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Barriers to Treating Psychosis in Parkinsonís with Clozapine

Clozapine is widely recognized as the most effective treatment for psychosis (often experienced as hallucinations or delusions) among people with Parkinson’s disease (PD).  However, a new study finds that clozapine therapy is often removed from the PD treatment regimen because it is challenging to administer, requiring careful follow-up such as weekly blood tests.  The results were published in March in the open access journal PLoS ONE.

Many people with PD develop symptoms of psychosis several years into their diagnosis.  These can range from fleeting visual hallucinations — seeing something out of the corner of the eye that isn’t there — to more troublesome delusions, such as when the person thinks others are out to harm or steal from them.  People with PD are unable to take standard medications for psychosis because medications block dopamine, and exacerbate movement symptoms of PD.  Instead, doctors prescribe clozapine, which does not block dopamine.  Clozapine carries a FDA black box warning because it can cause a rare but dangerous drop in a person’s white blood cells, so people taking the drug must have weekly blood testing to monitor for this side effect.

At the University of Florida Center for Movement Disorders and Neurorestoration, in Gainesville, FL, researchers previously established a registry to follow people with PD at the center who were treated for psychosis with clozapine.  The registry includes information on psychotic symptoms, clozapine dose, response to the medication, stage of PD, PD symptoms and other PD medications.  For the new study, researchers led by Nawaz Hack, M.D., analyzed the registry records from 2005 to 2012 and reported on experiences of the center’s professionals in treating people with PD with clozapine.


  • Thirty-six people on the registry were included in the analysis (32 with PD, four diagnosed with parkinsonism-plus).
  • One-third of participants, while taking clozapine, experienced no symptoms of psychosis; one-third had some symptoms of psychosis and for the remainder: they either still had psychotic symptoms or the results were not recorded.
  • About 40 percent of participants continued clozapine therapy during the time period studied.
  • Of those who stopped taking the drug, the most common reason given by the patient (28 percent) was the inconvenience of weekly blood tests, even when the psychosis was resolved.
  • All participants who were placed in a nursing home (11 percent) discontinued clozapine.  Nursing home staff were concerned about the potential side effects of clozapine as well as the need for frequent blood draws.

What Does It Mean?

This study, although small, points out the practical challenges of treating PD psychosis with clozapine, which is the only treatment available for PD psychosis proven to be clinically effective in clinical trials.  Even when the medication was effective, many people stopped using it because they reported that having blood drawn frequently was uncomfortable or inconvenient, or because it required travel to the clinic that they found difficult. 

Furthermore, the difficulty of managing psychosis at home is often a reason for a person’s transfer to a nursing home, but in this study, nursing homes did not administer clozapine, for a variety of reasons.  The researchers suggest that educating nursing home doctors and staff could help make the use of clozapine more feasible in this setting, and that clinicians in general should be aware of the barriers to its use.

This study highlights an unmet gap in PD treatment. There is an urgent need for medications for psychosis in which administration is less complicated than clozapine. Such treatment may postpone time for admission to a nursing home and improve quality of life significantly.

Learn More

Do you have questions about psychosis and Parkinson's? Find answers by contacting us at (800) 457-6676 or or use our free resources below. 

View Webinar: Demystifying Hallucinations, Night Terrors and Dementia

Reference: Hack N, Fayad SM, Monari EH, Akbar U, Hardwick A, Rodriguez RL, Malaty IA, Romrell J, Shukla AAW, McFarland N, Ward HE, Okun MS (2014) An eight-year clinic experience with clozapine use in a Parkinson's disease clinic setting. PLoS ONE 9:e91545. DOI: 10.1371/journal.pone.0091545

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Source Date: Apr 22 2014