A Naturalistic Comparison of Clozapine, Risperidone, and Olanzapine in the Treatment of Bipolar Disorder
J Clin Psychiatry 2000;61(9):638-642
© Copyright 2017 Physicians Postgraduate Press, Inc.
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Background: Our purpose was to evaluate the
overall efficacy and tolerability of novel antipsychotic
medications for patients with bipolar disorder type I.
Method: A retrospective study of the
Massachusetts General Hospital Bipolar Clinic database was
carried out to identify 50 consecutive treatment trials in
patients with DSM-IV bipolar disorder type I who had received
adjunctive treatment with risperidone, olanzapine, or clozapine,
along with standard mood stabilizers. The treatment charts of
those patients (N = 42) were reviewed for details of adverse
effects, tolerability, and efficacy of medication.
Results: Overall results indicated equivalent
efficacy in novel antipsychotic treatments according to change in
Clinical Global Impressions scale score. Levels of extrapyramidal
symptoms were similar in all groups and occurred in 12/42
patients (28.6%). Prolactin-related side effects were not
observed in any patients. There were no cases of affective switch
or worsening of mania. Substantial weight gain of more than 10 lb
(4.5 kg) was significantly greater in patients treated with
Conclusion: These results suggest that the
efficacy and tolerability of risperidone, olanzapine, and
clozapine are similar in patients with bipolar disorder. One
major differentiation factor of these drugs appears to be weight
gain, particularly between olanzapine and risperidone. This may,
in part, also be related to the need to use mood-stabilizing
agents, like lithium or divalproex sodium, which may potentiate
the weight-gain effect of novel antipsychotics.