Long-term head-to-head studies comparing atypical antipsychotics are important for clinical decision making.

To evaluate long-term treatment of schizophrenia with lurasidone (LUR) vs. quetiapine XR (QXR; Study 234), or risperidone (RIS; Study 237).

To assess efficacy and safety of lurasidone relative to other antipsychotics.

In study 234(efficacy and safety), subjects received 12 months double-blind, flexible-dose lurasidone(40-160 mg/day) or QXR(200-800 mg/day) after completing a 6 week, randomized, double-blind, placebo-controlled trial with LUR or QXR. In Study 237 (safety) clinically stable adult outpatients received 12-months double-blind treatment with flexible-dose LUR 40-120 mg/day or RIS 2-6 mg/day.

Study 234: continued treatment of LUR responders (n=139) reduced relapse risk by 27.2% vs. continued QXR treatment of QXR responders (n=79). Hospitalization risk was 56.7% lower with LUR vs. QXR. More LUR subjects achieved sustained remission vs. QXR (61.9% vs. 46.3%; p=0.043; 12 months, LOCF), and lower all-cause discontinuation (48% vs 61%). Triglycerides were reduced with LUR; total and LDL cholesterol were unchanged or reduced. Median prolactin change was +0.6 for LUR vs. -0.7 ng/mL for QXR. Study 237: clinically significant weight gain was observed with LUR 13%) vs. RIS (19%) with median change in prolactin 0.4 vs. 14.8 ng/mL, respectively. Comparable efficacy was observed for LUR and RIS (change from baseline in PANSS total score:-4.7 vs. -6.5, and CGI-Severity score:-0.4 vs. -0.4, respectively).

The results of these two 12-month trials suggest that lurasidone is safe and well-tolerated with efficacy comparable to quetiapine XR and risperidone for long-term treatment of schizophrenia.