Brands: Bysanti
Sources updated 2026 • 5 references
At a glance
- Class
- Antipsychotic
- Category
- Antipsychotic
- Typical dose
- Schizophrenia titration (adults): Day 1 1 mg BID → Day 2 2 mg BID → Day 3 4 mg BID → Day 4 6 mg BID → Day 5 8 mg BID → Day 6 10 mg BID → Day 7 12 mg BID; maintenance target 6–12 mg BID.
- Half-life
- Single-dose mean 26 h; Steady-state mean 33 h
- LAI available
- No
- Last reviewed
- 2026-02-28
General information
Milsaperidone (brand BYSANTI) is a second-generation antipsychotic approved by the FDA in February 2026 for adult schizophrenia and acute manic or mixed episodes associated with bipolar I disorder.
It is the active metabolite of iloperidone (Fanapt) and interconverts with iloperidone in vivo, sharing potent antagonism at dopamine D2, serotonin 5-HT2A, and adrenergic α1 receptors, which necessitates a structured titration schedule to mitigate orthostatic hypotension and syncope.
Tablet strengths from 1 mg to 12 mg enable fine-tuned dosing; therapy must restart at 1 mg twice daily if treatment is interrupted for three or more consecutive days.
The compare tool, the evidence library, and the Schizophrenia hub support side-by-side review of related SGAs and follow-up planning.
U.S. approvals
- Schizophrenia (adults) (2026)
- Acute manic/mixed episodes in bipolar I disorder (adults) (2026)
Formulations & strengths
- Tablets: 1 mg, 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, 12 mg.
Generic availability
- No generic available. BYSANTI is a new chemical entity marketed by Vanda Pharmaceuticals with commercial availability expected Q3 2026.
Milsaperidone's dual-indication approval for both schizophrenia and bipolar I mania broadens its clinical role compared to iloperidone. Like iloperidone, use is tempered by slow titration and QTc warnings; however, the additional bipolar indication may favor milsaperidone when mood stabilization is a treatment goal.
View labelExactMechanism of action
Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.
Antagonism at dopamine D2 and serotonin 5-HT2A receptors delivers antipsychotic efficacy with a comparatively low EPS profile.
High affinity for α1-adrenergic receptors underlies orthostatic hypotension and reflex tachycardia. Additional serotonin receptor antagonism (5-HT6, 5-HT7) may support cognitive and mood effects.
- Shares the receptor-binding profile of its parent compound iloperidone, including high affinity at α1, 5-HT2A, D2, and D3 receptors.
- Minimal muscarinic and histaminergic activity limits anticholinergic side effects.
Metabolism & pharmacokinetics
- Milsaperidone is the active metabolite of iloperidone; the two compounds interconvert in vivo. Oral bioavailability is high with peak concentrations 2–4 hours after dosing.
- Metabolized primarily via CYP2D6 and CYP3A4; elimination half-life averages 26 hours in extensive metabolizers and approximately 37 hours in CYP2D6 poor metabolizers.
- Steady state is achieved within 3–4 days. Approximately 45% of drug-related material is recovered in urine and 50% in feces; protein binding is approximately 95%.
- CYP2D6 poor metabolizers (7–10% of Caucasians) exhibit roughly double the exposure; dose reduction by 50% is recommended. Hepatic impairment increases exposure and warrants slower titration and close monitoring.
Dosing & administration
- Schizophrenia titration (adults): Day 1 1 mg BID → Day 2 2 mg BID → Day 3 4 mg BID → Day 4 6 mg BID → Day 5 8 mg BID → Day 6 10 mg BID → Day 7 12 mg BID; maintenance target 6–12 mg BID.
- Bipolar I mania titration (adults): Day 1 2 mg BID → Day 2 4 mg BID → Day 3 8 mg BID → Day 4 10 mg BID → Day 5 12 mg BID; target 12 mg BID.
- CYP2D6 poor metabolizers or strong CYP2D6 inhibitor co-therapy (fluoxetine, paroxetine, quinidine, bupropion): target and maximum doses are typically reduced by 50%.
- Strong CYP3A4 inhibitors (ketoconazole, clarithromycin, itraconazole): dose reduction by ~50% is common, with monitoring for QTc prolongation often considered.
- Strong CYP3A4 inducers (carbamazepine, rifampin, St. John's wort): serum levels can drop significantly, risking relapse, so combinations are generally avoided.
- If therapy is interrupted for ≥3 consecutive days, titration is typically restarted from 1 mg BID to reduce hypotension risk.
- Administration: Twice-daily dosing with or without food; bedtime dosing of a larger portion may reduce orthostatic symptoms.
Adverse effects
FDA boxed warnings
- Antipsychotics increase mortality in elderly patients with dementia-related psychosis; milsaperidone is not approved for this population.
Common side effects (≥10%)
- Tachycardia: The most frequently reported adverse effect; heart rate increases are common especially during titration and with concomitant QTc-prolonging drugs.
- Dizziness and orthostatic hypotension: Most pronounced during titration; counseling often includes hydration and slow position changes.
- Dry mouth: Common; supportive care is usually sufficient.
- Somnolence: May improve after the first week; some dosing strategies shift a larger portion to bedtime when tolerated.
- Weight gain: Modest average gain is expected; routine metabolic labs are still typically obtained.
Other notable effects
- QTc prolongation—baseline ECG is often considered in at-risk patients, and minimizing additive QTc drugs can reduce overall risk.
- Low-to-moderate risk of akathisia or EPS—ongoing monitoring is still common despite a favorable profile.
- Rare neuroleptic malignant syndrome or tardive dyskinesia warrant prompt evaluation if rigidity or new movements emerge.
Interactions
- Strong CYP2D6 inhibitors or poor metabolizer status often require halving the milsaperidone dose.
- Strong CYP3A4 inhibitors elevate exposure—dose reduction by ~50% is common, with QTc monitoring often considered.
- Strong CYP3A4 inducers can markedly reduce serum levels and are generally avoided due to potential loss of efficacy.
- Additive QTc prolongation with drugs such as amiodarone, sotalol, or methadone; ECG monitoring is often considered or alternatives may be preferred.
- Concomitant antihypertensives, alcohol, or CNS depressants may potentiate hypotension and sedation.
Other useful information
- Orthostatic vitals are often checked at baseline, during titration, and after dose increases.
- Patient education often includes restarting titration if therapy is interrupted and reporting presyncope, palpitations, or dizziness.
- Milsaperidone is the active metabolite of iloperidone; clinicians familiar with iloperidone's safety profile will find substantial overlap in monitoring requirements.
- Routine metabolic monitoring is continued; pregnancy risk should be discussed as limited human data are available.