An Evaluation of Iloperidone for Mania in Bipolar I Disorder.

Objective: To review the efficacy of iloperidone for mania associated with bipolar I disorder and discuss its safety profile (eg, QTc prolongation, orthostatic hypotension, and metabolic adverse effects).

Data sources: Literature was identified using PubMed (1966-September 2024), OVID (1984-November 2024), and clinicaltrials.gov. Search terms included iloperidone, bipolar disorder, and mania.

Study selection and data extraction: The study included trials evaluating iloperidone for treating bipolar mania.

Data synthesis: In one phase 3 study, iloperidone demonstrated significant improvement in mania symptoms at day 28 on all primary (ie, Young Mania Rating Scale) and secondary outcomes (Clinical Global Impression-Severity/Change scales) compared to placebo. Iloperidone was well tolerated, with tachycardia, dizziness, dry mouth, alanine aminotransferase elevation, nasal congestion, increased weight, and somnolence reported as common adverse effects.

Relevance to patient care and clinical practice in comparison to existing drugs: Since there are no head-to-head studies comparing iloperidone with other second-generation antipsychotics for bipolar mania, other treatment considerations drive medication selection. Iloperidone is unavailable in a generic formulation; thus, its use will be associated with higher costs. It is dosed twice daily, which may negatively impact adherence. Iloperidone is associated with a moderate risk of QTc prolongation, metabolic adverse effects, and orthostatic hypotension, which will limit its use in certain patient populations. QTc prolongation is dose related, so drug interactions involving CYP2D6 and CYP3A4 inhibition can have serious consequences.

Conclusion: In the pivotal trial, iloperidone was effective in treating adults with an acute manic or mixed episode associated with bipolar I disorder and was safe and well tolerated.