Lurasidone in the long-term treatment of Japanese patients with bipolar I disorder: a 52 week open label study

Abstract

Background: The current study evaluated the long-term (52 week) safety and impact on symptom measures of lurasidone (with or without lithium or valproate) for the treatment of bipolar I disorder in Japanese patients.

Methods: Bipolar patients for this open-label flexibly dosed lurasidone (20-120 mg/day) study were recruited from those with a recent/current depressive episode who completed an initial 6 week, double-blind, placebo-controlled, lurasidone study (depressed group), and those with a recent/current manic, hypomanic, or mixed episode (non-depressed group) who agreed to enroll directly into the long-term study. Measures of adverse events and safety included treatment-emergent adverse events, vital signs, body weight, ECG, laboratory tests, and measures of suicidality and extrapyramidal symptoms. Symptom measures included Montgomery Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS).

Results: The most common adverse events associated with lurasidone were akathisia (30.7%), nasopharyngitis (26.6%), nausea (12.1%), and somnolence (12.1%). Minimal changes in lipids and measures of glycemic control occurred. Mean change in body weight was + 1.0 kg in the non-depressed group and - 0.8 kg in the depressed group. MADRS total scores declined by a mean (SD) of 2.0 (14.7) points from long-term baseline to endpoint in the depressed group who had received placebo in the prior 6 week trial. The depressed group that had received lurasidone during the prior 6 week study maintained their depressive symptom improvements. For the non-depressed group, YMRS total scores decreased over time.

Limitations: No control group was included, treatment was open-label, and 49.7% of patients completed the 52 week study.

Conclusions: Long-term treatment with lurasidone 20-120 mg/day for Japanese patients with bipolar disorder maintained improvements in depressive symptoms for depressed patients who were treated in a prior 6 week trial and led to improvements in manic symptoms among a newly recruited subgroup of patients with a recent/current manic, hypomanic, or mixed episode. Few changes in weight or metabolic parameters were evident.

Clinical trial registration: JapicCTI-132319, clinicaltrials.gov-NCT01986114.

Keywords: Atypical antipsychotic; Bipolar disorder; Lurasidone.

Conflict of interest statement

Teruhiko Higuchi reports personal fees from Meiji Seika Pharma, MSD, Allergan, Eisai, Pfizer, Janssen, Lundbeck, Shionogi, Yoshitomi, Kyowa Hakko Kirin, Mochida, Otsuka, Sumitomo Dainippon, Mitsubishi Tanabe, Eli Lilly, and Takeda. Tadafumi Kato reports personal fees from Kyowa Hakko Kirin, Eli Lilly, Otsuka Pharmaceutical, GlaxoSmithKline, Taisho Toyama Pharmaceutical, Sumitomo Dainippon Pharma, Meiji Seika Pharma Pfizer, Mochida Pharmaceutical, Shionogi, Janssen Pharmaceutical, Janssen Asia Pacific, Yoshitomiyakuhin, Astellas Pharma, Wako Pure Chemical Industries, Wiley Publishing Japan, Nippon Boehringer Ingelheim Kanae Foundation for the Promotion of Medical Science, MSD, Kyowa Pharmaceutical, and Takeda Pharmaceutical, and also reports a research grant from Takeda Pharmaceutical. Mari Miyajima, Kei Watabe, Takahiro Masuda, and Katsuhiko Hagi are full-time employees of Sumitomo Dainippon Pharma Co., Ltd. Jun Ishigooka reports grants from Sumitomo Dainippon during the conduct of the study, personal fees from Meiji Seika Pharma, MSD, Astellas, Novartis, Pfizer, Otsuka, Eli Lilly, Takeda, and Eisai.

© 2021. The Author(s).

Figures

Fig. 1

Study flow diagram and subject disposition during 52 weeks of long-term treatment with lurasidone. Depressed episode group consisted of Japanese patients who had completed an initial 6 week, double-blind, placebo-controlled, evaluation of lurasidone. PBO to LUR = received placebo during prior 6 week trial followed by lurasidone (flexibly dosed 2–120 mg/day) in 52 week long-term trial. LUR to LUR = received lurasidone (flexibly dosed at either 20–60 or 80–120 mg/day) during prior 6 week trial followed by lurasidone (flexibly dosed 20 to 120 mg/day) in 52 week long-term trial. Non-depressed episode group consisted of Japanese patients with bipolar I disorder whose current or most recent episode was a mania, hypomania, or mixed episode. LUR lurasidone, PBO placebo