Informing Patients About Mortality Risks When Treating Drug-Induced Psychosis in Parkinson’s Disease

Informing Patients About Mortality Risks When Treating Drug-Induced Psychosis in Parkinson’s Disease

Treating Drug-Induced Psychosis in Parkinson’s DiseaseMost people associate Parkinson’s disease with motor symptoms like uncontrollable tremors, stiff or slow movement, and a blank expression. They don’t realize that the classic presentation doesn’t begin to tell the complete story, because Parkinson’s patients face another challenge in the form of non-motor symptoms like psychosis.

Parkinson’s is known for its high prevalence of psychiatric conditions, including the hallucinations and delusions caused by psychosis. Such non-motor symptoms cause significant morbidity, distress, and worse—the antipsychotics used to treat psychosis significantly increase the risk of mortality. Pharmacists must be prepared to discuss this difficult topic with Parkinson’s patients and their caregivers.

Overview of Psychosis in Parkinson’s Disease

Parkinson’s disease is the second most common neurodegenerative disease, but its prevalence increases dramatically with age. In 40- to 49-year-olds, it’s estimated to occur in 41 per 100,000 people. That number rises to 107 per 100,000 in people aged 50 to 59, jumps to 428 from age 60 to 69, and is 1087 per 100,000 in 70- to 79-year-olds.1 Most of these patients won’t be prepared for psychiatric symptoms.

At the time of diagnosis, the focus is on motor symptoms and patients are told that progression through Parkinson’s five stages is slow and gradual. If psychosis is even mentioned, they’re told it won’t develop until the fifth stage, which is the most advanced stage when patients require a wheelchair or are bedridden. While existing literature suggests that psychosis appears about 10 years after the initial diagnosis, a recent survey contradicts that data:2

  • Psychosis occurs within 4 years following diagnosis in 60 percent of patients, according to a 2015 survey of physicians.
  • More than 50 percent of all Parkinson’s patients will develop psychosis.
  • Psychosis is tightly correlated with worsening health and deteriorating quality of life.
  • Psychosis is an independent predictor of nursing home placement.
  • Nearly 88 percent experience other non-motor symptoms such as anxiety, depression, fatigue and sleep problems.

Here’s a list of the symptoms associated with Parkinson’s disease psychosis (PDP):

  • Hallucinations occur in half of PDP patients.3
  • Visual hallucinations are the most common—they occur in up to one-third of patients on chronic dopaminergic therapy.
  • Auditory hallucinations—appear in 20 percent of PDP cases.
  • Delusions occur in 33 percent of patient—they often signify more advanced disease.
  • Paranoia strikes 32 percent.
  • Lack of impulse control occurs in 33 percent.
  • One-fourth of patients become aggressive.

When psychosis is first noticed, the visual hallucinations may be simple and may not disturb the patient. In fact, the patient may not even report the hallucination because it seems like a natural event, such as seeing ants on the floor. Over time, visual hallucinations progress to become alarming and disruptive. Patients may flee their home when they believe they see an intruder or walk out of the house because they’ve seen a golfing buddy waiting for them outside. Delusions often revolve around paranoid thoughts that make the patient more distrustful, even of their loved ones who are trying to help.

Mortality Risks Associated with Treatment for Parkinson’s Psychosis

The dopaminergic medications used to treat Parkinson’s are considered to be the primary cause of psychosis, but physicians have also begun to explore multiple factors that may influence its onset, including disease severity as it may spread to the brain and a family history of dementia. After PDP is diagnosed, physicians face a general lack of effective treatment strategies, as no FDA-approved medications are currently available. In spite of black box warnings carried by atypical antipsychotics and limited evidence supporting their efficacy in PDP, they’re commonly prescribed to treat PDP.

A study published in JAMA Neurology in July 2011 found that half of patients with PDP were prescribed antipsychotic agents.4 This information came from Veterans Affairs data for 2,597 patients with Parkinson’s psychosis who were stratified by dementia status, then that data was compared to information from 6,907 patients who had dementia and psychosis, but were not diagnosed with Parkinson’s. The authors also reported that prescribing rates for individual antipsychotics changed, but that the overall number of antipsychotic prescriptions remained constant from 2002 to 2008—in spite of black box warnings placed on labels in 2005.

In addition to the well-known risks of using antipsychotics, patients with Parkinson’s psychosis face other adverse effects. Antipsychotics have the potential to worsen Parkinson’s motor symptoms. They also increase the risk of death. Parkinson’s patients are already at a 4- to 6-times greater risk of dying compared to their non-Parkinson’s counterparts matched by age, sex and race. But those who take antipsychotics are 2.35 times more likely to die within six months compared to those who don’t take antipsychotic agents, reported JAMA Neurology in May 2016.5 The study further revealed that the relative risk of death varied by drug:

  • Quetiapine fumarate carried a 2.16 times higher risk of death compared to non-treatment.
  • Risperidone users had a risk that was 2.46 times higher.
  • Olanzapine’s risk was 2.79 times higher.
  • Haloperidol increased the risk to 5.08.
  • First-generation antipsychotics collectively were associated with a 50 percent greater relative mortality risk compared to atypical antipsychotics.

Counseling for Parkinson’s Psychosis Supports Patients and Caregivers

As the disease progresses, Parkinson’s presents a significant challenge to patients and caregivers even without the presence of psychosis. Psychiatric symptoms frequently cause more distress than motor symptoms. Patients and caregivers are often at a loss. Patients don’t understand what’s happening and caregivers don’t know how to manage psychotic symptoms.

Pharmacists can help by counseling about the risks for psychiatric symptoms when they dispense Parkinson’s medications, especially dopaminergic agents or antipsychotics. It’s far better for them to be prepared for possibilities than to be anxious and worried about unexpected symptoms. Most importantly, be sure to include caregivers in counseling sessions. They must be able to identify early symptoms so they can get the patient back to the doctor as quickly as possible. Early treatment changes may improve quality of life and enable caregivers to keep their loved ones with Parkinson’s at home longer.

Pharmaceutica North America provides medications used to treat Parkinson’s disease, such as amantadine, as well as prescription drug products, bulk active pharmaceutical ingredients, and OTC supplements. Contact us today to talk about how we can support your pharmaceutical needs.

Show 5 footnotes

  1. “The Prevalence of Parkinson’s Disease: A Systematic Review and Meta-Analysis,” November 2014,
  2. “Parkinson’s Disease Psychosis: Symptoms, Management, and Economic Burden,” August 2015,
  3. “Parkinson’s Disease Psychosis (PDP): Characteristics of the PDP Patient in Clinical Practice,” June 2015,
  4. “Patterns and Trends in Antipsychotic Prescribing for Parkinson Disease Psychosis,” July 2011,
  5. “Association of Antipsychotic Use With Mortality Risk in Patients With Parkinson Disease,” May 2016,

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