What is the treatment for Parkinson's psychosis?

October 10, 2025 •

2 min read

Up to 60% of people with Parkinson's disease (PD) will experience psychosis at some point during their illness. Understanding the question 'What is the treatment for Parkinson's psychosis?' involves a multi-step approach, from medication adjustments to targeted therapies.

Quick Summary

Management of Parkinson's disease psychosis begins with adjusting existing PD medications. Pimavanserin is the only FDA-approved drug, while off-label options like clozapine and quetiapine are also used.

Key Points

First Step is Review: The initial step in treating PDP is to rule out other medical causes and review and adjust the patient's current Parkinson's medications.
FDA-Approved Treatment: Pimavanserin (Nuplazid) is the only medication specifically approved by the FDA to treat psychosis in Parkinson's disease without worsening motor symptoms.
Off-Label Options Exist: Clozapine and quetiapine are atypical antipsychotics used off-label, but they have significant considerations, such as blood monitoring for clozapine and weaker efficacy for quetiapine.
Avoid Typical Antipsychotics: Traditional antipsychotics like haloperidol must be avoided as they block dopamine and can severely worsen Parkinson's motor functions.
Prevalence is High: Psychotic symptoms like hallucinations and delusions affect up to 60% of individuals with Parkinson's disease over the course of their illness.
Symptoms Vary: Symptoms range from minor phenomena like a sense of presence to fully formed visual hallucinations (most common) and delusions.
Non-Drug Strategies Help: Non-pharmacological approaches, such as improving room lighting, maintaining routines, and providing caregiver support, are important complementary strategies.

Understanding Parkinson's Disease Psychosis (PDP)

Parkinson's disease psychosis (PDP) is a common non-motor symptom characterized by hallucinations and delusions. Hallucinations are false sensory perceptions, most often visual, while delusions are false, fixed beliefs. These symptoms can arise from the progression of PD or as a side effect of medications that increase dopamine to manage motor symptoms.

Initial Management: A Stepwise Approach

Treating PDP starts with a clinical evaluation to rule out other causes like infections. Next, physicians review PD medications, aiming to reduce those contributing to psychosis without worsening motor function. This process typically involves adjusting anticholinergics, amantadine, and MAO-B inhibitors before considering dopamine agonists and levodopa.

Pharmacological Treatments for PDP

If adjusting PD medications is insufficient, antipsychotic medication may be prescribed.

Pimavanserin (Nuplazid): The FDA-Approved Standard

Pimavanserin (Nuplazid) is the only FDA-approved medication for hallucinations and delusions in PDP. It works differently from traditional antipsychotics by targeting serotonin receptors, reducing psychosis without worsening motor symptoms. Side effects can include swelling and confusion. It carries a warning about increased death risk in elderly patients with dementia-related psychosis.

Off-Label Antipsychotic Options

Other atypical antipsychotics are used off-label for PDP.

Clozapine (Clozaril): Effective for PDP without worsening motor symptoms, but requires regular blood monitoring due to the risk of agranulocytosis.
Quetiapine (Seroquel): Often used due to fewer side effects and no blood monitoring requirement, though evidence of its efficacy compared to placebo is mixed. It is frequently used at bedtime for its sedating effect.

Medications to Avoid

Typical antipsychotics like haloperidol and risperidone should not be used in PD patients. They block dopamine receptors, which can severely worsen motor symptoms.

Comparison of Common PDP Medications


Medication	FDA Approval for PDP	Mechanism	Effect on Motor Symptoms	Key Risks & Monitoring
Pimavanserin (Nuplazid)	Yes	Selective Serotonin Inverse Agonist	Does not worsen motor symptoms	Peripheral edema, confusion; Boxed warning for elderly with dementia-related psychosis.
Clozapine (Clozaril)	No (Off-label use)	Atypical Antipsychotic	Does not typically worsen motor symptoms	Risk of agranulocytosis requires frequent blood monitoring; sedation, weight gain, seizures.
Quetiapine (Seroquel)	No (Off-label use)	Atypical Antipsychotic	Generally well-tolerated, low risk of worsening motor symptoms	Limited evidence for efficacy; sedation, orthostatic hypotension, dizziness.

Non-Pharmacological Management

Non-drug strategies complement medication in managing PDP. These include:

Environmental Adjustments: Good lighting can reduce visual misperceptions. Consistent routines can also be helpful.
Caregiver Support: Care partners can learn reassuring ways to respond to hallucinations.
Therapeutic Activities: Engaging activities, music, and exercise may improve well-being.

Conclusion

Treating Parkinson's disease psychosis requires an individualized, multi-step approach. It starts with addressing reversible causes and adjusting PD medications. Pimavanserin, the only FDA-approved option, is preferred for its ability to treat psychosis without worsening motor function. Off-label alternatives like clozapine and quetiapine are used with caution due to their side effect profiles. Typical antipsychotics are contraindicated. A comprehensive approach combining medication with non-pharmacological support is essential for improving the quality of life for those with PDP and their caregivers. Consult with a healthcare team for treatment decisions.

For further reading, visit the Parkinson's Foundation.

Frequently Asked Questions

The first-line treatment is to review and, if possible, adjust the patient's current Parkinson's medications to see if they are causing the psychotic symptoms. This involves reducing or stopping certain drugs in a specific order under a doctor's supervision.

Pimavanserin (brand name Nuplazid) is the only medication approved by the U.S. Food and Drug Administration (FDA) specifically for the treatment of hallucinations and delusions associated with Parkinson's disease psychosis.

Typical antipsychotics like haloperidol and risperidone are avoided because they block dopamine receptors. This action can severely worsen the primary motor symptoms (like stiffness and slowness) of Parkinson's disease.

Yes, clozapine has been shown to be effective in treating psychosis in Parkinson's disease without worsening motor symptoms. However, it carries a rare but serious risk of agranulocytosis (a severe drop in white blood cells) and requires regular blood monitoring.

Yes, non-pharmacological approaches can be helpful. These include ensuring good lighting to reduce visual errors, maintaining a regular schedule, and using reassuring communication techniques. These strategies can complement medical treatment.

The most common symptoms are visual hallucinations (seeing things that aren't there). Other symptoms include delusions (firm, false beliefs, often of a paranoid nature), illusions (misperceiving real objects), and a sense of presence (feeling someone is nearby).

Quetiapine is frequently used off-label because it has a low risk of worsening motor symptoms and does not require blood monitoring. However, clinical trials have shown limited and inconsistent evidence of its effectiveness compared to a placebo.