Research report
Olanzapine versus lithium in the acute treatment of bipolar mania: A double-blind, randomized, controlled trial

https://doi.org/10.1016/j.jad.2007.04.020Get rights and content

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.

Introduction

Treatment guidelines, while often varied, commonly emphasize the use of lithium, valproate (divalproex), and atypical antipsychotics in the treatment of bipolar mania (Fountoulakis et al., 2005).

Olanzapine is an atypical antipsychotic with proven efficacy in the treatment of bipolar mania in the acute and maintenance settings (Tohen et al., 1999, Tohen et al., 2000, Tohen et al., 2006). To our knowledge, only one study has directly compared olanzapine and lithium in the acute treatment of bipolar mania (Berk et al., 1999). Unfortunately, the small sample size (n = 30) limited the interpretation of the study results. Olanzapine and lithium have also been compared as maintenance therapy in bipolar disorder patients that were acutely stabilized with concomitant olanzapine and lithium therapy (Tohen et al., 2005).

In the present study, conducted in China, the efficacy and safety of olanzapine were compared to lithium in the treatment of patients with bipolar disorder, manic or mixed episodes, with or without psychotic features, as measured by mean change on the CGI Bipolar Version — Overall Severity of Illness scale (CGI-BP; Spearing et al., 1997) over a 4-week period. Secondary objectives included a further comparison of the efficacy of olanzapine and lithium, utilizing the Young Mania Rating Scale (YMRS; Young et al., 1978), Brief Psychiatric Rating Scale (BPRS; Overall and Gorham, 1988), and the Montgomery–Åsberg Depression Rating Scale (MADRS; Montgomery and Åsberg, 1979).

Section snippets

Patients

Inpatients and outpatients aged ≥ 18 years were recruited at seven sites in China. Patients met the DSM-IV criteria (APA, 1994) for an index manic or mixed episode of bipolar disorder (with or without psychotic features), based on a clinical assessment. Patients were required to have a YMRS total score  20 at screening (Visit 1), and prior to the start of active treatment (Visit 2).

This study was reviewed and approved by the institutional review board at each site, and was conducted in accordance

Patient characteristics

Of the 155 patients who entered screening, 140 patients were enrolled and participated in this study between December 2003 and June 2005. Table 1 summarizes the demographic and clinical characteristics, and baseline disease severity of these patients. All patients were diagnosed as experiencing a manic episode at baseline. On average, patients were moderately to markedly ill at baseline, as measured by the mean (± SD) CGI-BP (Overall Severity), YMRS, BPRS, and CGI-BP (Severity of Mania) scores

Discussion

To our knowledge, this is the first double-blind, randomized, controlled trial comparing an atypical antipsychotic versus lithium in the treatment of acute bipolar mania in a study with a large enough sample size to detect a significant difference between the two treatments. The results from this study suggest that olanzapine is more effective than lithium in improving symptoms of bipolar mania, as indicated by significantly greater mean changes from baseline to 4 weeks in CGI-BP (Overall

Acknowledgements

This study (F1D-GH-LOBV) was sponsored by Eli Lilly and Company. Results from this study are presented in part on the clinical trial registry located at www.lillytrials.com, and have been presented in part at the Chinese Psychiatric Association 2006 Academic Congress.

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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.

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