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.

Mood Stabilizers of First and Second Generation

“…In a one-year study in Japan, including BD patients, the drug was used in the same doses as above, with or without lithium or valproate. It was shown that in previously treated patients with bipolar depression, the drug continued the betterment in depressive symptoms and also improved psychiatric conditions in patients with manic, hypomanic, or mixed episodes [69]. Therefore, it seems that lurasidone may successfully meet the criteria for becoming an SGMS.…”

Application of Antipsychotic Drugs in Mood Disorders

“…Lurasidone (20-80 mg/day) combined with lithium or valproate showed a better prophylactic effect on bipolar I disorder than lurasidone placebo [ 79 ]. In a most recent 52-week study of Japanese patients with bipolar disorder, lurasidone at 20-120 mg/day, with or without lithium or valproate, maintained improvements in depressive symptoms for previously treated bipolar depressed patients and led to improvements in manic symptoms among a newly recruited subgroup of patients with a recent/current manic, hypomanic, or mixed episode [ 80 ].…”

Risk of Drug-induced Movement Disorders with Newer Antipsychotic Agents

“…A DBRCT (n = 211) in major depressive disorder with hypomanic features showed lower rates of parkinsonism (2.8%) and akathisia (3.7%) than similar studies in bipolar depression [ 64 ]. A year-long open label study (n = 199) of lurasidone in maintenance BPD treatment demonstrated akathisia in 30.7% and parkinsonism in 7.5% of treated individuals with 4% of individuals discontinuing treatment for akathisia [ 65 ].…”