Parkinson’s Psychosis and Treatment

Parkinson’s Disease (PD) is a progressive neurodegenerative motor disorder with the classic triad of symptoms of bradykinesia, resting tremor, and rigidity. The prevalence for PD increases with individuals ≥ 80 years with the incidence estimated at 1903 per 100,000 population.1,2

At the cellular level, there is an associated imbalance of dopamine to acetylcholine contributing to the nigrostriatal tracks needing exogenous dopaminergic enhancement. Traditionally, carbidopa/levodopa is used to increase dopamine in the CNS; however, excessive dopamine can cause significant psychosis.  Furthermore, psychosis is not just an adverse effect but, The National Institute of Neurological Disorders and Stroke and National Institute of Mental Health combined workgroup used the term “Parkinson’s Disease psychosis” (PDP) to describe the various psychotic symptoms that present as a continuum of PD progression.3

Parkinson’s Disease Psychosis (PDP) can significantly impact quality of life, be a predictor of mortality and is quite common with a prevalence of 25-30%.4,5 Moreover, treatment for PDP should be multifaceted with behavioral interventions being first line especially with limited medication options. While antipsychotics are the mainstay treatment for PDP, recall that their mechanism of action is blockade of the dopaminergic receptors (D2) and therefore may worsen the motor symptoms of the Parkinson’s disease.4,5 Additionally, in a Skilled Nursing Facility, antipsychotics are tightly regulated by CMS guidelines and require gradual dose reductions (GDR) unless clinically contraindicated. 

Interestingly, according to CMS Appendix PP: “Residents with specific, enduring, progressive, or terminal conditions such as chronic depression, Parkinson’s disease psychosis, or recurrent seizures may need specific types of psychotropic medications or other medications which affect brain activity indefinitely.”Currently available antipsychotic agents commonly being used to treat PDPinclude clozapine, quetiapine (least dopaminergic), olanzapine  and more recently, pimavanserin.1,3  The only on-label FDA approved antipsychotic for the treatment of PDP is pimavanserin, thus, other antipsychotics because they are being prescribed off-label generally fall under the CMS gradual dose reduction guidelines.  Prescribers who believe that GDR of other antipsychotics is contraindicated should document the reasons why in the resident’s chart to help ensure the resident is receiving appropriate therapy and the facility is not subjected to regulatory sanctions.

A recent systematic review by Wilby et al.5 assessed data from 16 studies that explored the antipsychotic treatment options for PDP.2,5 In this systematic review eleven studies compared active drugs to placebo and five studies compared clozapine to another active drug.2,5 The conclusion of this systematic review showed the placebo-controlled trials demonstrated benefit for clozapine and pimavanserin for the treatment of PDP, with no definitive benefits noted for either quetiapine or olanzapine. 2,5

There have been several studies that suggest the following when considering treatment of PDP a stepwise approach should be utilized2,4

  1. Assess the severity of psychotic symptoms and whether an intervention is required (include treating secondary causes that may have triggered acute psychosis); 

  2. Thoroughly review patient’s medication regimen and discontinue any nonessential non-PD medications; 

  3. Modify and gradually discontinue PD medications as tolerated that are no longer effective;

  4. Lastly, simplify and reduce PD medications to the lowest tolerable dose without exacerbating motor symptoms.  If this does not improve psychosis, then consider adding a specific antipsychotic drug.2,4

Optimizing medication therapy for Parkinson’s Disease and the associated adverse effects involves careful drug selection and dose titration to enhance quality of life. Keep the therapy patient-centered and advocate for the best medication option for your patient, whether it is a second-generation antipsychotic or pimavanserin, if Parkinson’s Disease psychosis occurs, and remember that the guidance to surveyors (Appendix PP) suggests that long-term treatment is needed. 


  1. Pringsheim, T., Jette, N., Frolkis, A. and Steeves, T.D. (2014), The prevalence of Parkinson's disease: A systematic review and meta‐analysis. Mov Disord., 29: 1583-1590.
  2. Tampi RR, Tampi DJ, Young JJ, Balachandran S, Hoq RA, Manikkara G. Evidence for using pimavanserin for the treatment of Parkinson's disease psychosis. World J Psychiatry. 2019 Jun 10;9(3):47-54. doi: 10.5498/wjp.v9.i3.47. PMID: 31211112; PMCID: PMC6560499.
  3. Ravina B, Marder K, Fernandez HH, Friedman JH, McDonald W, Murphy D, Aarsland D, Babcock D, Cummings J, Endicott J, Factor S, Galpern W, Lees A, Marsh L, Stacy M, Gwinn-Hardy K, Voon V, Goetz C. Diagnostic criteria for psychosis in Parkinson's disease: report of an NINDS, NIMH work group. Mov Disord. 2007 Jun 15;22(8):1061-8. doi: 10.1002/mds.21382. PMID: 17266092.
  4. Ffytche DH, Creese B, Politis M, Chaudhuri KR, Weintraub D, Ballard C, Aarsland D. The psychosis spectrum in Parkinson disease. Nat Rev Neurol. 2017 Feb;13(2):81-95. doi: 10.1038/nrneurol.2016.200. Epub 2017 Jan 20. PMID: 28106066; PMCID: PMC5656278.
  5. Wilby KJ, Johnson EG, Johnson HE, Ensom MHH. Evidence-Based Review of Pharmacotherapy Used for Parkinson's Disease Psychosis. Ann Pharmacother. 2017 Aug;51(8):682-695. doi: 10.1177/1060028017703992. Epub 2017 Apr 6. PMID: 28385039.
  6. CMS Appendix PP.  page 492; accessed 5/1/2021
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Comments on "Parkinson’s Psychosis and Treatment"

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Tracy Greene Mintz - Sunday, July 04, 2021

Really interesting, Janice. SNF residents are frequently seen by the IDT only as their most troubling symptom, which is often behavior. By giving context to these psychotic symptoms, we help see, and thus treat, the whole person.

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