SAN ANTONIO, TX—Up to 20 weeks of treatment with lurasidone adjunctive to lithium or valproate in patients with bipolar I disorder resulted in a “clinically significant mean improvement in depression and mania scores” during the open-label stabilization phase of a randomized study, according to results presented at the U.S. Psychiatric & Mental Health Congress.

“Response and remission rates were high,” Andrei Pikalov, MD, PhD, of Sunovion Pharmaceuticals Inc., Fort Lee, NJ, and colleagues stated and, among completers, “remission was reported by two-thirds of patients with an index episode of mania/hypomania/mixed mania.”

The study enrolled 962 patients with 1 or more manic, mixed manic, or depressed episodes in the previous 2 years with a Young Mania Rating Scale (YMRS) or Montgomery-Åsberg Depression Rating Scale (MADRS) score of ≥14 if on lithium or valproate or ≥18 if not on either agent to 12–20 weeks of open-label stabilization treatment with lurasidone 20–80mg daily as adjunctive treatment.

Patients were subsequently randomly assigned to 28 weeks of double-blind, placebo-controlled adjunctive lurasidone; however, this study only reported on the effectiveness of adjunctive lurasidone during the stabilization phase.

At baseline, mean age was 42.6 years, 41.0% were male, 81.1% were white, and 57.3% had a lifetime number of bipolar episodes of ≥10%.

Of those enrolled, 756 (78%) non-rapid cycling patients were included in the efficacy analysis, 53.4% with depression and 46.6% with mania/hypomania/mixed-mania. Among those with depression, mean MADRS score was 25.4 and among those with mania/hypomania/mixed mania, mean YMRS score was 19.1.

The most frequent modal daily dose of lurasidone during the open-label phase was 40mg (44.8%), followed by 60mg (29.3%) and 80mg (22.1%).

Among patients with an index episode of depression, lurasidone treatment was associated with a mean last observation carried forward (LOCF)-end point change in MADRS total score of -14.8. Responder rates, defined as a ≥50% reduction in MADRS, were 70.7% for LOCF and 85.4% (observed case).

Those with mania/hypomania/mixed mania had a mean LOCF-end point change in YMRS of -13.6, with responder rates of 82.3% for LOCF and 97.3% for observed case.

At Week 20, the effect of lurasidone on the Clinical Global Impression Bipolar Severity (CGI-BP-S) depression score among patients with an index episode of depression was a reduction in score from a mean of 4.2 at baseline to 1.8; Sheehan Disability Scale (SDS) total score was reduced from a mean of 18.1 to 7.4. The Quality of Life, Enjoyment, and Satisfaction Questionnaire (Q-LES-Q) score increased from a mean of 38.1 to 61.4.

Among patients with an index episode of mania/hypomania/mixed mania, CGI-BP-S depression score was reduced from a mean of 3.7 at baseline to 1.4, while the Sheehan Disability Scale (SDS) total score was reduced from a mean of 13.7 to 4.4. The Q-LES-Q score increased from a mean of 54.8 to 66.7.

The most common adverse events were nausea (11.5%), headache (9.1%), akathisia (8.3%), insomnia (8.0%), somnolence (7.2%), vomiting (6.1%), and diarrhea (5.5). A total of 5.6% of patients discontinued due to an adverse event.

Study limitations “include the open-label, uncontrolled study design, and use of a lower dose range that is not consistent with current dosing recommendations,” they concluded.