It is approved for the treatment of schizophrenia as well as bipolar depression, as either monotherapy or adjunctive therapy (with lithium or valproate).

[3] Lumateperone was approved for medical use in the United States in December 2019 with an initial indication for schizophrenia,[4][5] and became available in February 2020.

On December 20, 2019, the United States Food and Drug Administration (FDA) approved lumateperone for the treatment of schizophrenia in adults.

[4][5][6] In December 2021, the FDA approved lumateperone for the treatment of bipolar depression in adults as monotherapy and as adjunctive therapy with lithium or valproate.

[8] Lumateperone is associated with a low rate of serum aminotransferase elevations during therapy, but has not been linked to instances of clinically apparent acute liver injury.

It has additional off-target antagonism at α1 receptors, without appreciable antimuscarinic or antihistaminergic properties, limiting side effects associated with other atypical antipsychotics.

Study 404 patients saw an improvement of depressive symptoms compared to placebo as documented by a change in MADRS total score of 4.6.