HOLLYWOOD, FLA. – Lurasidone resulted in significantly less daytime sleepiness and improved cognitive performance, compared with extended-release quetiapine in a long-term, double-blind, head-to-head comparative trial in patients with schizophrenia.
The 6-month, double-blind study involved 207 patients on lurasidone (Latuda) flexibly dosed at 40-160 mg once daily in the evening and 85 patients on extended-release quetiapine (Seroquel XR) at 200-800 mg/day.
One of the two major endpoints was change in daytime alertness as measured by the validated Epworth Sleepiness Scale. From a mean baseline ESS of 5.9, scores in the lurasidone group improved to a mean of 4.4. This was a significantly greater improvement in daytime sleepiness than with quetiapine, where scores went from 6.48 to 5.9, Philip D. Harvey, Ph.D., reported at a meeting of the New Clinical Drug Evaluation Unit sponsored by the National Institute of Mental Health.
The other major endpoint was change over time in cognitive performance as assessed using the computerized CogState schizophrenia battery. From a mean baseline composite Z-score of –3.9, scores in the lurasidone group improved by roughly 1.5 points, a threefold greater gain than in patients on quetiapine, added Dr. Harvey, professor of psychiatry and behavioral sciences, and chief of the division of psychology at the University of Miami.
Although it seems logical that daytime sleepiness would impair cognition and interfere with everyday functional capacity, in a multivariate analysis, the superior cognitive performance at month 6 in the lurasidone group was independent of the antipsychotic agent’s effect upon sleepiness.
Lurasidone has greater affinity for serotonin 5HT7 and 5HT1A receptors than other second-generation antipsychotic agents. These receptors are abundant in areas of the brain involved in sleep, mood regulation, and memory. These pharmacologic attributes provide a biologic basis in support of the improvements in cognitive performance and daytime sleepiness seen in the head-to-head trial.
Dr. Harvey is a consultant to Sunovion Pharmaceuticals, which sponsored the comparative trial, as well as to a half-dozen other pharmaceutical companies.