:476-484.
15.
Wiersma JE, Hovens JG, Van Oppen P, Giltay EJ, Van Schaik DJ, Beekman AT, Penninx BW: The importance of childhood trauma and childhood life events for chronicity of depression in adults. J Clin Psychiatry 2009;70:983-989.
16.
Robison EJ, Shankman SA, McFarland BR: Independent associations between personality traits and clinical characteristics of depression. J Nerv Ment Dis 2009;197:476-483.
17.
Friis RH, Wittchen H-U, Pfister H, Lieb R: Life events and changes in the course of depression in young adults. Eur Psychiatry 2002;17:241-253.
18.
Kendler KS, Kuhn J, Prescott CA: The interrelatedness of neuroticism, sex, and stressful life events in the prediction of episodes of major depression. Am J Psychiatry 2004;161:631-636.
19.
Kendler KS, Walters EE, Kessler RC: The prediction of length of major depressive episode: results from an epidemiological sample of female twins. Psychol Med 1997;27:107-117.
20.
Spijker J, De Graaf R, Bijl RV, Beekman ATF, Ormel J, Nolen WA: Determinants of persistence of major depressive episodes in the general population. Results from the Netherlands Mental Health Survey and Incidence Study (NEMESIS). J Affect Disord 2004;81:231-240.
21.
Kessler RC, Andrews G, Colpe LJ, Hiripi E, Mroczek DK, Normand SL, Walters EE, Zaslavsky AM: Short screening scales to monitor population prevalences and trends in non-specific psychological distress. Psychol Med 2002;32:959-976.
22.
Penninx BW, Beekman AT, Smit JH, Zitman FG, Nolen WA, Spinhoven P, Cuijpers P, De Jong PJ, Van Marwijk HW, Assendelft WJ, Van Der Meer K, Verhaak P, Wensing M, De Graaf R, Hoogendijk WJ, Ormel J, Van Dyck R; NESDA Research Consortium: The Netherlands Study of Depression and Anxiety (NESDA): rationale, objectives and methods. Int J Methods Psychiatr Res 2008;17:121-140.
23.
Lamers F, Hoogendoorn A, Smit J, Van Dyck R, Zitman FG, Nolen WA, Penninx BW: Sociodemographic and psychiatric determinants of attrition in the Netherlands Study of Depression and Anxiety (NESDA). Compr Psychiatry 2012;53:63-70.
24.
Wittchen HU, Robins LN, Cottler LB, Sartorius N, Burke JD, Regier D: Cross-cultural feasibility, reliability and sources of variance of the Composite International Diagnostic Interview (CIDI). The Multicentre WHO/ADAMHA Field Trials. Br J Psychiatry 1991;159:645-653, 658.
25.
Rush AJ, Gullion CM, Basco MR, Jarret RB, Trivedi MH: The Inventory of Depressive Symptomatology (IDS): psychometric properties. Psychol Med 1996;26:477-486.
26.
Lyketsos CG, Nestadt G, Cwi J, Heithoff K, Eaton WW: The lifechart method to describe the course of psychopathology. Int J Methods Psychiatr Res 1994;4:143-155.
27.
Wiersma JE, Van Oppen P, Van Schaik DJ, Van der Does AJ, Beekman AT, Penninx BW: Psychological characteristics of chronic depression: a longitudinal cohort study. J Clin Psychiatry 2011;72:288-294.
28.
World Health Organization Collaborating Centre for Drug Statistics Methodology: Anatomical Therapeutic Chemical (ATC) Classification. Geneva, World Health Organization, 2007.
29.
Costa PTJ, McCrae RR: Domains and facets: hierarchical personality assessment using the revised NEO personality inventory. J Pers Assess 1995;64:21-50.
30.
Brugha T, Bebbington P, Tennant C, Hurry J: The List of Threatening Experiences: a subset of 12 life event categories with considerable long-term contextual threat. Psychol Med 1985;15:189-194.
31.
Paykel ES, Ramana R, Cooper Z, Hayhurst H, Kerr J, Barockka A: Residual symptoms after partial remission: an important outcome in depression. Psychol Med 1995;25:1171-1180.
32.
Paykel ES: Partial remission, residual symptoms, and relapse in depression. Dialogues Clin Neurosci 2008;10:431-437.
33.
Karsten J, Hartman CA, Smit JH, Zitman FG, Beekman ATF, Cuijpers P, Van der Does AJW, Ormel J, Nolen WA, Penninx BWJH: Psychiatric history and subthreshold symptoms as predictors of the occurrence of depressive or anxiety disorder within 2 years. Br J Psychiatry 2011;198:206-212.
34.
Fava GA, Kellner R: Staging: a neglected dimension in psychiatric classification. Acta Psychiatr Scand 1993;87:225-230.
