Key Facts

  • Psychosis occurs in PD due to a combination of cognitive decline/dementia< and medication< effects.
  • Check for infection, vitamin B12, folate, TSH levels.
  • Pimavanserin, clozapine and quetiapine can be used for treatment, but monitoring is necessary.
  • Treating psychosis may reveal underlying dementia<.

Clinical Best Practices

  • Rule out other causes of dementia<.
  • The best evidence for psychosis treatment efficacy is with pimavanserin.

Psychosis in PD is very common and may also occur in the setting of infection. Psychosis has been one of the most common causes of hospitalization of PD patients and may be secondary to PD medications.

Common Causes


  • No clear diagnostic criteria
  • Illusions–misinterpretation of stimulus (chair is my dead dog, etc) are considered benign but should be monitored
  • Hallucinations–visual, auditory or sensory without stimulus;
  • Delusions–fixed ideas without any basis in reality (paranoid, delusions of infidelity, Capgras syndromei, etc)

Barriers to Diagnosis

  • Patient or family reluctance to disclose–stigma or lack of recognition that this is related to PD
  • Failure to inquire

Treatment Options

  • Check for infection, vitamin B12, folate, TSH levels
  • Stop sedatives and analgesia
  • Consider the possibility of a psychotic depression
  • Prescribe pimavanserin
  • Prescribe quetiapine
  • Prescribe clozapine

Withdraw medications in this order: anticholinergic medications>MAOBinhibitors>dopamine agonists>COMTinhibitors>minimize levodopa dose

Important Caveats to Therapy

  • Reducing PD medications may result in increased motor< impairment.
  • Treating psychosis may reveal underlying dementia<–caution families to anticipate this possibility.
  • Clozapine requires monitoring CBC and neutrophil count according to your state/province/country.
  • Clozapine and quetiapine can result in prolonged QT syndrome–do baseline ECG.
  • Clozapine and quetiapine may cause metabolic syndrome–caution patients and monitor.
  • Clozapine and quetiapine can cause orthostatic hypotension<–monitor orthostatic hypotension.
  • Quetiapine has conflicting evidence and may not improve psychosis at sufficient doses without causing sedation.

Miyasaki JM, Shannon K, Voon V, et al; Quality Standards Subcommittee of the American Academy of Neurology. Practice Parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006;66(7):996-1002.