Milsaperidone

BYSANTI

What it isD2 and 5-HT2A antagonist with alpha-1 and hERG blockade; schizophrenia and bipolar mania.

Why it mattersIt rapidly interconverts with iloperidone and has closely similar efficacy and safety, leaving little clinical differentiation.

What it changesOrthostatic hypotension and QT prolongation shape titration and interaction review; sedation and weight gain also occur.

FDA-approved for

BOXED WARNING Increased mortality in elderly patients with dementia-related psychosis; not approved for dementia-related psychosis

FDA dosing	Population	Start	Target	Max
Schizophrenia	Adult	1 mg BID (Day 1)	6–12 mg BID	12 mg BID
Bipolar I (manic/mixed episodes)	Adult	1 mg BID (Day 1)	12 mg BID	12 mg BID
Schizophrenia	CYP2D6 poor metabolizer	1 mg BID (Day 1)	3–6 mg BID	6 mg BID
Bipolar I (manic/mixed episodes)	CYP2D6 poor metabolizer	1 mg BID (Day 1)	6 mg BID	6 mg BID

Titration Titrate daily per schedule (schizophrenia through Day 7; bipolar through Day 5) to reduce risk of orthostatic hypotension

Renal Undefined

Hepatic Mild: same as normal; moderate: consider lower maintenance dose; severe: not recommended

Restart titration if more than 3 days of treatment are missed

Take orally twice daily with or without food
If >3 days of doses missed, restart the titration schedule
With a strong CYP2D6 and/or CYP3A4 inhibitor, reduce dose by one-half; consider CYP2D6 genotyping

Schizophrenia: dizziness, dry mouth, fatigue, nasal congestion, orthostatic hypotension, somnolence, tachycardia, weight increased
Bipolar mania: tachycardia, dizziness, dry mouth, increased hepatic enzymes, nasal congestion, weight increased, hypotension, somnolence

Pregnancy Third-trimester antipsychotic exposure risks neonatal extrapyramidal/withdrawal symptoms; pregnancy exposure registry available

Lactation No human data; advise not to breastfeed during treatment and for 6 days (CYP2D6 normal) / 8 days (poor metabolizers) after last dose

⚠ BOXED WARNING