Hostname: page-component-586b7cd67f-t7czq Total loading time: 0 Render date: 2024-11-28T15:20:50.417Z Has data issue: false hasContentIssue false
  • English
  • Français

Diagnostic Conversion to Bipolar Disorder in Unipolar Depressed Patients Participating in Trials on Antidepressants

Published online by Cambridge University Press:  18 December 2016

J. Holmskov ,
R.W. Licht ,
K. Andersen ,
T. Bjerregaard Stage ,
F. Mørkeberg Nilsson ,
K. Bjerregaard Stage ,
J.B. Valentin ,
P. Bech  and
R. Ernst Nielsen
J. Holmskov*
Affiliation:
Institute of Clinical Health, University of Southern Denmark, Department of Psychiatry, Odense, Region of Southern Denmark, Denmark Unit for Psychiatric Research, Aalborg University Hospital, Psychiatry, Aalborg, Denmark
R.W. Licht
Affiliation:
Unit for Psychiatric Research, Aalborg University Hospital, Psychiatry, Aalborg, Denmark Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
K. Andersen
Affiliation:
Institute of Clinical Health, University of Southern Denmark, Department of Psychiatry, Odense, Region of Southern Denmark, Denmark
T. Bjerregaard Stage
Affiliation:
Clinical Pharmacology, Department of Public Health, University of Southern Denmark, Odense, Denmark
F. Mørkeberg Nilsson
Affiliation:
Psychiatric Department, Geriatric Psychiatric Unit, Psychiatric Centre Ballerup, Capital Region, Denmark
K. Bjerregaard Stage
Affiliation:
Institute of Clinical Health, University of Southern Denmark, Department of Psychiatry, Odense, Region of Southern Denmark, Denmark
J.B. Valentin
Affiliation:
Unit for Psychiatric Research, Aalborg University Hospital, Psychiatry, Aalborg, Denmark
P. Bech
Affiliation:
Psychiatric Research Unit, Psychiatric Centre North Zealand, Copenhagen University Hospital, Copenhagen, Denmark
R. Ernst Nielsen
Affiliation:
Unit for Psychiatric Research, Aalborg University Hospital, Psychiatry, Aalborg, Denmark Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
*
* Corresponding author. at: Unit for Psychiatric Research, Aalborg University Hospital, Psychiatry, Mølleparkvej 10, 9000 Aalborg, Denmark. Tel.: +45 976 436 09. E-mail address:[email protected] (J. Holmskov).
Get access

Abstract

Objective

In unipolar depressed patients participating in trials on antidepressants, we investigated if illness characteristics at baseline could predict conversion to bipolar disorder.

Method

A long-term register-based follow-up study of 290 unipolar depressed patients with a mean age of 50.8 years (SD = 11.9) participating in three randomized trials on antidepressants conducted in the period 1985–1994. The independent effects of explanatory variables were examined by applying Cox regression analyses.

Results

The overall risk of conversion was 20.7%, with a mean follow-up time of 15.2 years per patient. The risk of conversion was associated with an increasing number of previous depressive episodes at baseline, [HR 1.18, 95% CI (1.10–1.26)]. No association with gender, age, age at first depressive episode, duration of baseline episode, subtype of depression or any of the investigated HAM-D subscales included was found.

Limitations

The patients were followed-up through the Danish Psychiatric Central Research Register, which resulted in inherent limitations such as possible misclassification of outcome.

Conclusion

In a sample of middle-aged hospitalized unipolar depressed patients participating in trials on antidepressants, the risk of conversion was associated with the number of previous depressive episodes. Therefore, this study emphasizes that unipolar depressed patients experiencing a relatively high number of recurrences should be followed more closely, or at least be informed about the possible increased risk of conversion.

Keywords

Affective disordersUnipolar depressionMania and bipolar disorderCriteriaAntidepressantEpidemiology
Type
Original article
Information
European Psychiatry , Volume 40 , February 2017 , pp. 76 - 81
Copyright
Copyright © Elsevier Masson SAS 2017

