Lurasidone Dose Escalation in Early Nonresponding Patients With Schizophrenia: A Randomized, Placebo-Controlled Study.

OBJECTIVE

To assess the effect of dose increase in adult patients with schizophrenia who demonstrate inadequate initial response to standard-dose lurasidone and to evaluate the efficacy of low-dose lurasidone in adult patients with schizophrenia.

METHODS

In this randomized, double-blind, placebo-controlled study conducted between May 2013 and June 2014, hospitalized patients with acute schizophrenia (DSM-IV-TR criteria) were randomly assigned to double-blind treatment with lurasidone 20 mg/d (n = 101), lurasidone 80 mg/d (n = 199), or placebo (n = 112). Nonresponders to lurasidone 80 mg/d (Positive and Negative Syndrome Scale [PANSS] score decrease < 20%) at 2 weeks were re-randomized to lurasidone 80 mg/d or 160 mg/d for the remaining 4 weeks of the study. The primary outcome measure was change from baseline to week 6 in PANSS total score.

RESULTS

In nonresponders to lurasidone 80 mg/d (n = 95), dose increase to 160 mg/d at week 2 significantly reduced PANSS total score at week 6 study endpoint compared with continuing 80 mg/d (-16.6 vs -8.9; P < .05 [effect size = 0.52]). While a comparable magnitude of improvement was observed in Clinical Global Impression-Severity (CGI-S) score from week 2 to week 6 endpoint for lurasidone 160 mg/d versus 80 mg/d (-1.0 vs -0.6; effect size = 0.44), the difference was not statistically significant (P = .052). Patients receiving lurasidone 20 mg/d did not demonstrate significant improvement compared with placebo at week 6 in PANSS total (-17.6 vs -14.5; P = .26) or CGI-S (-0.93 vs -0.73; P = .17) scores. Few dose-related adverse effects associated with lurasidone were observed.

CONCLUSIONS

In adult patients with schizophrenia demonstrating nonresponse to 2 weeks of treatment with lurasidone 80 mg/d, dose increase to 160 mg/d resulted in significant symptom improvement compared with continuing lurasidone 80 mg/d. Lurasidone 20 mg/d was not associated with significant improvement in psychotic symptoms in adult patients with schizophrenia.

TRIAL REGISTRATION

ClinicalTrials.gov identifier: NCT01821378.