35.
McGorry PD, Hickie IB, Yung AR, Pantelis C, Jackson HJ: Clinical staging of psychiatric disorders: a heuristic framework for choosing earlier, safer and more effective interventions. Aust NZ J Psychiatry 2006;40:616-622.
36.
Fava GA, Tossani E: Prodromal stage of major depression. Early Interv Psychiatry 2007;1:9-18.
37.
Hetrick SE, Parker AG, Hickie IB, Purcell R, Yung AR, McGorry PD: Early identification and intervention in depressive disorders: towards a clinical staging model. Psychother Psychosom 2008;77:263-270.
38.
Cosci F, Fava GA: Staging of mental disorders: systematic review. Psychother Psychosom 2013;82:20-34.
39.
Hovens JG, Wiersma JE, Giltay EJ, Van Oppen P, Spinhoven P, Penninx BW, Zitman FG: Childhood life events and childhood trauma in adult patients with depressive, anxiety and comorbid disorders vs. controls. Acta Psychiatr Scand 2010;122:66-74.
40.
Lamers F, De Jonge P, Nolen WA, Smit JH, Zitman FG, Beekman ATF, Penninx BWJH: Identifying depressive subtypes in a large cohort study: results from the Netherlands Study of Depression and Anxiety (NESDA). J Clin Psychiatry 2010;71:1582-1589.
41.
Lamers F, Van Oppen P, Comijs HC, Smit JH, Spinhoven P, Van Balkom AJ, Nolen WA, Zitman FG, Beekman AT, Penninx BW: Comorbidity patterns of anxiety and depressive disorders in a large cohort study: the Netherlands Study of Depression and Anxiety (NESDA). J Clin Psychiatry 2011;72:341-348.
42.
Babor TF, Fuente JRDI, Saunders J, Grant M; The Alcohol Use Disorders Identification Test: Guidelines for Use in Primary Health Care. Geneva, World Health Organization, 1992.
43.
Boschloo L, Vogelzangs N, Smit JH, Van den Brink W, Veltaman DJ, Beekman AT, Penninx BW: The performance of the Alcohol Use Disorder Identification Test (AUDIT) in detecting alcohol abuse and dependence in a population of depressed or anxious persons. J Affect Disord 2010;126:441-446.
44.
Riso LP, Newman CF: Cognitive therapy for chronic depression. J Clin Psychol 2003;59:817-831.
45.
Tang TZ, DeRubeis RJ, Hollon SD, Amsterdam J, Shelton R, Schalet B: Personality change during depression treatment. Arch Gen Psychiatry 2009;66:1322-1330.
46.
Ormel J, Oldehinkel AJ, Brilman EI: The interplay and etiological continuity of neuroticism, difficulties, and life events in the etiology of major and subsyndromal, first and recurrent depressive disorders. Am J Psychiatry 2001;158:885-891.
47.
Ormel J, De Jong A: On vulnerability to common mental disorders: an evidence-based plea for a developmental perspective; in Tansella M, Thronicroft G (eds): Common Mental Disorders in Primary Care. London, Routledge, 1999, pp 34-52.
48.
American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed 4. Washington, American Psychiatric Association, 2000.
49.
Fava GA, Tomba E: New modalities of assessment and treatment planning in depression: the sequential approach. CNS Drugs 2010;24:453-465.
50.
Tomba E: Nowhere patients. Psychother Psychosom 2012;81:69-72.
51.
Fava GA: Modern psychiatric treatment: a tribute to Thomas Detre, MD (1924-2011). Psychother Psychosom 2013;82:1-7.
52.
Thase ME, Rush AJ: When at first you don't succeed: sequential strategies for antidepressant nonresponders. J Clin Psychiatry 1997;58:23-29.
53.
Souery D, Amsterdam J, de Montigny C, Lecrubier Y, Montgomery S, Lipp O, Racagni G, Zohar J, Mendlewic J: Treatment resistant depression: methodological overview and operational criteria. Eur Neuropsychoparmacol 1999;9:83-91.
54.
Fava M: Diagnosis and definition of treatment-resistant depression. Biol Psychiatry 2003;53:649-659.
55.
Fekadu A, Wooderson S, Donaldson C, Markopoulou K, Masterson B, Poon L, Cleare AJ: A multidimensional tool to quantify treatment resistance in depression: the Maudsley staging method. J Clin Psychiatry 2009;70:177-184.
56.
Fekadu A, Wooderson SC, Markopoulou K, Cleare AJ: The Maudsley Staging Method for treatment-resistant depression: prediction of longer-term outcome and persistence of symptoms. J Clin Psychiatry 2009;70:952-957.
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