Lurasidone in the Long-Term Treatment of Bipolar I Depression: A 28-week Open Label Extension Study

ABSTRACT Background Lurasidone has demonstrated efficacy for short-term treatment of bipolar depression in a diverse ethnic population including Japanese. This study evaluated the long-term safety and effectiveness of open-label lurasidone treatment in these patients. Methods Patients for this 28-week extension study were recruited from those who completed a 6-week double-blind study of lurasidone, 20-60 mg/day, lurasidone 80-120 mg/day, and placebo. In the extension study, lurasidone was flexibly dosed (20 to 120 mg/day). Safety was evaluated in terms of change from extension-phase baseline to endpoint including adverse events, vital signs, body weight, ECG, laboratory tests, and measures of suicidality and extrapyramidal symptoms. Effectiveness was determined by Montgomery Asberg Depression Rating Scale (MADRS) and other measures. Results 303 of 413 (73.3%) subjects completed the extension study. Discontinuation due to a treatment-emergent adverse event occurred for 11.4% of those who received placebo, and 8.9% of those who received lurasidone, in the prior 6-week trial. The most common treatment-emergent adverse event was akathisia. Minimal changes were evident on body weight and metabolic parameters. Long-term treatment with lurasidone further reduced mean MADRS total scores from long-term baseline to week 28 (or endpoint) for both those who had received prior placebo (-11.3), and those who had receive prior lurasidone (-8.9), in the 6-week double-blind trial. Limitations There was no placebo control and treatment was not double-blind. Conclusions Long-term treatment with lurasidone (20-120 mg/day) was well-tolerated with no new safety concerns and associated with continued improvement in depressive symptoms in this international sample of patients with bipolar depression. Clinical trial registration JapicCTI-132319, clinicaltrials.gov - NCT01986114