The U.S. Food and Drug Administration (FDA) has expanded the approval for iloperidone (Fanapt®, Vanda) to include the acute treatment of mixed or manic episodes associated with bipolar I disorder in adults. Iloperidone is also indicated for the treatment of schizophrenia in adults.
The expanded approval of iloperidone was based on data from a phase 3 study that evaluated the efficacy and safety of iloperidone in 414 participants (mean age, 43 years; 56% male) across 17 US and international sites. Patients were randomly assigned to receive either a fixed daily oral of 24 mg of iloperidone (n = 206) or placebo (n=208) for 28 days.
The study findings showed patients treated with iloperidone had significantly larger improvements vs placebo based on the change from baseline in the Young Mania Rating Scale (YMRS) total score at week 4 (primary endpoint; treatment difference: -4.0 [95% CI, -5.7, -2.25]; P = 0.000008). The treatment group also reported significant decreases on the on the Clinical Global Impressions-Severity scale (mean, -0.4; P =.0005) and Clinical Global Impression of Change scale (mean, -0.5; P =.0002). Statistically significant differences between iloperidone and placebo were observed as early as day 14 and continued through days 21 and 28.
The safety profile of iloperidone was found to be consistent with previous trials in patients with schizophrenia. The most common adverse reactions reported were tachycardia, dizziness, dry mouth, increased alanine aminotransferase, nasal congestion, weight gain, and somnolence.
Iloperidone (Figure) has 5HT2A/D2 antagonist properties. Its other prominent pharmacological property is potent a1 antagonism, which may be responsible for the risk of orthostatic hypotension but also may contribute to its low risk of drug-induced parkinsonism (DIP). Its most distinguishing clinical properties include a very low level of motor side effects, low level of dyslipidemia, and moderate level of weight gain associated with its use.