ABSTRACT
Introduction
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.
Areas covered
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.
Expert opinion
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.
Article highlights
There remains an unmet need for safe and effective antidepressant agents in bipolar disorder, particularly for adjunctive use with a mood stabilizer
Lumateperone has recently been approved by the United States Food and Drug Administration for use as both monotherapy and add-on to lithium or valproic acid for the treatment of a major depressive episodes in type I and II bipolar disorders.
Lumateperone is associated with minimal Parkinsonism, akathisia, and prolactin-related issues, even though it is used at its full antipsychotic dose.
Lumateperone has also demonstrated no real changes in weight, lipids, glucose, and insulin, even with 6 months of exposure.
Lumateperone has a unique pharmacodynamic profile with antagonism at the post-synaptic D2 receptor, partial agonism at the presynaptic D2 receptor, and a possible agonist effect at D1 receptor.
Declaration of interest
R El-Mallakh is a speaker for Axsome, Intracellular Therapeutics, Janssen Pharmaceuticals, Lundbeck, Myriad, Noven, Otsuka, and Teva Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.