FDA Approves Milsaperidone for Treatment of Bipolar I Disorder and Schizophrenia

The FDA approved milsaperidone tablets (Bysanti; Vanda Pharmaceuticals) for the acute treatment of manic or mixed episodes associated with bipolar I disorder and the treatment of schizophrenia in adults.¹

Milsaperidone is a new chemical entity that belongs in the class of atypical antipsychotics. It is an active metabolite of iloperidone (Fanapt; Vanda Pharmaceuticals), a second-generation antipsychotic previously approved for schizophrenia and manic or mixed episodes associated with bipolar I disorder. In clinical trials, milsaperidone demonstrated bioequivalence to iloperidone across the therapeutic dosing spectrum, representing a novel therapeutic option with a trusted safety profile in these psychiatric indications.^1-3

Milsaperidone rapidly interconverts to iloperidone, providing dual active molecules that work in tandem by antagonizing dopamine D₂, serotonin 5-HT_2A, and α1-adrenergic receptors to modulate key pathways in these disorders. Its safety profile aligns closely with that established for iloperidone. Its unique in-class receptor binding profile, featuring strong α-adrenergic binding in excess of dopamine and serotonin receptor binding, makes it suitable for further investigation in conditions that include symptoms of hostility, agitation, and hyperarousal.^1-3

It is undergoing investigation as a once-daily adjunctive option in treatment-resistant major depressive disorder in an ongoing phase 3 clinical study (NCT06830044) expected to be completed by the end of 2026.^1,4

The most common adverse events (AEs) reported were fatigue, nasal congestion, orthostatic hypotension in schizophrenia, and increased hepatic enzymes and hypotension in bipolar I disorder. Dizziness, dry mouth, somnolence, tachycardia, and increased weight were AEs present in both schizophrenia and bipolar I disorder.³

Milsaperidone is available in 1-, 2-, 4-, 6-, 8-, 10-, and 12-mg doses and is administered twice per day with or without food.

"The [milsaperidone] approval marks a significant step forward, offering patients and providers a reliable new treatment grounded in extensive clinical heritage," Mihael H. Polymeropoulos, MD, president, CEO, and chairman of the board of Vanda Pharmaceuticals, said in a news release. "[Milsaperidone] exemplifies a new era of accelerated innovation in drug development that can transform how we address unmet needs in behavioral health."¹

REFERENCES

1. Vanda Pharmaceuticals announces FDA approval of Bysanti (milsaperidone) for the treatment of bipolar I disorder and schizophrenia - a new chemical entity opening new horizons in psychiatric innovation. News release. Vanda Pharmaceuticals. February 20, 2026. Accessed March 3, 2026. https://www.prnewswire.com/news-releases/vanda-pharmaceuticals-announces-fda-approval-of-bysanti-milsaperidone-for-the-treatment-of-bipolar-i-disorder-and-schizophrenia---a-new-chemical-entity-opening-new-horizons-in-psychiatric-innovation-302693941.html

2. de Quevedo JL. FDA approval of Bysanti (milsaperidone): a new option for bipolar I disorder and schizophrenia. McGovern Medical School. February 23, 2026. Accessed March 3, 2026. https://med.uth.edu/psychiatry/2026/02/23/fda-approval-of-bysanti-milsaperidone-a-new-option-for-bipolar-i-disorder-and-schizophrenia/

3. Bysanti (milsaperidone). Prescribing information; 2026. Accessed March 3, 2026. https://assets.vandapharma.com/Bysanti/Prescribing_Information.pdf

4. Evaluation of efficacy and safety of milsaperidone as adjunctive therapy in patients with major depressive disorder. ClinicalTrials.gov. Updated February 27, 2026. Accessed March 3, 2026. https://clinicaltrials.gov/study/NCT06830044