Pimavanserin: Difference between revisions
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| pregnancy = Limited data; avoid | | pregnancy = Limited data; avoid | ||
| legal = Rx. FDA black-box warning for increased mortality in elderly patients with dementia-related psychosis (class warning shared with all antipsychotics) | | legal = Rx. FDA black-box warning for increased mortality in elderly patients with dementia-related psychosis (class warning shared with all antipsychotics) | ||
| intro = '''Pimavanserin''' (brand name Nuplazid) is the only FDA-approved | | intro = '''Pimavanserin''' (brand name Nuplazid) is the only FDA-approved medicine for the treatment of hallucinations and delusions in Parkinson's disease psychosis (approved April 2016). Unlike every other approved antipsychotic, it has '''no D2 dopamine receptor activity''' — a critical feature in Parkinson's, where conventional D2 antagonists worsen motor symptoms. Mechanism: selective 5HT2A inverse agonism with weaker 5HT2C inverse agonism. Carries the class black-box warning for increased mortality when used in elderly dementia-related psychosis, though it has been studied in that population and is investigational for dementia psychosis. Also studied as augmentation for major depression with positive preliminary results. | ||
| pharmacodynamics= Selective 5HT2A inverse agonist (Ki ~0.4 nM). Weaker 5HT2C inverse agonism. No significant binding at D2, muscarinic, adrenergic, or histaminergic receptors. The lack of D2 activity preserves dopaminergic function (essential in PD) while reducing the 5HT2A-mediated psychotic symptoms. | | pharmacodynamics= Selective 5HT2A inverse agonist (Ki ~0.4 nM). Weaker 5HT2C inverse agonism. No significant binding at D2, muscarinic, adrenergic, or histaminergic receptors. The lack of D2 activity preserves dopaminergic function (essential in PD) while reducing the 5HT2A-mediated psychotic symptoms. | ||
| effects = Peripheral edema, confusion, nausea, constipation, gait disturbance, hallucinations (paradoxically reported), QT prolongation (avoid combination with other QT-prolonging | | effects = Peripheral edema, confusion, nausea, constipation, gait disturbance, hallucinations (paradoxically reported), QT prolongation (avoid combination with other QT-prolonging medicines). | ||
| interactions = <pharmaInteractions/> | | interactions = <pharmaInteractions/> | ||
}} | }} | ||
Revision as of 02:27, 16 May 2026
Selective 5HT2A inverse agonist (with weaker 5HT2C inverse agonism)
Pimavanserin
Nuplazid
Pimavanserin (brand name Nuplazid) is the only FDA-approved medicine for the treatment of hallucinations and delusions in Parkinson's disease psychosis (approved April 2016). Unlike every other approved antipsychotic, it has no D2 dopamine receptor activity — a critical feature in Parkinson's, where conventional D2 antagonists worsen motor symptoms. Mechanism: selective 5HT2A inverse agonism with weaker 5HT2C inverse agonism. Carries the class black-box warning for increased mortality when used in elderly dementia-related psychosis, though it has been studied in that population and is investigational for dementia psychosis. Also studied as augmentation for major depression with positive preliminary results.
Selective 5HT2A inverse agonist (Ki ~0.4 nM). Weaker 5HT2C inverse agonism. No significant binding at D2, muscarinic, adrenergic, or histaminergic receptors. The lack of D2 activity preserves dopaminergic function (essential in PD) while reducing the 5HT2A-mediated psychotic symptoms.
Experience
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Problems
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Effects
Peripheral edema, confusion, nausea, constipation, gait disturbance, hallucinations (paradoxically reported), QT prolongation (avoid combination with other QT-prolonging medicines).
Pharmacodynamics
Interactions
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Relevant Literature
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Pharmacy
Starting dose
34 mg PO once daily
Preparations
10 mg, 34 mg capsules/tablets
US FDA Max
34 mg/d
Common uses
Classification(s)
Classes
Selective 5HT2A inverse agonist (with weaker 5HT2C inverse agonism)
Pharmacology
Routes
Oral
Onset
Benefit over weeks of dosing
Duration
Daily dosing
Half-life
~57 hours (parent), ~200 h (active metabolite)
Bioavailability
Not characterized; oral dosing once daily
Pregnancy
Limited data; avoid
Legal status
Rx. FDA black-box warning for increased mortality in elderly patients with dementia-related psychosis (class warning shared with all antipsychotics)
Purported mechanism
Selective inverse agonist at 5HT2A receptors with weaker activity at 5HT2C. Has no significant dopamine D2 affinity — unique among approved antipsychotics. Inverse agonism (rather than antagonism) reduces constitutive 5HT2A receptor activity below baseline.