2012 APA - IPS: Two Studies Confirm Efficacy of Lurasidone for Bipolar 1 Depression

Posters present results of clinical trials that examined lurasidone as monotherapy and as part of combination therapy in patients with bipolar 1 depression with or without rapid cycling and without psychotic features.

New York, NY — Dual studies examining the efficacy of lurasidone for patients with bipolar 1 depression with or without rapid cycling and without psychotic features were presented in side-by-side poster sessions at the American Psychiatric Association 64th Institute on Psychiatric Services.

One of the studies evaluated the efficacy and safety of lurasidone as monotherapy for this patient population. Patients were randomized to six weeks of once-daily double-blinded treatment with either lurasidone 20-60 mg/d (N=123, mean modal dose 34.9 mg/d), lurasidone 80-120 mg/d (N=124, mean modal dose 92.3 mg/d) or placebo (N=127).

The primary endpoint of the study was the Montgomery-Asberg Depression Rating Scale, (MADRS), a 10-point questionnaire used to diagnose depression severity. In both dosage groups, use of lurasidone showed statistically significant reduction of MADRS scores from baseline compared to placebo (-15.4, P<0.001). “We saw statistically significant separation from placebo on the MADRS score beginning at week 2 and through week 6 with lurasdione monotherapy,” said Hans Kroger, PhD, one of the study authors.

In a companion study, lurasidone was evaluated in patients with bipolar 1 depression as adjunctive therapy to lithium or valproate. The selection of these agents was desirable to mimic a real-world environment. Patients who were failing on a regimen of lithium or valproate were randomized to adjunctive therapy for 6 weeks of double-blinded treatment with lurasidone 20-120 mg/d (N= 143) or placebo (N=136).

At the 6-week endpoint, the adjunctive use of lurasidone with either lithium or valproate showed significant reduction in MADRS scores from baseline compared to placebo (-17.1 vs -13.5, P<0.001). “In this study we also saw statistical separation from placebo on the MADRS, as early as 3 weeks and at 6 weeks,” Kroger said.

From a clinical perspective, changes from baseline in the Clinical Global Impression Scale for rating manic and depressive episodes saw similar separation from placebo as early as 2 weeks in both studies. Improvements were also documented in patient quality of life and ability to function as reported by the Quick Index of Depressive Symptomatology Index-Self Report and the Sheehan Disability Scale, as well as improvements in anxiety as assessed by the Hamilton Anxiety Rating Scale.

Lurasidone received approval for the treatment of schizophrenia in 2010. Two applications for the use of lurasidone as monotherapy and as adjunctive therapy for adults with depressive episodes associated with bipolar 1 disorder were submitted to the FDA in August of this year.

Study completion rates were approximately 74% in all three groups. The most frequently reported adverse events for lorasidone were nausea, headache, and insomnia. Major depressive episodes in patients with bipolar 1 depression have been reported to cause severe functional impairment in 90% of individuals.

The abstract of this study is available here.