Clinical outcome in a randomized 1-year trial of clozapine versus treatment as usual for patients with treatment-resistant illness and a history of mania

Objective: Case series and follow-up studies suggest that clozapine may hav e mood-stabilizing properties in addition to antipsychotic action in patien ts with schizoaffective disorder, bipolar type, and bipolar I disorder, but the generalizability of these findings is limited. This article describes a randomized, open study of clozapine add-on therapy versus treatment as us ual for patients with treatment-resistant illness and a history of mania, M ethod: Thirty-eight patients meeting the DSM-IV criteria for schizoaffectiv e or bipolar disorder that was deemed treatment-resistant were randomly ass igned to clozapine add-on treatment (N=19) or treatment as usual (no clozap ine) (N=19) and followed up for 1 year. Patients received monthly ratings o n the Brief Psychiatric Rating Scale, Clinical Global Impression scale, Bec h-Rafaelsen Mania Scale, Hamilton Depression Rating Scale, Scale for the As sessment of Positive Symptoms, Scale for the Assessment of Negative Symptom s, Abnormal Involuntary Movement Scale, and a 40-item side effect checklist . Differences between treatment groups were assessed according to a pattern -mix random-regression model. An additional analysis compared group differe nces in rating scale scores against relative time in the study. Results: Si gnificant between-group differences were found in scores on all rating scal es except the Hamilton depression scale. Total medication use over 1 year s ignificantly decreased in the clozapine group. No significant differences b etween groups in somatic complaints were noted. The subjects with nonpsycho tic bipolar I disorder who received clozapine showed a degree of improvemen t similar to that of the entire clozapine-treated group. Clozapine dose was significantly higher for the patients with schizoaffective illness than fo r those with bipolar disorder. Conclusions: The results of this study suppo rt clozapine's independent mood-stabilizing property. They demonstrate that clozapine use was associated with significant clinical improvement relativ e to treatment as usual.