Safety and efficacy of olanzapine monotherapy and olanzapine with a mood stabilizer in 18-week treatment of manic/mixed episodes for Japanese patients with bipolar I disorder

Abstract

Objective:

To assess the safety and efficacy of 18-week olanzapine monotherapy in Japanese patients with bipolar mania, following a 6-week, placebo- and haloperidol-controlled double-blind study (acute study). For those who discontinued the acute study due to lack of efficacy, safety and efficacy was assessed with a combination therapy of olanzapine and a mood stabilizer.

Research design and methods:

In this open-label, multicenter extension study, patients who completed the acute study received olanzapine (5–20 mg/day) as monotherapy, and patients who discontinued the acute study due to lack of efficacy with greater Young Mania Rating Scale (YMRS) total score than the acute study baseline, received olanzapine in combination with one of three mood stabilizers: lithium, carbamazepine, or valproate. Safety was assessed by treatment-emergent adverse events (TEAEs), vital signs, weight, and extrapyramidal symptoms (EPSs). Efficacy measures included YMRS total score, and response and remission rates of manic symptoms.

Main outcome and measures:

There were no deaths or serious adverse events considered potentially related to olanzapine in the monotherapy group (N = 100) or the combination-therapy group (N = 39). TEAEs occurred in 59.0% and 79.5% of patients in the monotherapy and combination-therapy groups, respectively, and their severities were mostly mild or moderate. Regarding the efficacy measures, in the monotherapy group, mean YMRS change from extension study baseline to endpoint was −3.0, and the response and remission rates at endpoint were 97.0% and 93.0%, respectively. In the combination-therapy group, mean YMRS change from extension-study baseline was −19.8; response and remission rates increased from the extension-study baseline (both 0.0%) to 64.1% and 61.5% respectively by endpoint.

Conclusion:

Olanzapine was generally well tolerated during the 18-week extension period in Japanese patients with bipolar mania. Results of both groups were also generally consistent with US and European studies. Monitoring of metabolic parameters is recommended.

Key words::

• Antipsychotics
• Bipolar mania
• Japanese
• Long-term
• Mood stabilizers
• Olanzapine

Transparency

Declaration of funding

This study was funded by Eli Lilly Japan K.K.

Declaration of financial/other relationships

Ma.T. is a former Eli Lilly employee (up to 2008) and his spouse is an Eli Lilly employee; he has received grant/research support from NIMH Atlas Foundation, Johnson and Johnson; he has served as consultant/advisor for Eli Lilly, GlaxoSmithKline, Bristol-Myers Squibb, Forest, Sepracor, Merck, and Lundbeck; and he is a shareholder of Eli Lilly. S.K. has received research/grant support from Astellas, Dainippon-Sumitomo, GlaxoSmithKline, and Ono; he has served as consultant/advisor for Astellas; and he has received honoraria from Eli Lilly Japan, GlaxoSmithKline, Pfizer, Shionogi, and Asahi-kasei. T.H. has no personal financial relationships to disclose relative to this article. H.K. is an employee and a minor stock-holder of Eli Lilly Japan K.K.; he is the Clinical Research Physician for neuroscience products. Mi.T. is an employee and a minor stock-holder of Eli Lilly Japan K.K.; he is the Medical Consultant for neuroscience products. Y.T. is an employee of Eli Lilly Japan K.K.; he is a statistician working on the neuroscience products.

Acknowledgments

The authors acknowledge Hitomi Sano, Megumi Sugiura and Naoko Takamura (Eli Lilly Japan K.K.) and Drs Smita Agarwal, Sreedevi Boggarapu and Megumi Tanaka (Primo Scientific Corporation, Panama, Republic of Panama) for editorial assistance with the manuscript. The authors also thank the investigators and patients who participated in this 18-week extension study.