Lurasidone, an atypical antipsychotic, showed efficacy in doses of 40 to 160 mg once daily in patients with acute schizophrenia in 5 short-term, fixed-dose, placebo-controlled trials [Loebel A et al. Schizophr Res. 2013; Nasrallah HA et al. J Psychiatr Res. 2013; Ogasa M et al. Psychopharmacology. 2013; Meltzer HY et al. Am J Psychiatry. 2011; Nakamura M et al. J Clin Psychiatry. 2009]. In short-term studies, early nonresponse to atypical antipsychotics predicted nonresponse [Kinon BJ et al. Neuropsychopharmacology. 2010; Kinon BJ et al. Schizophr Res. 2008], although evidence to support continuation of initial therapy, dose escalation change in medication, and other clinical decisions is lacking.

Antony Loebel, MD, Sunovion Pharmaceuticals, Marlborough, Massachusetts, USA, presented a poster with results from the 6-week, randomized, double-blind, placebo-controlled lurasidone low-dose–high-dose study [NCT01821378]. Lower doses of lurasidone were not evaluated in a placebo-controlled trial in which assay sensitivity was established. Therefore, the objective of this study was to evaluate the efficacy and safety of lurasidone 20 mg per day in adults with an acute exacerbation of schizophrenia (defined by a Positive and Negative Syndrome Scale [PANSS] total score ≥ 80, a PANSS item score ≥ 4 on ≥ 2 PANSS items, and a Clinical Global Impression-Severity [CGI-S] scale score ≥ 4), and to determine an effective treatment strategy for patients who did not have a meaningful reduction in the PANSS total score by week 2 of standard-dose lurasidone (early nonresponders).

After a washout and screening period, patients were randomly assigned 1:2:1 to fixed-dose lurasidone 20 mg per day (n = 1010), 80 mg per day (n = 198), or placebo (n = 112). Patients were well matched for baseline characteristics. Their mean age was 41 years, about a third were women, and 75% were white; the mean PANSS and CGI-S scores were 97 and 4.9.

Patients in the 20-mg group received the same dose throughout the study. After 2 weeks, patients in the 80-mg group classified as early responders (n = 100; ≥ 20% improvement in PANSS total score) continued that dose for the rest of the study; those classified as early nonresponders were randomly assigned 1:1 to continue 80 mg (n = 52) or 160 mg (n = 43) until study end. The mean changes in PANSS total score in the placebo, lurasidone 20-mg, and lurasidone 80- or 160-mg groups, respectively, were −14.5, −17.6, and −24.9 (P < .001 vs placebo).

Adverse events (AEs) associated with lurasidone included akathisia, headache, and nausea; AEs associated with placebo included insomnia and agitation. Serious treatment-emergent AEs were lower with lurasidone at each dose (3.0%) than with placebo (7.1%). No deaths occurred during the study. The incidence of AEs varied across the groups of early responders and nonresponders, but whether the differences were statistically significant was not reported.

Although 20 mg dosing was safe and tolerable, it did not lead to significant improvement; therefore, the minimum effective dose of lurasidone appeared to be 40 mg per day in the present study. Patients with acute schizophrenia whose symptoms do not respond to 80 mg per day of lurasidone after 2 weeks of treatment may benefit from a dose increase to 160 mg per day rather than continuing the initial dose, according to the investigators.