Fran Lowry

June 23, 2014

HOLLYWOOD, Florida — In adults with bipolar I depression who have had an insufficient response to monotherapy, adding lurasidone (Latuda, Sunovion Pharmaceuticals Inc) to lithium or valproate (Depakote, AbbVie Inc) improves depressive symptoms.

"For the first time, we now have a compound that has been shown to be efficacious both as monotherapy and when used adjunctively with lithium and valproate," lead author Joseph R. Calabrese, MD, professor of psychiatry, Case Western Reserve School of Medicine, Cleveland, Ohio, told Medscape Medical News. "Such a study has never once been successfully conducted before."

Few studies have been reported that demonstrate the efficacy of adjunctive therapy for patients with bipolar I depression who have not had a complete response to monotherapy with mood stabilizing agents, Dr. Calabrese said.

"When a subject is enrolled in an adjunctive design trial, they have already had a partial response to lithium or valproate. That makes it much harder for the new treatment to win, to show efficacy, and the likelihood of success goes way down. So these adjunctive studies are much more important than monotherapy studies because they tell us what the true effect size is in the real world," he said.

The pooled results of the 2 6-week efficacy and safety studies of lurasidone plus lithium or valproate in bipolar I depression were presented here at the American Society of Clinical Psychopharmacology (ASCP) 2014 Annual Meeting.

Dr. Joseph Calabrese

Patients received double-blind treatment with lurasidone 20 to 120 mg per day (n = 355 patients) or placebo (n = 327 patients), together with lithium or valproate. Primary efficacy measures were the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impression Bipolar Severity of Illness (CGI-BP-S) scale.

Secondary efficacy outcomes included the Quick Inventory of Depressive Symptomology–Self Report (QIDS-SR-16), the Hamilton Anxiety Rating Scale (HAM-A), and Quality of Life, Enjoyment and Satisfaction Questionnaire (Q-LES-Q).

Compared with placebo, 6 weeks of treatment with lurasidone was associated with improvement in the mean MADRS score (-14.4 with lurasidone vs -11.9 with placebo; P = .003), as well as improvement in the CGI-BP-S score (-1.7 vs -1.3; P = 0.001).

Similarly, improvement was seen in all secondary efficacy measures.

Table. Secondary Efficacy Results

Measure Lurasidone Placebo P-Value
QIDS-SR-16 -7.4 5.7 <0.001
HAM-A -7.0 -5.0 <0.001
Q-LES-Q +18.5 +13.2 <0.001

 

Rates of response, defined as a reduction of 50% or more in the MADRS, were significantly higher with lurasidone compared with placebo (48% vs 37%; P = .002).

Discontinuation rates were similar for lurasidone and placebo, with 5.8% of lurasidone patients and 4.8% of placebo patients dropping out because of adverse events. Adverse events that occurred with at least a 5% incidence were nausea, Parkinsonism, somnolence, and akathisia. All of these were more frequent in the lurasidone group compared with placebo.

Additionally, lurasidone had minimal effects on weight or metabolic parameters.

Growing Evidence Base

"This report follows publication of a large clinical trial earlier this year in the American Journal of Psychiatry in which adjunctive lurasidone added to ongoing clinically determined treatment with lithium or valproate in adults with bipolar I depression despite at least 4 weeks' treatment with therapeutic levels of lithium or valproate was well tolerated and associated with moderate reduction in depressive and anxiety symptoms," Anne Eden Evins, MD, MPH, director of the Center for Addiction Medicine at Massachusetts General Hospital, Boston, told Medscape Medical News.

"This is highly significant, as few agents have been shown to improve symptoms over and above the therapeutic action of lithium or valproate, and residual depressive symptoms despite mood stabilizer treatment is a major clinical problem for people with bipolar I disorder, interfering greatly with quality of life," Dr. Evins, who was not part of the study, said.

The study was funded by Sunovion Pharmaceuticals Inc. Dr. Calabrese reports financial relationships with AstraZeneca, Benecke, Biomedical Development Corp, Cephalon, Convergent Health Solutions, Cortex Congress, Eisai, Elan, Forest Labs, GSK, Health & Wellness, Hoffman LaRoche, Lundbeck, Medwiz Healthcare, Merck, Otsuka, Pfizer, Promedica Scientia, Spirant Communications Private Limitrex, Sunovion Pharmaceuticals Inc, Takeda, and Teva. Dr. Evins reported no relevant financial relationships.

American Society of Clinical Psychopharmacology (ASCP) 2014 Annual Meeting. Abstract 13. Presented June 16, 2014.

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