Pimavanserin (Nuplazid)

Class

Atypical antipsychotic, selective 5-HT2A inverse agonist/antagonist

Mechanism

Selective inverse agonist and antagonist at serotonin 5-HT2A receptors, with minimal to no dopamine receptor blockade, reducing extrapyramidal symptom risk

FDA-Approved Use

Parkinson’s disease psychosis (PDP)

Off-Label Use

Psychosis in other neurodegenerative disorders, adjunctive treatment in mood and psychotic disorders

Formulation

Oral tablets (17 mg)

Titration

34 mg p.o. daily (two 17 mg tablets), no titration required

Dose Range

34 mg/day

Kinetics

Metabolized primarily by CYP3A4; avoid concomitant use with strong CYP3A4 inhibitors or inducers; half-life ~55 hours

Common AEs

Peripheral edema, nausea, confusion

Serious/Rare AEs

QTc prolongation, neuropsychiatric worsening (hallucinations, delirium)

Monitoring

ECG monitoring for QTc prolongation risk, mental status monitoring for neuropsychiatric symptoms

Black Box Warning

Increased mortality in elderly patients with dementia-related psychosis unrelated to Parkinson’s disease

Considerations

Pimavanserin is particularly beneficial for managing psychosis in Parkinson’s disease due to its lack of dopamine receptor blockade, minimizing extrapyramidal symptoms. It is not recommended for elderly patients with dementia-related psychosis unrelated to Parkinson’s or Alzheimer’s disease because of increased mortality risk.