Controlled data on optimization of dosing regimen for antipsychotics in schizophrenia is an unmet medical need.

To evaluate the efficacy of low dose lurasidone in schizophrenia; and to determine optimal dosing for patients not achieving improvement in Positive and Negative Syndrome Scale (PANSS) total score by week 2 of standard dosing.

Patients with schizophrenia were randomized to double-blind treatment with fixed daily doses of lurasidone 18.5 mg (for 6 wks; N=101), 74 mg (for 2 wks; N=198), or placebo (for 6 wks; N=112). After 2 weeks of treatment, patients in the 74 mg group with <20% PANSS improvement were re-randomized to continue on the 74 mg dose, or increase to a dose of 148 mg, for the next 4 wks.

Lurasidone 18.5 mg did not demonstrate significant improvement vs. placebo at Week 6 (−17.6 vs −14.5; P=0.25). In the group with <20% PANSS improvement after 2 weeks (N=95), titration to lurasidone 148 mg resulted in significantly greater improvement in PANSS total score at Week 6 compared with 4 additional weeks of treatment at the 74 mg dose (−16.6 vs. −8.9; p=0.023).

This trial supports the 37 mg/d dose of lurasidone as minimally effective dose in patients with acute schizophrenia consistent with evidence from previous studies. Increasing the dose of lurasidone to 148 mg/d after 2 weeks of nonresponse at 74 mg/d resulted in a significant efficacy advantage with important potential implications for clinical practice.

NCT01821378.

Sponsored by Sunovion Pharmaceuticals Inc.