THE ANTIDEPRESSANT EFFECTS OF RISPERIDONE AND OLANZAPINE IN BIPOLAR DISORDER

Main Article Content

Roger S. McIntyre
Deborah A. Mancini
Janaki Srinivasan
Sonia McCann McCann
Jakub Z. Konarski
Sidney H. Kennedy

Keywords

Bipolar disorder, risperidone, olanzapine, adjunct therapy, cohort study

Abstract

Objective


To describe the antidepressant effectiveness of olanzapine and risperidone and compare their tolerability when employed adjunctively in bipolar I/II disorder.


 


Method


In an observational study, twenty-one ambulatory subjects with DSM-IV defined bipolar I/II disorder, in any phase of the illness, openly received adjunctive risperidone or olanzapine. The primary efficacy


parameters were the Hamilton Depression Rating Scale (HDRS-17) and the Maier and Philips Severity Subscale. Secondary efficacy parameters included the Young Mania Rating Scale (YMRS) along with the Clinical Global Impressions Scale (CGI). Response was defined as a significant change from baseline to endpoint in the total mean HDRS-17 score. The primary tolerability parameters were the Abnormal Involuntary Movement Scale (AIMS) along with changes in weight and body mass index (BMI-kg/m2). Patients were evaluated prospectively with repeated monthly assessments for up to 6 months.


 


Results


Eleven patients openly received risperidone; 10  received olanzapine adjunctive to  either lithium or divalproex. Total mean HDRS-17 scores significantly decreased from baseline to endpoint in both groups


(p=0.001), with the mean HDRS-17 total scores falling from 17(SD=3.2) to 5(SD=1.5) by 6 months in the risperidone-treated  group  and  from  18  (SD=1.9)  to  7  (SD=2.0)  in  the  olanzapine-treated  group. Differences between the risperidone-treated group and the olanzapine-treated group were not significant at  6  months  (p=0.754). The  mean  doses  of  study  medication were  2.88  (SD=1.6) mg/day  for  the risperidone-treated group and 12.69 (SD=2.3) mg/day for the olanzapine-treated group. Both risperidone


and olanzapine were generally well tolerated. No patients developed tardive dyskinesia. Significant


weight gain was experienced by patients in both groups [mean weight gain at endpoint was 5.9 kg in risperidone (p=0.023) and 11.3 kg in olanzapine (p=0.001)]. There was a significant difference in weight gain between the risperidone-treated group and the olanzapine-treated group (p=0.001).


 


Conclusions


These pilot data, from the first prospective comparison study of risperidone and olanzapine in bipolar disorder, suggest that adjunctive administration of either agent may reduce depressive symptom severity. No subjects receiving risperidone or olanzapine developed tardive dyskinesia. Both compounds imparted substantial weight gain with significantly more weight gain accrual with olanzapine. As this was an observational  study,  the  antidepressant  effect  and  tolerability  profile  of  these  compounds  requires


validation via double-blind placebo controlled investigations.

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