Long-Term Effectiveness of Lithium in Bipolar Disorder: A Multicenter Investigation of Patients With Typical and Atypical Features/JCP Abstracts December, 2008

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Long-Term Effectiveness of Lithium in Bipolar Disorder: A Multicenter Investigation of Patients With Typical and Atypical Features

Anne Berghöfer, M.D.; Martin Alda, M.D.; Mazda Adli, M.D.; Christopher Baethge, M.D.; Michael Bauer, M.D., Ph.D.; Tom Bschor, M.D.; Tasha Glenn, Ph.D.; Paul Grof, M.D.; Bruno Müller-Oerlinghausen, M.D.; Janusz Rybakowski, M.D.; Alexandra Suwalska, M.D.; and Andrea Pfennig, M.D., M.Sc.

Objective: Poor response to long-term lithium treatment has been reported to be associated with atypical features of bipolar disorder. The purpose of this study was to investigate the influence of atypical symptoms on the effectiveness and stability of long-term lithium treatment in a prospective, multicenter cohort of bipolar patients in a naturalistic setting.

Method: Patients were initially selected according to International Classification of Diseases, 8th Revision, criteria for bipolar disorder and required long-term treatment. Their diagnoses were reconfirmed according to DSM-IV upon its publication. They were prospectively followed for an approximately 20-year period ending in 2004 in 5 centers participating in the International Group for the Study of Lithium-Treated Patients. Examinations included a comprehensive psychiatric evaluation, an assessment of typical and atypical features on an 8-item scale, and an evaluation of clinical course using the morbidity index. Unbalanced repeated-measures regression models with structured covariance matrices were used to assess the extent to which the morbidity index was influenced by atypical symptoms, duration of treatment, and pretreatment features.

Results: A total of 242 patients were followed for a mean period of 10 years. In 142 patients, the number of typical features was greater than the number of atypical features, whereas in 100 patients the number of atypical features was greater than or equal to the number of typical features. The mean morbidity index remained stable over a period of 20 years in both groups of patients and was not significantly associated with the presence of atypical features, the duration of lithium treatment, the number or frequency of episodes, or latency from the onset of bipolar disorder to the start of lithium treatment.

Conclusion: Our study suggests that long-term response to lithium maintenance treatment is stable both in patients with typical and in patients with atypical features. The predominance of either typical or atypical features did not result in different responses to long-term lithium treatment in this sample of bipolar patients.

(J Clin Psychiatry 2008;69:1860-1868. Online Ahead of Print November 18, 2008.)

Received June 21, 2007; accepted March 20, 2008. From the Institute for Social Medicine, Epidemiology and Health Economics (Dr. Berghöfer), the Department of Psychiatry and Psychotherapy, Campus Charité Mitte (Dr. Adli), and Former Research Group Clinical Psychopharmacology, Department of Psychiatry and Psychotherapy, Campus Benjamin Franklin (Dr. Müller-Oerlinghausen), Charité University Medical Center, Berlin, Germany; the Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada (Dr. Alda); the Department of Psychiatry and Psychotherapy, University of Cologne Medical School, Germany (Dr. Baethge); the Department of Psychiatry and Psychotherapy, Universitätsklinikum Carl Gustav Carus Dresden, Technische Universität Dresden, Germany (Drs. Bauer and Pfennig); the Department of Psychiatry and Psychotherapy, Jewish Hospital Berlin, Germany (Dr. Bschor); ChronoRecord Association, Inc., Fullerton, Calif. (Dr. Glenn); Mood Disorders Center of Ottawa and the Department of Psychiatry, University of Toronto, Canada (Dr. Grof); the Department Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland (Drs. Rybakowski and Suwalska); and the International Group for the Study of Lithium-Treated Patients, www.igsli.org (all authors).

The authors would like to thank Ms. Catherine Aubel and Mr. Matthew Gaskins from Charité University Medical Center for their assistance in preparing the manuscript. Ms. Aubel and Mr. Gaskins report no financial or other relationships relevant to the subject of this article.
Dr. Berghöfer has received honoraria from Janssen, GlaxoSmithKline, and Eli Lilly. Dr. Bauer has received grant/research support from AstraZeneca, Eli Lilly and GlaxoSmithKline; has received honoraria from AstraZeneca and Eli Lilly; and has served on speakers or advisory boards for Eli Lilly, GlaxoSmithKline, Novartis, Servier, and Wyeth. The other authors report no additional financial or other relationships relevant to the subject of this article.
Corresponding author and reprints: Anne Berghöfer, M.D., Institute for Social Medicine, Epidemiology and Health Economics, Charité University Medical Center, 10098 Berlin, Germany (e-mail: anne.berghoefer@charite.de).

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