Pimavanserin

NUPLAZID

What it isSelective 5-HT2A inverse agonist with no dopamine blockade; Parkinson-disease psychosis.

Why this oneIts lack of D2 blockade treats Parkinson psychosis without directly worsening motor function.

What limits itOnset is delayed. QT prolongation and CYP3A4 interactions constrain prescribing.

FDA-approved for

BOXED WARNING Increased mortality in elderly patients with dementia-related psychosis treated with antipsychotics.

FDA dosing	Population	Start	Target	Max
Hallucinations & delusions of Parkinson's disease psychosis	Adult	34 mg QD	34 mg QD	34 mg QD

Renal No adjustment for mild-severe impairment or ESRD; use with caution in severe impairment/ESRD

Hepatic No adjustment needed

Take once daily with or without food, without titration
Capsules may be swallowed whole or opened and sprinkled over a tablespoon of soft food; consume immediately without chewing

QT interval prolongation — avoid with other QT-prolonging drugs and in patients with QT risk factors, arrhythmia history, bradycardia, hypokalemia, or hypomagnesemia

Pregnancy No human data; animal maternal toxicity and lower pup survival/weight at ≥2x MRHD.

Lactation No information on presence in human milk or effects on breastfed infant.

⚠ BOXED WARNING

Cost, est. cash$300–$2,500/month

Generic entry2029+ est.

Therapeutic safety burden2 / 4

Overdose danger2 / 4

Weight-gain liability1 / 4

Sedation liability1 / 4

QT / Torsades2 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk2 / 4

Legacy pregnancy categoryNot assigned — PLLR-era drug

Defining liabilityMetabolic effects, extrapyramidal symptoms/tardive dyskinesia and agent-specific QT or orthostatic risk.

CYP3A4 substrate