Pimavanserin
Second-generation antipsychotics
Second-generation antipsychotics
A 5-HT2A inverse agonist with no dopamine blockade, used for hallucinations and delusions of Parkinson disease psychosis without worsening movement.
Quick facts
- Group
- Second-generation antipsychotics
- Target
- Serotonin 5-HT2A receptor (inverse agonist)
- Used for
- Hallucinations
- Key effects
- Peripheral oedema · Confusion
- Monitor
- ECG in people with QT risk factors
- ATC
- N05AX17
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows pimavanserin bound to the human serotonin 5-HT2A receptor (fused to a small protein for crystallisation).
Pimavanserin is an inverse agonist and antagonist at serotonin 5-HT2A receptors, and to a lesser degree at 5-HT2C. It has no meaningful dopamine receptor binding. Because it does not block D2, it treats hallucinations and delusions in Parkinson disease psychosis without worsening parkinsonism, the problem with most antipsychotics in these patients.
- Pimavanserin switches off 5-HT2A receptors (inverse agonist)
- Less cortical 5-HT2A signalling: fewer hallucinations
- No D2 block: parkinsonism does not worsen
- Watch for QT prolongation
Indications
- Hallucinations and delusions associated with Parkinson disease psychosis Parkinson disease →
Adverse effects
Common
- Peripheral oedema (swollen legs)
- Confusion
Contraindications
- Hypersensitivity to pimavanserin
Key interactions
- Strong CYP3A4 inhibitors (ketoconazole, clarithromycin)
- Higher levels; the amount is reduced
- Strong or moderate CYP3A4 inducers (rifampicin, carbamazepine, phenytoin)
- Avoided: loss of effect
- Other QT-prolonging drugs (class Ia and III antiarrhythmics, some antipsychotics and antibiotics)
- Additive QT prolongation
What is monitored
- ECG in people with QT risk factors
- Swelling of the legs, confusion and falls
- Parkinson motor symptoms (should not worsen)
Administration and safety
- Capsules may be opened and mixed with a spoonful of soft food, eaten at once and not stored
- Its long half-life means effects fade slowly after stopping
Pregnancy and breastfeeding
Human data are very limited; use weighs benefit and risk.
Nursing care
- Records how often hallucinations and delusions occur, to judge the response
- Checks legs for swelling and watches for confusion and falls
- Reviews the medicine list for QT-prolonging drugs and CYP3A4 inhibitors or inducers
- Reports palpitations or fainting
Pharmacokinetics
- Absorption
- Taken by mouth; capsules can be opened onto soft food
- Metabolism
- Liver, mainly CYP3A4, to an active N-desmethyl metabolite
- Half-life
- About 57 hours (about 200 hours for the active metabolite)
Test yourself
Think of the answer, then tap the question to see it.
Why does pimavanserin not worsen parkinsonism?
It does not block dopamine receptors; it acts as an inverse agonist at 5-HT2A.
What is pimavanserin approved for?
Hallucinations and delusions of Parkinson disease psychosis.
Which ECG effect is a warning for pimavanserin?
QT prolongation.
Connections
← Back to the class: Second-generation antipsychotics
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - PIMAVANSERIN capsule (DailyMed (U.S. National Library of Medicine), 2026); Pimavanserin: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.