Novel antipsychotics specificity profile: A clinically oriented review of lurasidone, brexpiprazole, cariprazine and lumateperone

Second generation antipsychotics (SGAs) are effective options in the treatment of schizophrenia and mood disorders, each with characteristic efficacy and safety features. In order to optimize the balance between efficacy and side effects, it is of upmost importance to match compound specificity against patient clinical profile. As the number of SGAs increased, this review can assist physicians in the prescription of three novel SGAs already on the market, namely lurasidone, brexpiprazole, cariprazine, and lumateperone, which is in the approval phase for schizophrenia treatment at the FDA. Besides schizophrenia, EMA and/or FDA approved lurasidone for bipolar depression, brexpiprazole as augmentation in major depressive disorder and cariprazine for the acute treatment of manic or mixed episodes associated with bipolar I disorder. These new antipsychotics were developed with the aim of improving efficacy on negative and depressive symptoms and reducing metabolic and cardiovascular side effects compared to prior SGAs, while keeping the risk of extrapyramidal symptoms low. They succeeded quite well in containing these side effects, despite weight gain during acute treatment remains a possible concern for brexpiprazole, while cariprazine and lurasidone show higher risk of akathisia compared to placebo and other SGAs such as olanzapine. The available studies support the expected benefits on negative symptoms, cognitive dysfunction and depressive symptoms, while the overall effect on acute psychotic symptoms may be similar to other SGAs such as quetiapine, aripiprazole and ziprasidone. The discussed new antipsychotics represent useful therapeutic options but their efficacy and side effect profiles should be considered to personalize prescription.