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

References

Adam, D.Mental health: on the spectrum. Nature 2013; 496(7446): 416–418CrossRefGoogle ScholarPubMed
World Health Organization, The ICD-10 classification of mental and behavioural disorders: clinical descriptions and diagnostic guideline Geneva: WHO; 1992Google Scholar
American Psychiatric Association (APA) Diagnostical and statistical manual of mental disorders (DSM-5) Washington DC: American Psychiatric Association; 2013CrossRefGoogle Scholar
Goodwin, F.K.J.Jamison, K.R.Manic-depressive illness: bipolar disorders and recurrent depression 2nd ed. 2007 Oxford University Press New York [1262 p.]Google Scholar
Angst, J.Sellaro, R.Stassen, H.H.Gamma, A.Diagnostic conversion from depression to bipolar disorders: results of a long-term prospective study of hospital admissions. J Affect Disord 2005; 84(2–3):149–157CrossRefGoogle ScholarPubMed
Goldberg, J.F.Harrow, M.Whiteside, J.E.Risk for bipolar illness in patients initially hospitalized for unipolar depression. Am J Psychiatry 2001; 158(8): 1265–1270CrossRefGoogle ScholarPubMed
Fiedorowicz, J.G.Endicott, J.Leon, A.C.Solomon, D.A.Keller, M.B.Coryell, W.H.Subthreshold hypomanic symptoms in progression from unipolar major depression to bipolar disorder. Am J Psychiatry 2011; 168(1): 40–48CrossRefGoogle ScholarPubMed
Akiskal, H.S.Maser, J.D.Zeller, P.J.Endicott, J.Coryell, W.Keller, M.et al.Switching from ‘unipolar’ to bipolar II. An 11-year prospective study of clinical and temperamental predictors in 559 patients Arch Gen Psychiatry 1995; 52(2): 114–123CrossRefGoogle ScholarPubMed
Strober, M.Carlson, G.Bipolar illness in adolescents with major depression: clinical, genetic, and psychopharmacologic predictors in a three- to four-year prospective follow-up investigation. Arch Gen Psychiatry 1982; 39(5): 549–55510.1001/archpsyc.1982.04290050029007CrossRefGoogle Scholar
Rao, U.Ryan, N.D.Birmaher, B.Dahl, R.E.Williamson, D.E.Kaufman, J.et al.Unipolar depression in adolescents: clinical outcome in adulthood J Am Acad Child Adolesc Psychiatry 1995; 34(5): 566–578CrossRefGoogle ScholarPubMed
Serretti, A.Mandelli, L.Lattuada, E.Cusin, C.Smeraldi, E.Clinical and demographic features of mood disorder subtypes. Psychiatry Res 2002; 112(3): 195–21010.1016/S0165-1781(02)00227-5CrossRefGoogle ScholarPubMed
Mitchell, P.B.Malhi, G.S.Bipolar depression: phenomenological overview and clinical characteristics. Bipolar Disord 2004; 6(6): 530–53910.1111/j.1399-5618.2004.00137.xCrossRefGoogle ScholarPubMed
Mitchell, P.B.Goodwin, G.M.Johnson, G.F.Hirschfeld, R.M.Diagnostic guidelines for bipolar depression: a probabilistic approach. Bipolar Disord 2008; 10(1 Pt 2):144–152CrossRefGoogle ScholarPubMed
Benazzi, F.Clinical differences between bipolar II depression and unipolar major depressive disorder: lack of an effect of age. J Affect Disord 2003; 75(2): 191–195CrossRefGoogle ScholarPubMed
Solomon, D.A.Leon, A.C.Maser, J.D.Truman, C.J.Coryell, W.Endicott, J.et al.Distinguishing bipolar major depression from unipolar major depression with the screening assessment of depression-polarity (SAD-P) J Clin Psychiatry 2006; 67(3): 434–44210.4088/JCP.v67n0315CrossRefGoogle Scholar
Parker, G.Roy, K.Wilhelm, K.Mitchell, P.Hadzi-Pavlovic, D.The nature of bipolar depression: implications for the definition of melancholia. J Affect Disord 2000; 59(3): 217–224CrossRefGoogle ScholarPubMed
Mitchell, P.B.Wilhelm, K.Parker, G.Austin, M.P.Rutgers, P.Malhi, G.S.The clinical features of bipolar depression: a comparison with matched major depressive disorder patients. J Clin Psychiatry 2001; 62(3): 212–216 [quiz 7]CrossRefGoogle ScholarPubMed
