Olanzapine versus lithium in the acute treatment of bipolar mania: A double-blind, randomized, controlled trial☆
Received 7 December 2006; received in revised form 15 April 2007; accepted 24 April 2007.
Abstract
Background
This multicenter, double-blind, randomized, controlled study conducted in China examined the efficacy and safety of olanzapine versus lithium in the treatment of patients with bipolar manic/mixed episodes.
Methods
Patients with bipolar manic or mixed episode (DSM-IV criteria) and Young Mania Rating Scale (YMRS) score≥20 at screening received olanzapine (5–20 mg/day, n=69) or lithium carbonate (600–1800 mg/day, n=71) for 4 weeks. The primary outcome was mean change from baseline in Clinical Global Impressions-Bipolar Version Overall Severity of Illness (CGI-BP) score. Secondary efficacy measures included YMRS, Brief Psychiatric Rating Scale (BPRS), and Montgomery–Åsberg Depression Rating Scale (MADRS) scores. Safety was also assessed.
Results
A significantly greater mean change was observed in olanzapine versus lithium patients in CGI-BP (Overall Severity) (P=0.009), YMRS (P=0.013), BPRS (P=0.032), and CGI-BP (Severity of Mania) (P=0.012) scores. More olanzapine than lithium patients experienced at least one adverse event possibly related to study drug (P=0.038). More olanzapine patients had a clinically significant weight increase (≥7% of baseline weight) compared to lithium patients (P=0.009). More olanzapine patients completed the study than lithium patients, although this difference was not statistically significant (olz, 91.3%; lith, 78.9%; P=0.057).
Limitations
No placebo arm was included; however both treatments have previously been reported to be more effective than placebo.
Conclusions
These results suggest that olanzapine has superior efficacy to lithium in the acute treatment of patients with bipolar mania over a 4-week period. However, adverse events were experienced by a greater number of olanzapine patients than lithium patients.
gSuzhou Psychiatric Hospital, Suzhou, People's Republic of China
hRenmin Hospital of Wuhan University, Wuhan, People's Republic of China
iNanjing Brain Hospital, Nanjing, People's Republic of China
j2nd Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, People's Republic of China
kInstitute of Mental Health, Peking University, Beijing, People's Republic of China
Corresponding author. Lilly Research Laboratories, Indianapolis, IN 46285, USA. Tel.: +1 317 277 9585; fax: +1 317 276 7845.
☆ Conflict of interest. This study was sponsored by Eli Lilly and Company. M. Tohen, A. Qiuqing, H. McElroy, and E. Pope are employees of Eli Lilly and Company. G. Niufan, Y. Fude, L. Ming, W. Gaohua, Z. Xinbao, L. Huichun, and S. Liang are clinical investigators for the F1D-GH-LOBV study (upon which the manuscript is based), for which their institutions were funded by Eli Lilly and Company for the time spent and assessment cost. The authors have no other potential conflicts of interest to disclose.
Contributors. M. Tohen and A. Qiuqing were involved in the conception and design of the study. H. McElroy undertook the statistical analyses. E. Pope conducted the literature searches, and drafted the manuscript. G. Niufan, Y. Fude, L. Ming, W. Gaohua, Z. Xinbao, L. Huichun, and S. Liang were involved in the acquisition of data. All authors contributed to the interpretation of the data, critical revision of the manuscript for important intellectual content, and have approved the final manuscript.
Role of funding source. Eli Lilly and Company (Lilly) provided funding for this study and was involved in the study conception and design. Lilly had no role in the collection of data for this particular manuscript, beyond the provision of clinical report forms and undertaking clinical monitoring of study sites. Lilly was involved in the analysis and interpretation of data for this manuscript, and in the drafting of the manuscript. Outside of the Lilly employees listed as authors (M. Tohen, A. Qiuqing, H. McElroy, and E. Pope), Lilly had no role in the decision to submit the paper for publication.
ABSTRACT