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

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.