pimavanserin
Last reviewed 2025-12-30
Reviewed by PsychMed Editorial Team.
Brands: Nuplazid
Sources updated 2025 • 4 references
General Information
Pimavanserin (brand Nuplazid) is approved for hallucinations and delusions associated with Parkinson’s disease psychosis (PDP) (label).
Unlike most antipsychotics, pimavanserin does not meaningfully block dopamine receptors. This matters in Parkinson’s disease because D2 blockade can worsen motor symptoms; pivotal trials found improvement in psychosis without worsening motor ratings compared with placebo (label/trial).
Pimavanserin carries the antipsychotic boxed warning about increased mortality in elderly patients with dementia-related psychosis and is not approved for dementia-related psychosis unless symptoms are related to Parkinson’s disease (label).
QT prolongation is a key safety consideration; baseline risk review and interaction checks are typically part of prescribing (label/clinical).
In clinical practice, management of PDP often includes addressing reversible contributors (infection, medication changes, sleep disruption) and considering off-label antipsychotics; pimavanserin is often selected when avoiding dopamine blockade is a priority (review/clinical).
Response is typically assessed over several weeks, with reassessment of diagnosis, triggers, and safety (falls/confusion) if symptoms do not improve (clinical).
The compare view, pimavanserin evidence feed, and pimavanserin print page support documentation and counseling when treatment choices overlap with sedation, falls, and QT concerns.
U.S. approvals
- Hallucinations and delusions associated with Parkinson’s disease psychosis (label) ()
Formulations & strengths
- Oral capsule (label): 34 mg.
- Oral tablet (label): 10 mg.
Generic availability
- Brand-only in the U.S. (no generic equivalent).
Often used when PDP symptoms are distressing and when avoiding dopamine blockade is a priority. Safety planning frequently focuses on QT risk, confusion/delirium risk, and drug interactions via CYP3A4.
View labelExactMechanism of Action
Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.
Selective serotonin 5-HT2A inverse agonist/antagonist with minimal dopamine receptor activity, targeting psychosis symptoms without the typical motor side effects of D2 blockade (label/mechanism).
5-HT2A modulation is relevant to psychosis in Parkinson’s disease and related neurodegenerative disorders (mechanism).
- 5-HT2A inverse agonism/antagonism; minimal D2 activity.
Metabolism and Pharmacokinetics
- Predominantly metabolized by CYP3A4 and CYP3A5, with minor contributions from CYP2J2 and CYP2D6 (label).
- Label notes a long plasma half-life of pimavanserin (about 57 hours), supporting once-daily dosing and prolonging washout considerations (label).
- Low unchanged drug recovery in excreta (approximately 0.55% in urine and 1.53% in feces after radiolabeled dosing) (label).
Dosing and Administration
- Recommended dose is 34 mg once daily without titration (label).
- When co-administered with strong CYP3A4 inhibitors, the recommended dose is reduced to 10 mg once daily (label).
- Avoid concomitant strong or moderate CYP3A4 inducers because exposure is reduced (label).
Monitoring & Labs
- Review baseline QT risk (history of arrhythmia/syncope, electrolyte abnormalities) and other QT-prolonging drugs; consider an ECG when risk is elevated (label/clinical).
- Monitor for confusional state/delirium, peripheral edema, and falls, especially in older adults with baseline cognitive impairment (label/clinical).
- Reassess hallucinations/delusions and caregiver distress after initiation (often within the first month) and after major medication changes (clinical).
- Medication reconciliation: avoid strong CYP3A4 inducers, reduce dose with strong CYP3A4 inhibitors, and re-check interactions when new medicines are started (label).
- If switching from another antipsychotic, use a structured cross-taper plan and monitor for rebound psychosis or withdrawal effects (consensus/clinical).
Adverse Effects
FDA boxed warnings
- Increased mortality in elderly patients with dementia-related psychosis treated with antipsychotic drugs; Nuplazid is not approved for dementia-related psychosis unless hallucinations/delusions are related to Parkinson’s disease (label).
Common side effects (≥10%)
- Peripheral edema: Common in PDP trials; clinicians often monitor for swelling, weight change, and fall risk in older adults (label/clinical).
- Confusional state: Confusion can occur; monitoring often focuses on delirium risk, functional decline, and medication contributors (label/clinical).
- QT prolongation: Pimavanserin can prolong QT interval; avoid additive QT-prolonging combinations when possible and consider ECG monitoring in higher-risk patients (label/clinical).
Other notable effects
- Falls and frailty risks are often assessed in parallel because PDP populations are older and vulnerable to sedation/confusion even when dopamine blockade is avoided (clinical).
Interactions
- CYP3A4 inhibitors increase exposure and require dose reduction; CYP3A4 inducers reduce exposure and are avoided (label).
- QT-prolonging drugs can add risk; risk-benefit review is typical when co-use is unavoidable (label/clinical).
Other Useful Information
- Trials and reviews describe improvement in PDP psychosis symptoms with minimal motor worsening compared with placebo (trial/review).
- Expert consensus describes structured switching approaches from off-label antipsychotics to pimavanserin when motor side effects or sedation are a concern (consensus).
References
- NUPLAZID (pimavanserin tartrate) prescribing information — DailyMed (2025)
- Pimavanserin FOR Patients With Parkinson's Disease Psychosis: A Randomised, Placebo Controlled Phase 3 Trial — Lancet (2014)
- Evidence Based Review OF Pharmacotherapy Used FOR Parkinson's Disease Psychosis — The Annals of Pharmacotherapy (2017)
- Guidance FOR Switching From OFF Label Antipsychotics TO Pimavanserin FOR Parkinson's Disease Psychosis: AN Expert Consensus — CNS Spectrums (2018)