Lumateperone, a serotonin, dopamine, and glutamate modulator, demonstrated both efficacy and safety in patients with schizophrenia experiencing an acute exacerbation of psychosis, according to the results of a study published in JAMA Psychiatry. Current antipsychotic therapy, effective primarily for positive symptoms but limited with negative symptoms, may be related to serious adverse effects, including motor impairments, prolactin abnormalities, and cardiometabolic disturbances.

Christophe U. Correll, MD, from the department of psychiatry and molecular medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, and colleagues conducted a randomized clinical trial from November 13, 2014 to July 20, 2015. They enrolled 450 patients (mean age, 42.4±10.2 years; 77.1% male) with schizophrenia and an acute exacerbation of psychosis on a 1:1:1 basis in 3 groups: 60 mg lumateperone tosylate, 40 mg lumateperone tosylate, or placebo once daily for 4 weeks. The primary outcome was mean change in the Positive and Negative Syndrome Scale (PANSS) score from baseline to day 29 vs placebo, and the secondary outcome was Clinical Global Impression-Severity of Illness (CGI-S) score.

The 60-mg lumateperone tosylate dose met both primary (PANSS; least-squares mean difference [LSMD], −4.2; 95% CI, −7.8 to −0.6; effect size [ES], −0.3; nominal P =.02) and secondary (CGI-S; LSMD, −0.3; 95% CI, −0.5 to −0.1; ES, −0.4; nominal P =.003) objectives when compared with placebo. For the 40-mg dose of lumateperone tosylate, the change in the PANSS total score (LSMD, −2.6; 95% CI, −6.2 to 1.1; ES, −0.2; nominal P =.16) was not significant, although the CGI-S score was significant (LSMD, −0.2; 95% CI, −0.5 to 0; ES, −0.3; nominal P =.02). In a responder analysis, the researchers found that there was a 30% or greater improvement in PANSS score for 36.5% of patients receiving the 60-mg dose, 36.3% receiving the 40-mg dose, and 25.5% of the placebo group.

Both the 60-mg and 40-mg dose groups experienced significant improvements in PANSS positive symptoms score (P =.006 and P =.04, respectively), but not negative symptoms score, compared with the placebo group. The higher dose group also experienced significant improvement in general psychopathology and psychosocial function. Treatment-emergent adverse events, mainly somnolence, sedation, or fatigue, occurred in 64.7% of the high dose group, 56.7% of the lower dose group, and 50.3% of the placebo group. Otherwise, both doses were well tolerated, without cardiometabolic or endocrine changes vs placebo.


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Limitations included the inclusion criteria, which may constrain the generalizability of the findings to broader populations, and the 4-week treatment duration, which may not provide evidence of the longer-term safety profile or the effectiveness of maintenance therapy.

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The investigators noted that “the effect sizes for PANSS total (0.30) and CGI-S (0.39) reduction in this study are broadly comparable with standard of care and, especially, newly approved antipsychotic effect sizes for overall reduction in symptoms (PANSS total), including brexpiprazole (0.26), cariprazine (0.34), and lurasidone (0.36).”

Disclosures: Several study authors reported ties to the pharmaceutical industry. Please see the original article for a full list of disclosures.

Reference

Correll CU, Davis RE, Weingart M, et al. Efficacy and safety of lumateperone for treatment of schizophrenia. A randomized clinical trial [published online January 8, 2020]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2019.4379