Clozapine is widely regarded as the most effective antipsychotic. Yet, if I recall correctly, it is the weakest dopamine D2-blocker among all the antipsychotic medications. Therefore, I’m hopeful that there will eventually be new drugs that are effective without (significant) dopamine antagonism.
SEP-363856 was more effective compared to placebo after 4 weeks of treatment (effect size 0.45). This is encouraging, although the duration of the RCT and relatively selected group of patients preclude firm conclusions on its efficacy. We may be hopeful that antipsychotics with a novel mechanism of action are investigated, but only the future will learn whether SEP-363856 will have true added value to improve the life of patients suffering from psychotic disorders.