Patients with an acute exacerbation of schizophrenia who received an investigational antipsychotic drug daily for 4 weeks had significantly greater improvement in the Positive and Negative Symptom Scale (PANSS) total score, compared with those who received placebo, according to a study in The New England Journal of Medicine.
The drug, SEP-363856, is a novel trace amine-associated receptor 1 (TAAR1) agonist with serotonin 1A (5-HT1A) agonist activity, according to drug developer Sunovion. SEP-363856 does not bind to dopamine 2 (D2) or serotonin 2A (5-HT2A) receptors.
“For the last 60 years, antipsychotics that bind to dopamine receptors have been the standard of care, despite their side effect profile. It is my hope that these results for SEP-363856 support a new schizophrenia treatment for people who have been diagnosed with this serious mental health condition,” said study coauthor John Krystal, MD, psychiatry chair and codirector of the Yale Center for Clinical Investigation at Yale School of Medicine, New Haven, Connecticut.
“SEP-363856 could have a big impact on people with schizophrenia, their families, and on the public health burden posed by schizophrenia.”
The 4-week trial included 245 adults with an acute exacerbation of schizophrenia; 120 patients were randomized to receive daily SEP-363856 (50 mg or 75 mg), and 125 patients received placebo.
The average drop in PANSS total score was 17.2 points in patients who received SEP-363856, compared with 9.7 points in patients who received placebo, according to the study. Patients who received the investigational drug also showed improvement in overall severity of illness, as measured by the Clinical Global Impressions-Severity scale.
Adverse events with SEP-363856 included somnolence and gastrointestinal symptoms. In addition, one sudden cardiac death occurred in the SEP-363856 group, researchers reported. Extrapyramidal symptoms and changes in lipid, glycated hemoglobin, and prolactin levels were similar in both groups.
“Longer and larger trials are necessary to confirm the effects and side effects of SEP-363856,” researchers concluded, “as well as its efficacy relative to existing drug treatments for patients with schizophrenia.”