New Type of Antipsychotic Drug for Schizophrenia Looks Promising
In a 2020 article in the New England Journal of Medicine, researcher Kenneth S. Koblan and colleagues described a new type of antipsychotic drug treatment for schizophrenia. Almost all other antipsychotic drugs block dopamine D2 receptors, while atypical antipsychotics also block the serotonin 5HT2 receptor. They are described as antagonists at these receptors.
In contrast, the new drug is an agonist or activator of two different receptors. The drug SEP-363856 (also called SEP-856) activates the trace amine–associated receptor 1 (TAAR1) and 5-hydroxytryptamine (or serotonin) type 1A (5-HT1A) receptors.
Blocking D2 receptors can cause Parkinson’s-like symptoms (such as tremor, masked faces, and impaired movement or speech) and other extrapyramidal side effects (such as slurred speech, slow movements, or restless legs.) In contrast, SEP-856 seems to have a better side effects profile than these types of drugs while also being highly effective.
Patients with an acute exacerbation of schizophrenia were assigned to receive either placebo or once-daily treatment with SEP-856 (either 50mg or 75mg) for four weeks. A total of 120 patients received SEP-856 while 125 received placebo.
Compared to the placebo group, the SEP-856 group showed significantly greater reductions on a scale of positive and negative symptoms of schizophrenia by the end of the four weeks. Side effects included some sleepiness and gastrointestinal symptoms, but the incidence of extrapyramidal symptoms and changes in the levels of lipids, glycated hemoglobin, and prolactin were similar in both groups. There was one sudden death from cardiac causes in the SEP-856 group, which was not thought to be drug-related.
Editor’s Note: This drug acting on trace amine–associated receptor 1 (TAAR1) and 5HT1A receptors could herald a new and better tolerated type of antipsychotic. It is also being studied for psychosis in Parkinson’s disease. Since all of the antipsychotics that treat schizophrenia have also shown antimanic efficacy, we look forward to future studies of this unique drug in patients with mania.