Strober, M.Lampert, C.Schmidt, S.Morrell, W.The course of major depressive disorder in adolescents: I. Recovery and risk of manic switching in a follow-up of psychotic and nonpsychotic subtypes. J Am Acad Child Adolesc Psychiatry 1993; 32(1): 34–4210.1097/00004583-199301000-00006CrossRefGoogle Scholar
Perlis, R.H.Brown, E.Baker, R.W.Nierenberg, A.A.Clinical features of bipolar depression versus major depressive disorder in large multicenter trials. Am J Psychiatry 2006; 163(2): 225–231CrossRefGoogle ScholarPubMed
Angst, J.Felder, W.Frey, R.Stassen, H.H.The course of affective disorders. I. Change of diagnosis of monopolar, unipolar, and bipolar illness. Arch Psychiatr Nervenkr (1970) 1978; 226(1): 57–64CrossRefGoogle ScholarPubMed
Winokur, G.Wesner, R.From unipolar depression to bipolar illness: 29 who changed. Acta Psychiatr Scand 1987; 76(1): 59–63CrossRefGoogle ScholarPubMed
Benazzi, F.Akiskal, H.S.How best to identify a bipolar-related subtype among major depressive patients without spontaneous hypomania: superiority of age at onset criterion over recurrence and polarity?. J Affect Disord 2008; 107(1–3):77–88CrossRefGoogle ScholarPubMed
Takeshima, M.Oka, T.A comprehensive analysis of features that suggest bipolarity in patients with a major depressive episode: which is the best combination to predict soft bipolarity diagnosis?. J Affect Disord 2013; 147(1–3):150–155CrossRefGoogle ScholarPubMed
Tondo, L.Visioli, C.Preti, A.Baldessarini, R.J.Bipolar disorders following initial depression: modeling predictive clinical factors. J Affect Disord 2014; 167: 44–49CrossRefGoogle ScholarPubMed
Mitchell, P.Parker, G.Jamieson, K.Wilhelm, K.Hickie, I.Brodaty, H.et al.Are there any differences between bipolar and unipolar melancholia? J Affect Disord 1992; 25(2): 97–10510.1016/0165-0327(92)90072-ECrossRefGoogle ScholarPubMed
Olfson, M.Das, A.K.Gameroff, M.J.Pilowsky, D.Feder, A.Gross, R.et al.Bipolar depression in a low-income primary care clinic Am J Psychiatry 2005; 162(11): 2146–2151CrossRefGoogle Scholar
Muzina, D.J.Kemp, D.E.McIntyre, R.S.Differentiating bipolar disorders from major depressive disorders: treatment implications. Ann Clin Psychiatry 2007; 19(4): 305–312CrossRefGoogle ScholarPubMed
Bowden, C.L.A different depression: clinical distinctions between bipolar and unipolar depression. J Affect Disord 2005; 84(2–3):117–12510.1016/S0165-0327(03)00194-0CrossRefGoogle ScholarPubMed
Beesdo, K.Hofler, M.Leibenluft, E.Lieb, R.Bauer, M.Pfennig, A.Mood episodes and mood disorders: patterns of incidence and conversion in the first three decades of life. Bipolar Disord 2009; 11(6): 637–649CrossRefGoogle ScholarPubMed
Geller, B.Zimerman, B.Williams, M.Bolhofner, K.Craney, J.L.Bipolar disorder at prospective follow-up of adults who had prepubertal major depressive disorder. Am J Psychiatry 2001; 158(1): 125–127CrossRefGoogle ScholarPubMed
Hantouche, E.G.Akiskal, H.S.Bipolar II vs. unipolar depression: psychopathologic differentiation by dimensional measures. J Affect Disord 2005; 84(2–3):127–132CrossRefGoogle ScholarPubMed
Paroxetine: a selective serotonin reuptake inhibitor showing better tolerance, but weaker antidepressant effect than clomipramine in a controlled multicenter study. Danish University Antidepressant Group J Affect Disord 1990; 18(4): 289–29910.1016/0165-0327(90)90081-ICrossRefGoogle Scholar
Moclobemide: a reversible MAO-A-inhibitor showing weaker antidepressant effect than clomipramine in a controlled multicenter study. Danish University Antidepressant Group J Affect Disord 1993; 28(2): 105–116CrossRefGoogle Scholar
Clomipramine dose-effect study in patients with depression: clinical end points and pharmacokinetics. Danish University Antidepressant Group (DUAG) Clin Pharmacol Ther 1999; 66(2): 152–165CrossRefGoogle Scholar
