Pimavanserin is a unique antipsychotic with a very specific niche in clinical practice. It is most commonly used for Parkinson’s disease psychosis, and its pharmacology, benefits, and risks are frequently tested and clinically misunderstood. In this blog post, I’ll share the most important pimavanserin practice pearls.

Dopamine Blocker? Nope…

Unlike traditional and atypical antipsychotics, pimavanserin does not block dopamine receptors (excellent board exam nugget). It acts as an inverse agonist and antagonist at serotonin 5-HT2A receptors, with minor activity at 5-HT2C receptors. This is why pimavanserin can treat psychosis without worsening motor symptoms in Parkinson’s disease. This is the primary utility of this medication.

QT Prolongation

While not a traditional antipsychotic, it is similar to other antipsychotics in that pimavanserin can prolong the QT interval. This risk is increased in patients with baseline QT prolongation, electrolyte abnormalities, or those taking other QT-prolonging medications. Consider baseline ECG in high-risk patients and correct potassium and magnesium abnormalities before initiation.

Boxed Warning

Like other antipsychotics, pimavanserin carries a boxed warning for increased mortality in elderly patients with dementia-related psychosis. Although it does not block dopamine, the warning still applies. Use pimavanserin only for appropriate indications and ensure risk–benefit discussions are documented.

Pimavanserin Drug Interactions

Pimavanserin is metabolized primarily by CYP3A4. Strong CYP3A4 inhibitors may increase drug levels, while strong inducers may reduce effectiveness. Dose adjustments or avoidance may be necessary when used with certain antifungals, macrolides, or anticonvulsants. This is one of my major concerns when this medication is used in our polypharmacy, geriatric patients.

Drug Cost and Insurance Coverage

Pimavanserin is very expensive, with some estimates as high as 80$ per day. Insurance coverage may be limited or patients may have to try and fail other medications (I.e. Seroquel) before insurance will allow it to be covered. This is a major reason why it is hard to recommend this medication for some patients.

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