FDA Approves Iloperidone (Fanapt) for Acute Treatment of Bipolar I Disorder

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The FDA approved iloperidone for acute treatment of bipolar I disorder on April 02, 2024, according to Vanda Pharmaceuticals.

The US Food and Drug Administration (FDA) has approved iloperidone (Fanapt) for the acute treatment of bipolar I disorder.1

Announced by Vanda Pharmaceuticals on April 2, 2024, the FDA decision was based on the findings of a phase 3, randomized, double-blind placebo-controlled study, which found iloperidone demonstrated significant improvement compared to placebo at week 4 for the primary and secondary endpoints, with the safety and tolerability comparable to symptoms found in other clinical studies.

"Manic or mixed episodes associated with bipolar I disorder are highly complex conditions, which require a host of trusted options to meet individual patient needs. With over 100,000 patient years of experience, Fanapt is a familiar therapeutic agent that offers flexible dosing with a well-known safety profile. This FDA approval gives patients and service providers a new treatment option for managing bipolar I disorder," said Mihael H. Polymeropoulos MD, Vanda's President, chief executive officer and chairman.

The phase 3 study, led by Rosarelis Torres, PhD, from Vanda Pharmaceuticals, evaluated the effects of iloperidone in adults with bipolar mania at 27 US and international sites between April 2021 and September 2022.2

Back in 2009, the FDA approved Iloperidone for the treatment of schizophrenia in adults, supported by 2 phase 3 placebo-controlled trials showing iloperidone at doses of 12 mg and 24 mg per day was superior to placebo.3 The approval followed roughly 10 months after the FDA rejected Vanda Pharmaceutical’s new drug application (NDA) for iloperidone after questions surrounding the drug’s efficacy relative to risperidone.4

It was not until Vanda Pharmaceutical’s conducted another clinical trial comparing iloperidone with ziprasidone and resubmitted the NDA that the FDA approved iloperidone for schizophrenia.5 Since iloperidone originally did not demonstrate superior efficacy over risperidone, the benefits of iloperidone were debated. Some investigators argued, despite risperidone having superior efficacy, patients have varying responses to drugs.

Despite the controversy over iloperidone for schizophrenia, the trials evaluating iloperidone for bipolar disorder showed positive results. The study brought significant improvements at week 4 for the primary and secondary endpoints.

The trial used in support of the application for bipolar I disorder included 414 participants aged with 18 to 65 years a diagnosis of bipolar I disorder, with or without mixed features, in accordance with DSM-5 criteria. Patients included were randomized to iloperidone (n = 206) and placebo (n = 208). In total, 67.1% of iloperidone patients and 72.9% of placebo patients completed the study.

The primary endpoint was a change in baseline to week 4 in the Young Mania Rating Scale total score versus placebo, and the secondary endpoints included a change from baseline in the scales Clinical Global Impressions-Severity and Clinical Global Impression of Change.

Investigators observed a mean change from baseline for the Young Mania Rating Scale total scores of – 4.0 (95% confidence interval [CI], -5.70 to – 2.25; P = .000008). They also saw statistically significant differences between iloperidone and placebo by day 28 in the change from baseline of the Clinical Global Impressions-Severity and Clinical Global Impression of Change scales.

Common adverse events included tachycardia, dizziness, dry mouth, increased alanine aminotransferase, nasal congestion, weight gain, and somnolence. There was low akathisia and extrapyramidal symptom-related treatment-emergent adverse events.

According to the Mayo Clinic, iloperidone may cause other, less common adverse events, such as blurred vision, body aches, chills, cold sweats, confusion, and more.6

"Today's announcement marks a significant step forward for one of Vanda's leading franchises and underscores the effectiveness of our strategy in pursuing innovative therapies that address high unmet medical needs to improve the lives of patients. With this as our foundation, we have established a resilient business, with a diverse product pipeline, a history of revenue growth and strong financial position. We remain focused on providing critical medicines to patients across the world while creating sustainable, long-term value."1


  1. Vanda Pharmaceuticals. Vanda Pharmaceuticals’ Fanapt® (iloperidone) Receives U.S. FDA Approval for the Acute Treatment of Bipolar I Disorder. Vanda Pharmaceuticals Recent News. April 2, 2024. Accessed April 2, 2024.
  2. Torres R, Czeisler EL, Chadwick SR, et al. Efficacy and Safety of Iloperidone in Bipolar Mania: A Double-Blind, Placebo-Controlled Study. J Clin Psychiatry. 2024;85(1):23m14966. Published 2024 Jan 15. doi:10.4088/JCP.23m14966
  3. FDA Approves Vanda Pharmaceuticals' Fanapt(TM) for the Treatment of Schizophrenia. Vanda Pharmaceuticals. May 6, 2009. Accessed March 28, 2024.
  4. FDA Reverses Earlier Decision, Approves Schizophrenia Drug. Psychiatric News. 2009.
  5. Bender, K. Iloperidone Approved as “Second-Generation” Benefits Debated. Pscyhiatric Times. August 24, 2009. Accessed March 28, 2024.
  6. Iloperidone (Oral Route). Mayo Clinic. Accessed March 28, 2024.