A Naturalistic Comparison of Clozapine, Risperidone, and Olanzapine in the Treatment of Bipolar Disorder

Background: Our purpose was to evaluate theoverall efficacy and tolerability of novel antipsychoticmedications for patients with bipolar disorder type I.

Method: A retrospective study of theMassachusetts General Hospital Bipolar Clinic database wascarried out to identify 50 consecutive treatment trials inpatients with DSM-IV bipolar disorder type I who had receivedadjunctive treatment with risperidone, olanzapine, or clozapine,along with standard mood stabilizers. The treatment charts ofthose patients (N = 42) were reviewed for details of adverseeffects, tolerability, and efficacy of medication.

Results: Overall results indicated equivalentefficacy in novel antipsychotic treatments according to change inClinical Global Impressions scale score. Levels of extrapyramidalsymptoms were similar in all groups and occurred in 12/42patients (28.6%). Prolactin-related side effects were notobserved in any patients. There were no cases of affective switchor worsening of mania. Substantial weight gain of more than 10 lb(4.5 kg) was significantly greater in patients treated witholanzapine.

Conclusion: These results suggest that theefficacy and tolerability of risperidone, olanzapine, andclozapine are similar in patients with bipolar disorder. Onemajor differentiation factor of these drugs appears to be weightgain, particularly between olanzapine and risperidone. This may,in part, also be related to the need to use mood-stabilizingagents, like lithium or divalproex sodium, which may potentiatethe weight-gain effect of novel antipsychotics.