The Effects of Long-Term Clozapine Add-On Therapy on the Rehospitalization Rate and the Mood Polarity Patterns in Bipolar Disorders

Jae Seung Chang, M.D.; Kyoo-Seob Ha, M.D., Ph.D.; Kyu Young Lee, M.D.; Yong Sik Kim, M.D., Ph.D.; and Yong Min Ahn, M.D., Ph.D.

Objective: We investigated the effect long-term clozapine add-on therapy has on rehospitalization rate and mood polarity patterns in patients with bipolar disorders.

Method: Clinical data from medical records of 51 patients with bipolar disorder (DSM-IV) treated with clozapine add-on for more than 6 months at the Refractory Bipolar Disorders Clinic of Seoul National University Hospital were retrospectively analyzed. Patients had been registered from 1995 to 2004. Rehospitalization rates were compared before and after clozapine add-on. The clinical polarity of episodes resulting in hospitalizations was also compared. Twenty-seven bipolar patients treated with clozapine add-on for more than 3 years were further analyzed for long-term stability.

Results: The number of hospital days per year was reduced in 90.2% of patients after clozapine add-on. Total number and duration of hospitalizations per year decreased, and the effect size of clozapine add-on was substantially large (Wilcoxon z = -5.48, p < .01 for number of hospitalizations/year; Wilcoxon z = -5.32, p < .01 for hospital days/year; r = -0.54 and -0.53, respectively). Significant reductions were found in the number and duration of hospitalizations associated with manic, depressive, and hypomanic episodes. Number and duration of hospitalizations associated with mixed episodes did not show significant changes. The long-term efficacy of clozapine add-on was supported by continuous reduction in hospital days per year in the 27 selected patients.

Conclusion: Long-term clozapine add-on therapy was effective in reducing the number and duration of rehospitalizations of bipolar patients resistant to conventional treatment. A significant reduction was found in rehospitalizations associated with manic, depressive, and hypomanic episodes, whereas mixed episode-associated rehospitalizations did not show significant changes.

(J Clin Psychiatry 2006;67:461-467)

Received July 9, 2005; accepted Sept. 12, 2005. From the Department of Neuropsychiatry and Clinical Research Institute, Seoul National University Hospital, Chongno-Gu, Seoul (Drs. Chang, Lee, Kim, and Ahn); Department of Neuropsychiatry, Seoul National University Bundang Hospital, Bundang-Gu, Seongnam-Si, Gyeonggi-Do (Dr. Ha); Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine, Chongno-Gu, Seoul (Drs. Ha, Kim, and Ahn); and the Institute of Human Behavioral Medicine, Seoul National University Medical Research Center, Chongno-Gu, Seoul (Drs. Lee, Kim, and Ahn), Republic of Korea.

This study was supported by grant number 03-PJ10-PG13-GD01-0002 from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea. This work was not funded by any pharmaceutical company.

Dr. Ahn has previously received grant and research support from Sanofi-Aventis. Dr. Ha has received grant/research support and/or honoraria from Janssen Korea, GlaxoSmithKline, and Eli Lilly. Dr. Kim has previously received grant/research support and/or honoraria from Novartis, Janssen, Eli Lilly, Pfizer, Sanofi-Aventis, Otsuka, AstraZeneca, Organon, and GlaxoSmithKline and has participated in speakers/advisory boards for Janssen, Otsuka, AstraZeneca, Organon, Eli Lilly, and GlaxoSmithKline. Drs. Chang and Lee report no additional financial or other relationships relevant to the subject of this article.

Corresponding author and reprints: Yong Min Ahn, M.D., Ph.D., Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul, 110-744, Republic of Korea (e-mail: aym@snu.ac.kr).