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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:jho@rn.dk (J. Holmskov).
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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

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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.

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