Effect of lurasidone dose on cognition in patients with schizophrenia: Post-hoc analysis of a long-term, double-blind continuation study

We previously reported that treatment with 160 mg/d of lurasidone improved cognitive performance in a manner superior to placebo, quetiapine XR 600 mg/d, and lurasidone 80 mg/d, based on a 6-week randomized trial of patients with an acute exacerbation of schizophrenia. The objective of this post-hoc analysis was to explore the cognitive and functional performance of patients whose final doses of lurasidone were 40/80 mg/d, 120 mg/d, and 160 mg/d compared to quetiapine XR 200-800 mg/d (QXR) during a 6-month, double-blind continuation study that followed a short-term trial. Subjects who received final doses of lurasidone 120 mg/d (n = 77) and 160 mg/d (n = 49) showed significantly greater improvement in overall cognitive performance compared to QXR (n = 85) at week 32 (month 6 of the extension study), while those on last doses of 40/80 mg/d (n = 25) showed a trend towards significance at week 32. Mean changes in neurocognitive composite z-score from pre-treatment baseline were significant for the 3 lurasidone final dose groups at both weeks 19 and 32, with composite change scores of z = 1.53, z = 1.43, and z = 1.34 for the lurasidone 40/80 mg/d, 120 mg/d, and 160 mg/d, respectively, at week 32. In contrast, the composite change score was not statistically significant in the overall quetiapine group (z = 0.46), with none of the individual quetiapine doses showing any significant improvement. Functional capacity scores improved in all treatment groups. Our findings indicate improved cognitive performance in patients treated with each of the flexible doses of lurasidone 40-160 mg/d, compared to quetiapine XR 200-800 mg/d. All doses of lurasidone were superior to all doses of quetiapine for cognitive performance.