Parkinson's disease psychosis

Characteristics

• >50% of Parkinson’s patients develop psychosis at some point, up to 75% of patients with Parkinson’s disease dementia are affected by psychosis, (Cummings et al, 2014) including:
  • illusions – misperceptions of real stimuli, such as mistaking a pillow for an animal; pareidolia refers to an illusion of seeing faces in otherwise formless visual stimuli, like clouds or treebark (Ffytche et al, 2017)
  • hallucinations – including visual hallucinations (animals, objects, or figures), passage hallucinations (a vague object passing through the peripheral visual field), and extracampine or presence hallucinations (feeling someone is present) (Ffytche et al, 2017)
    • earlier in disease course, insight is typically preserved (hallucinations with preserved insight may be referred to as hallucinosis) (Ffytche et al, 2017)
    • later, insight may be lost and hallucinations may expand into other non-visual sensory domains. (Ffytche et al, 2017)
  • delusions (false beliefs) is usually later in disease course as insight is lost; themes include persecution, jealousy, grandiosity, guilt, reference, theft, misidentification syndromes (Capgras, reduplicative paramnesia) (Ffytche et al, 2017)

Treatment

• Reduction of dopaminergic therapy (Cummings et al, 2014)
• Antipsychotics – though often poorly tolerated due to neuroleptic sensitivity (Cummings et al, 2014)
  • Quetiapine is better tolerated but not efficacious (Cummings et al, 2014)
  • Clozapine improves psychosis without worsened motor symptoms (potentially through blockade of 5-HT2A receptor), though requires weekly blood draws for the first 6 months due to risk of agranulocytosis and has high side-effect profile
  • Pimavanserin (selective 5-HT2A inverse agonist, no DA activity) improves psychosis without worsened motor symptoms, sedation, or drowsiness; it has a small QT interval increase
• Cholinergic medication (in patients with comorbid cognitive impairment)
  • Rivastigmine found to reduce NPI score (Ffytche et al, 2017)
• Electroconvulsive therapy found to be helpful in small case series of medically refractory PD psychosis patients with sustained improvement up to 30 weeks (Ueda, Koyama, and Okubo, 2010)

References

Cummings, J. et al. Pimavanserin for patients with Parkinson’s disease psychosis: a randomised, placebo-controlled phase 3 trial. Lancet Lond. Engl. 383, 533–540 (2014). https://pubmed.ncbi.nlm.nih.gov/24183563/

Ffytche, D. H. et al. The psychosis spectrum in Parkinson disease. Nat. Rev. Neurol. 13, 81–95 (2017). https://pubmed.ncbi.nlm.nih.gov/28106066/

Ueda, S., Koyama, K. & Okubo, Y. Marked improvement of psychotic symptoms after electroconvulsive therapy in Parkinson disease. J. ECT 26, 111–115 (2010). https://pubmed.ncbi.nlm.nih.gov/20386461/