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Stability of lithium treatment in bipolar disorder - long-term follow-up of 346 patients

Anne Berghöfer1*, Martin Alda2, Mazda Adli3, Christopher Baethge4, Michael Bauer5, Tom Bschor6, Paul Grof7, Bruno Müller-Oerlinghausen8, Janusz K Rybakowski9, Alexandra Suwalska9 and Andrea Pfennig5

Author Affiliations

1 Institute for Social Medicine, Epidemiology and Health Economics, Charité University Medical Center, Berlin 10098, Germany

2 Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia B3H 4R2, Canada

3 Department of Psychiatry and Psychotherapy, Charité University Medical Center, Berlin 10098, Germany

4 Department of Psychiatry and Psychotherapy, University of Cologne Medical School, Cologne 50923, Germany

5 Department of Psychiatry and Psychotherapy, Universitätsklinikum Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden 01307, Germany

6 Department of Psychiatry, Schlosspark Clinic, Berlin 14059, Germany

7 Mood Disorders Center of Ottawa and Department of Psychiatry, University of Toronto, Toronto M5S 2E4, Canada

8 Drug Commission of the German Medical Association, Berlin 10623, Germany

9 Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan 61-701, Poland

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International Journal of Bipolar Disorders 2013, 1:11  doi:10.1186/2194-7511-1-11

Published: 31 July 2013



The purpose of this study was to investigate the effectiveness and stability of long-term lithium treatment in a prospective, international, multicenter cohort of bipolar patients in a naturalistic setting.


Patients were selected according to DSM IV criteria for bipolar disorder and required long-term treatment. They were prospectively followed and documented in five centers belonging to the International Group for the Study of Lithium-Treated Patients. This was a prospective cohort study without a comparison group. Lithium treatment was administered in a naturalistic and specialized outpatient setting. All patients underwent a comprehensive psychiatric examination, which included the use of standard rating scales, as well as an evaluation of clinical course based on the morbidity index (MI).

Wald tests were used to assess the significance of fixed effects and covariates when analyzing the relationship between depressive, manic, and total morbidity index and several characteristics of illness course.

Results and discussion

A total of 346 patients with bipolar disorder I or II were followed for a mean period of 10.0 years (standard deviation (SD) 6.2, range 1 to 20). The morbidity index remained stable over time: the mean MI was 0.125 (SD 0.299) in year 1 and 0.110 (SD 0.267) in year 20. The MI was not associated with the duration of lithium treatment, the number or frequency of episodes prior to treatment, or latency from the onset of bipolar disorder to the start of lithium treatment. The drop-out rate was high over the study period. Our findings suggest that long-term response to lithium maintenance treatment remains stable over time.

Bipolar disorder; Lithium; Long-term treatment; Morbidity index; Stability