Citalopram: clinical effect profile in comparison with clomipramine. A controlled multicenter study. Danish University Antidepressant Group Psychopharmacology 1986; 90(1): 131–138CrossRefGoogle Scholar
Pedersen, C.B.The Danish Civil Registration System. Scand J Public Health 2011; 39(7 Suppl.):22–25CrossRefGoogle ScholarPubMed
Lynge, E.Sandegaard, J.L.Rebolj, M.The Danish National Patient Register. Scand J Public Health 2011; 39(7 Suppl.):30–3310.1177/1403494811401482CrossRefGoogle ScholarPubMed
Carney, M.W.Roth, M.Garside, R.F.The diagnosis of depressive syndromes and the prediction of ECT response. Br J Psychiatry 1965; 111: 659–67410.1192/bjp.111.477.659CrossRefGoogle Scholar
Bech, P.Gram, L.F.Reisby, N.Rafaelsen, O.J.The WHO Depression Scale. Relationship to the Newcastle Scales. Acta Psychiatr Scand 1980; 62(2): 140–153CrossRefGoogle ScholarPubMed
Bech, P.The Bech-Rafaelsen Melancholia Scale (MES) in clinical trials of therapies in depressive disorders: a 20-year review of its use as outcome measure. Acta Psychiatr Scand 2002; 106(4): 252–264CrossRefGoogle ScholarPubMed
Hamilton, M.Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 1967; 6(4): 278–296CrossRefGoogle ScholarPubMed
Bech, P.Clinical psychometrics Oxford: Wiley Blackwell; 2012CrossRefGoogle Scholar
Maier, W.Philipp, M.Comparative analysis of observer depression scales. Acta Psychiatr Scand 1985; 72(3): 239–24510.1111/j.1600-0447.1985.tb02601.xCrossRefGoogle ScholarPubMed
Gibbons, R.D.Clark, D.C.Kupfer, D.J.Exactly what does the Hamilton Depression Rating Scale measure?. J Psychiatr Res 1993; 27(3): 259–273CrossRefGoogle ScholarPubMed
Iwanami, T.Maeshima, H.Baba, H.Satomura, E.Namekawa, Y.Shimano, T.et al.Psychomotor agitation in major depressive disorder is a predictive factor of mood-switching. J Affect Disord 2015; 170: 185–189CrossRefGoogle ScholarPubMed
Maina, G.Salvi, V.Rosso, G.Bogetto, F.Cyclothymic temperament and major depressive disorder: a study on Italian patients. J Affect Disord 2010; 121(3): 199–203CrossRefGoogle Scholar
Bukh, J.D.Andersen, P.K.Kessing, L.V.Rates and predictors of remission, recurrence and conversion to bipolar disorder after the first lifetime episode of depression – a prospective 5-year follow-up study. Psychol Med 2016; 46(6): 1151–1161CrossRefGoogle ScholarPubMed
Akiskal, H.S.Walker, P.Puzantian, V.R.King, D.Rosenthal, T.L.Dranon, M.Bipolar outcome in the course of depressive illness. Phenomenologic, familial, and pharmacologic predictors. J Affect Disord 1983; 5(2): 115–128CrossRefGoogle ScholarPubMed
Gilman, S.E.Dupuy, J.M.Perlis, R.H.Risks for the transition from major depressive disorder to bipolar disorder in the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry 2012; 73(6): 829–836CrossRefGoogle ScholarPubMed
Chun, B.J.Dunner, D.L.A review of antidepressant-induced hypomania in major depression: suggestions for DSM-5. Bipolar Disord 2004; 6(1): 32–42CrossRefGoogle Scholar
Akiskal, H.S.Hantouche, E.G.Allilaire, J.F.Sechter, D.Bourgeois, M.L.Azorin, J.M.et al.Validating antidepressant-associated hypomania (bipolar III): a systematic comparison with spontaneous hypomania (bipolar II). J Affect Disord 2003; 73(1–2):65–74CrossRefGoogle Scholar
Munk-Jorgensen, P.Okkels, N.Golberg, D.Ruggeri, M.Thornicroft, G.Fifty years’ development and future perspectives of psychiatric register research. Acta Psychiatr Scand 2014; 130(2): 87–98CrossRefGoogle ScholarPubMed
Bock, C.Bukh, J.D.Vinberg, M.Gether, U.Kessing, L.V.Validity of the diagnosis of a single depressive episode in a case register. Clin Pract Epidemiol Ment Health 5 2009 4CrossRefGoogle Scholar
Uggerby, P.Ostergaard, S.D.Roge, R.Correll, C.U.Nielsen, J.The validity of the schizophrenia diagnosis in the Danish Psychiatric Central Research Register is good. Dan Med J 2013; 60(2):A4578Google Scholar

