Evaluating lumateperone for its use in treating depressive episodes associated with bipolar I or II disorder in...

Lumateperone is a novel antipsychotic medication that has recently received approval by the United States Food and Drug Administration for treatment of major depressive episodes of type I and II bipolar disorder. It is approved for use as monotherapy or as an adjunctive treatment to lithium or valproic acid.

Clinical trials performed with lumateperone for bipolar disorder were reviewed. Additionally, pharmacodynamic actions of lumateperone are reviewed. Lumateperone is superior to placebo whether used alone or in combination with a mood stabilizer in patients with type I or type II bipolar disorder. It achieves this effect with minimal dopamine blockade-related side effects due to less than 50% dopamine D2 receptor occupancy. While the pharmacodynamic profile of lumateperone is unique, the mechanism of action in bipolar depression remains obscure.

Lumateperone is an antipsychotic with full antagonist effects at the post-synaptic D2, and partial agonist effects at the presynaptic D2. This unique profile allows for both antipsychotic and antidepressant effects at the same dose, which does not produce dopamine-related side effects. Consequently, lumateperone is exceptionally well tolerated compared to other antidepressant-acting antipsychotic agents. It is now the only agent approved as an adjunct to the mood stabilizer for bipolar II depression.