FDA Approves Once-Daily Lurasidone for Schizophrenia

October 29, 2010 — The US Food and Drug Administration (FDA) has approved the atypical antipsychotic lurasidone (Latuda tablets; Sunovion Pharmaceuticals Inc) for the once-daily treatment of patients with schizophrenia.

Schizophrenia is a chronic, severe, and disabling brain disorder that affects about 2.4 million US adults. It is characterized by positive symptoms (eg, hallucinations, delusions, thought, and movement disorders), negative symptoms (eg, flat affect and lack of social interaction), and cognitive symptoms (such as poor executive functioning, attention span, and working memory).

"Schizophrenia can be a devastating illness requiring lifelong treatment," said Thomas Laughren, MD, director of the Division of Psychiatry Products in the FDA's Center for Drug Evaluation and Research, in an agency news release. "Some patients do not respond well to certain types of drug therapy, so it is important to have multiple treatment options available.

Lurasidone approval was based on data from 4 short-term (6-week) studies of 1287 adults with schizophrenia (mean age, 38.8 years; range, 18 - 72 years). Efficacy was evaluated using the Positive and Negative Syndrome scale (PANSS), a multisymptom inventory of general psychopathology with total scores ranging from 30 to 210; the Brief Psychiatric Rating scale (BPRSd), a multisymptom scale that focuses on positive symptoms of schizophrenia with scores ranging from 18 to 126; and the Clinical Global Impression severity scale (CGI-S), a validated clinician-rated scale that measures current illness on a 1- to 7-point scale.

Results at 6 weeks showed that:

fixed doses of 40 mg/day and 120 mg/day lurasidone yielded significant improvements from baseline relative to placebo on BPRSd total score and CGI-S (mean difference from placebo, −5.6 ± 2.1 and −6.7 ± 2.2; P < .05);
a fixed dose of 80 mg/day lurasidone was significantly more effective than placebo for improving BPRSd (mean difference from placebo, −4.7 ± 1.8; P < .05) and CGI-S scores from baseline;
fixed doses of 40 mg/day and 120 mg/day lurasidone and an active control (olanzapine) yielded significant improvements from baseline relative to placebo on PANSS total score and the CGI-S (mean difference from placebo, −9.7 ± 2.9, −7.5 ± 3.0, and −12.6 ± 2.8, respectively; P < .05 for all); and
of 3 fixed doses of lurasidone (40, 80, or 120 mg/day), only the 80 mg/day dose was significantly more effective than placebo for improving PANSS total score from baseline (mean difference from placebo, −6.4 ± 2.5 [P < .05] vs 40 mg/day dose, −2.1 ± 2.5 and 120 mg/day dose, −3.5 ± 2.5).

The recommended starting dose is 40 mg taken once daily with food; initial dose titration is not required, and the maximum daily dose is 80 mg. The 120-mg dose does not appear to confer added benefit and has been linked to an increased risk for certain adverse events.

Because lurasidone is predominantly metabolized by the hepatic cytochrome P 450 isoenzyme 3A4 (CYP 3A4), concomitant use of strong enzyme inhibitors (eg, ketoconazole) and inducers (eg, rifampin) is contraindicated. Dosing should be limited to 40 mg/day, with coadministration of moderate CYP 3A4 inhibitors such as diltiazem.

Adverse events most commonly reported with lurasidone therapy are those expected with atypical antipsychotics and include somnolence, akathisia, nausea, Parkinsonism, and agitation.

As with other atypical antipsychotic agents, the safety labeling for lurasidone warns of the increased risk for mortality associated with off-label use of the drug to treat behavioral problems in older patients with dementia-related psychosis.

According to a company news release, lurasidone is expected to be available by prescription during the first quarter of 2011.