Aripiprazole (Abilify) Should NOT Be Used for Psychosis in Parkinson's Disease
Do not use aripiprazole (Abilify) to treat psychotic symptoms in patients with Parkinson's disease, as it worsens motor symptoms and is explicitly excluded from recommended treatment options by major guidelines. 1, 2
Why Aripiprazole Is Contraindicated
The American Geriatrics Society specifically identifies only three antipsychotics as acceptable for Parkinson's disease psychosis: pimavanserin, quetiapine, and clozapine—aripiprazole is not among them. 1
All other antipsychotics, including aripiprazole, should be avoided as they worsen motor symptoms in Parkinson's disease. 1
Clinical trial evidence demonstrates that aripiprazole causes significant motor deterioration in PD patients: In an open-label pilot study, 8 of 14 patients (57%) discontinued aripiprazole due to worsened Parkinsonism (3 patients), worsened psychosis (2 patients), or both (2 patients), despite starting at only 1 mg/day and titrating to a maximum of 5 mg. 3
Recommended Treatment Algorithm for Parkinson's Disease Psychosis
Step 1: Address Reversible Causes First
- Rule out infectious, toxic, and metabolic causes of psychosis before starting antipsychotics. 4
- Systematically reduce anti-Parkinson's medications in this order: anticholinergics first, then MAO-B inhibitors, amantadine, dopamine agonists, COMT inhibitors, and lastly carbidopa/levodopa. 5
Step 2: Choose Appropriate Antipsychotic Therapy
First-line choice: Quetiapine 2
- Start with 25 mg at bedtime and increase gradually as needed. 2
- Most commonly used in clinical practice due to tolerability and ease of use, despite limited controlled trial evidence. 6, 7
Second-line choice: Clozapine 2, 4
- Use if blood monitoring is acceptable to the patient. 2
- Has the strongest evidence for efficacy without worsening motor symptoms and is the only antipsychotic proven effective in double-blind controlled trials. 6, 8
- Requires regular monitoring for agranulocytosis. 7
Third-line choice: Pimavanserin 2
- Specifically FDA-approved for Parkinson's disease psychosis. 2
- Has strong evidence for efficacy without motor worsening. 1
Critical Safety Considerations
Never use typical antipsychotics (haloperidol, fluphenazine) or the atypical agents risperidone and olanzapine, as they cause significant motor deterioration through striatal D2 receptor blockade. 1, 2, 7
Aripiprazole's partial D2 agonist properties do not protect against motor worsening in PD patients, contrary to what might be theoretically expected. 3
Black box warning applies to all antipsychotics: Increased mortality risk in elderly patients with dementia-related psychosis. 2
Common Pitfalls to Avoid
Do not assume that newer atypical antipsychotics like aripiprazole are safe in PD simply because they are "atypical"—only the three specifically recommended agents (pimavanserin, quetiapine, clozapine) have acceptable motor tolerability profiles. 1, 2
Do not continue aripiprazole if a patient is already taking it—switch to an appropriate alternative using the algorithm above. 3
Do not use aripiprazole even at very low doses, as motor worsening occurred in clinical trials starting at just 1 mg/day. 3