Somnolence and Sedation with Lumateperone Treatment: A Comparison of Morning and Evening Administration

Background: Somnolence and sedation are common treatment-emergent adverse events (TEAEs) reported with current antipsychotics. Lumateperone (lumateperone tosylate, ITI-007), a mechanistically novel antipsychotic that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, is FDA-approved for the treatment of schizophrenia. This analysis evaluated the effects of morning vs evening administration of lumateperone on TEAEs of somnolence and sedation.

Methods: Data were pooled from 3 acute (4 or 6 week) placebo-controlled studies evaluating lumateperone 42mg administered in the morning in patients with an acute exacerbation of schizophrenia; 2 studies included a risperidone 4mg arm. Data from the open-label 1-year trial evaluated patients switched from prior antipsychotic treatment to lumateperone 42mg administered in the evening. Assessments included rates and severity of somnolence/sedation TEAEs and time to resolution (TTR).

Results: Somnolence/sedation was reported less frequently with evening administration of lumateperone 42mg (5.8%) than with morning administration (24.1%). In short-term trials, risperidone had similar rates of somnolence/sedation (23.9%) as lumateperone. Rates of somnolence/sedation (10.0%) were lower with placebo. The majority of somnolence/sedation TEAEs were of mild severity in short-term and long-term studies. Median TTR of somnolence/sedation with lumateperone treatment was similar in the long-term study (25.5 d) and short-term studies (28.0 d). In short-term trials, risperidone and placebo had similar TTR of somnolence/sedation as lumateperone (risperidone: 28.0 d; placebo: 27.5 d).

Conclusion: Though limited by differences in study design, this post hoc analysis of acute and long-term studies suggests that sedation and somnolence events with lumateperone 42mg are transient, usually mild, and less frequent with evening administration.