References

René Ernst Nielsen, MD, PhD, is head of the research program for Mortality and Morbidity, and co-head of the research program for Affective Disorders at Unit for Psychiatric Research, Aalborg University Hospital, Psychiatry. His main area of research is epidemiology and pharmacoepidemiology in severe mental illness, but he conducts several clinical studies as well.

René Ernst Nielsen is currently supervising several PhD students, and collaborate nationally and internationally on ongoing clinical and epidemiological projects.

He is currently associate editor of Nordic Journal of Psychiatry, and BMC Psychiatry.

Flemming Mørkeberg Nilsson, MD, PhD, is consultant in old age psychiatry at the Municipal Hospital Service in Copenhagen, Denmark. He has been supervisor for two PhD students. He has authored or coauthored 33 peer-reviewed papers. Main research interest is old age psychiatry, with focus on affective disorders in elderly. He has served as course director for education in old age psychiatry in the specialization in psychiatry for 10 years. Newly appointed associate professor in Psychiatry in University of Copenhagen.

Jan B. Valentin: .

I am a biophysicist with a strong background in programming and machine learning including a broad and high-level experience with many different statistical software packages and programming languages, such as C++, Stata, R, Java, Python, and shell scripting. Furthermore, I have experience with parallel programming and speed optimized coding.

I have previously studied chaos and turbulence theory and have also done research on protein folding. In addition, I am skilled within methods such as Markov Chain Mont Carlo, Bayesian networks, survival analysis and a long range of regression-, classification- and clustering techniques.

I am currently employed as a statistician and work with registry as well as clinical studies within the field of psychiatry, from study design to interpretation and dissemination of results.

Kurt Bjerregaard Stage, MD, PhD is consultant in the Department of Psychiatry, Odense University Hospital, Denmark. His research includes issues of affective disorders, psychopharmacology and psychometrics and he is former president of Danish University Antidepressant Group (DUAG).

Per Bech, MD, Dr Sci, FRCPsych (Hon) is professor of Clinical Psychometrics at the University of Copenhagen. His research is especially focusing on the measurement of clinical outcome in schizophrenia, mania, depression, anxiety, side effects of treatment, and subjective well-being.

He is presently the principal or co-supervisor to 6 PhD students. He is member of the editorial boards in several international journals of psychiatry and is author or coauthor of more than 400 papers. He has written and edited books on rating scales.

Per Bech is emeritus editor of European Psychiatry.

MSc pharm and PhD student Tore Bjerregaard Stage is a researcher at University of Southern Denmark. His scientific focus area is focused on research to explain interindividual differences in drug response and statistical methods in health research. He has a total of 16 peer-reviewed publications, one text book (in Danish, ‘Praktisk farmakologi’) and experience as a reviewer of 13 scientific papers.

Kjeld Andersen, MSc, PhD, is professor of Clinical Psychiatry at the University of Southern Denmark, Odense, Denmark. His research is focusing on psychiatric problems in the elderly, including dementia, psychosis and schizophrenia, and alcohol addiction.

He is presently the principal supervisor to 4 PhD students and the lead principal investigator in a multinational study on treatment of alcohol problems in the elderly, a study conducted in Denmark, Germany, and USA. He is the author or coauthor of 40 papers and book chapters.

Rasmus W. Licht, MD, PhD.

Rasmus W. Licht is a chair professor of psychiatry at Aalborg University and a chief psychiatrist at the Aalborg University Hospital and head of the Psychiatric Research Unit. At Aarhus University Hospital, he established the first specialized clinic for bipolar disorders in Denmark. His research is focused on clinical epidemiology of affective disorders, including drug evaluation and trial methodology. He has published several original papers, review articles, editorials and book chapters, and he has contributed to various national and international treatment guidelines on affective disorders. He has served a number of international scientific journals as board member or reviewer.

Jens Holmskov, MD, PhD student.

Jens Holmskov is a resident in psychiatry and a PhD student. He has participated in several scientific studies including studies on treatment of mood disorders conducted by Danish University Antidepressant Group (DUAG). He has also served as reviewer for several international scientific journals.

Submit a response

Comments

No Comments have been published for this article.