1. An oral compound, SEP-363856 was shown to significantly reduce the total score of the Positive and Negative Symptom Scale (PANSS) from baseline compare to placebo for patients with an acute exacerbation of schizophrenia.
2. One patient treated with SEP-363856 had sudden cardiac death but had history of coronary artery disease and hypertension.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Current antipsychotic treatments rely on dopamine D2 receptor antagonism for psychosis. However, the therapies are limited in the treatment of negative symptoms and cognitive impairment. SEP-363856 was developed as a new class of psychotropic agents with a non-D2-receptor binding mechanism of action for the treatment of psychosis in schizophrenia. As such, this study evaluated the efficacy and safety of SEP-363856 in patients with an acute exacerbation of schizophrenia. The participants were randomized to receive SEP-363856 or placebo treatment for four weeks. The study determined the patients in the SEP-363856 group had a lower PANSS total score from baseline compared to the placebo group. However, one patient in the treatment group did suffer a serious adverse event of sudden cardiac death.
This randomized, double-blind, trial was limited by the short treatment period, which did not allow for the longitudinal measurement of treatment effects over a six to twelve-month timer period. Another limitation of the study was patients over the age of 40 years were excluded from the trial; therefore, the trial results cannot be generalized to patients older than 40 years. Nonetheless, this study was strengthened by the even number of participants discontinuing treatment in both groups and matched sample size. For physicians, these findings highlighted an alternative therapy to be prescribed to patients suffering from an acute exacerbation of schizophrenia.