The antipsychotic triggered mania in three patients within two weeks
STUDY: Mudgal V et al, Indian Journal of Psychiatry 2026
STUDY TYPE: Case series
FUNDING: Independent
Background
Most antipsychotics are linked to mania in case reports. It’s a rare, paradoxical reaction, and one that is more concerning with antipsychotics that treat depression but have no anti-manic potential, like lurasidone (Latuda) and lumateperone (Caplyta).
Lumateperone combines serotonin 2A blockade, partial dopamine agonism, and mild serotonin reuptake inhibition.
The Cases
- Three adults with bipolar I or II disorder, all in a depressive episode and already on mood stabilizers or antipsychotics, started lumateperone 42 mg daily. Two were also taking an antidepressant, and one was taking fluoxetine (which elevates lumateperone’s levels).
- All developed manic symptoms within 10 to 14 days, with mania scale (YMRS) scores of 26 to 29, well into the severe range.
Practice Implications
- Watch out for this rare possibility, particularly in patients taking fluoxetine or other CYP3A4 inhibitors that raise lumateperone (and other antipsychotic) levels.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
