Editor’s Note: January 9, 2023: Many people and families with Parkinson’s disease (PD) worry about the possibility of developing hallucinations (seeing things that aren’t there) or delusions (believing things that aren’t true). These symptoms don’t happen in everyone, and they aren’t always bothersome. But for some, they can be disruptive or frightening. When that happens, doctors may recommend medication.
In 2016, the U.S. Food and Drug Administration approved Nuplazid (pimavanserin) to treat hallucinations and delusions in people with PD. Early on, questions were raised about the drug’s safety. But new research, including this publication, suggests the drug is as safe as other medications that treat psychosis. All anti-psychosis drugs, including Nuplazid, may in general, increase the risk of death in older people who have psychosis and significant cognitive changes (dementia). But it’s unclear whether this increased risk is because of the medication or the symptoms.
All medications have possible side effects and benefits. Always work with your doctor to determine which is the best option for you or your loved one.
Parkinson's disease (PD) psychosis has been in the news since Nuplazid (pimavanserin) — a novel medication to treat this non-motor symptom — was approved by the U.S. Food and Drug Administration in April 2016. Nuplazid is the first drug indicated for PD psychosis and represents an important step in the evolution of therapies for non-motor symptoms of Parkinson's.
PD Psychosis Comes in Varied Forms
Estimates vary — maybe because symptoms are underreported — but psychosis can eventually affect more than half of people with PD. This symptom is more common in people with a longer duration (and increased severity) of disease, cognitive impairment or dementia, and older age. Other risk factors include mood, sleep and visual (e.g., need for corrective lenses, cataracts, glaucoma) disturbances. Psychosis can appear in a variety of ways, including:
• Hallucinations: seeing things that aren't there
• Delusions: holding false, typically paranoid, beliefs
• Illusions: misinterpreting things that are there
• False sense of presence: feeling that someone is nearby when no one is present
In those with Parkinson's psychosis, hallucinations and delusions occur most often. Visual hallucinations usually consist of people (e.g., small children or deceased relatives) or animals; they happen in the evening (or periods of lower stimulation) and last seconds to minutes. Delusions typically center on themes of spousal infidelity or financial concerns and — despite evidence pointing otherwise — a person cannot be convinced of their falsehood. An illusion is mistaking one object for another (i.e., thinking a garden hose is a snake).
In some cases, psychosis is mild and a person knows that these experiences are not real. In others, symptoms are more severe and can considerably disrupt the lives of the person with PD, his or her caregiver, and family. PD psychosis may even contribute to the need for an alternative living situation, such as a nursing home.
Parkinson's Disease and Drugs Can Cause Psychosis
Parkinson's psychosis can be caused by the underlying disease and/or the medications used to treat it. As the brain chemical dopamine diminishes in Parkinson's, many PD drugs work to temporarily replenish it. While the increased dopamine can lessen motor symptoms, it can also stimulate brain areas that lead to psychosis.
Management of Psychosis Requires a Stepwise Approach
When psychosis occurs, doctors first look for other medical illnesses — such as infections or electrolyte imbalances — that could be causing symptoms. If these aren't present or psychosis persists after treatment, the next step is to reduce and/or remove Parkinson's drugs. The goal of medication adjustment is to decrease psychosis without significantly worsening motor symptoms. If this cannot be done, an atypical antipsychotic agent may be added. These drugs are used for mood and thought disorders, such as schizophrenia, but they are prescribed off-label for PD psychosis. They generally work by blocking dopamine effects, though, so as they ease psychosis, they may make motor symptoms worse. Clozapine (Clozaril) is the least likely to do the latter, but low doses of quetiapine (Seroquel) are well tolerated too, so doctors typically prescribe one of these medications. Potential risks with these medications include sleepiness and, for clozapine, a decrease of infection-fighting white blood cells (which necessitates regular blood monitoring). In some situations, rivastigmine (Exelon) — which is indicated for PD dementia — is prescribed off-label for psychosis instead.
Nuplazid Is a New Treatment Option for Psychosis
The approval of Nuplazid (pimavanserin) expands the somewhat limited treatment options for psychosis in Parkinson's. This drug works on the serotonin (rather than dopamine) brain chemical system. Since this is a different mechanism than that of the presently available antipsychotic medications, it could help psychosis without aggravating motor symptoms. In short-term studies, the medication also seemed to improve nighttime sleep and daytime wakefulness while lessening the burden of psychosis on caregivers.
It's important to remember that, like all therapies, Nuplazid has potential side effects and isn't right for everyone. A person who is doing well on his or her current drug regimen doesn't necessarily have to change simply because a newer therapy comes on the market. But, for those with uncontrolled psychosis and/or intolerable side effects on current treatment, trying a different drug may be beneficial. No matter which therapy is chosen, communication about medication benefits and side effects, as well as regular assessment of the challenges psychosis poses for both the person with PD and the caregiver, must be maintained. Optimal management of each Parkinson's symptom (especially psychosis) always requires input from every person on the care team: patient, caregiver, family members and physician.
Ask the MD has been made possible through the leadership of members of our Parkinson's Disease Education Consortium in conjunction with The Albert B. Glickman Parkinson's Disease Education Program. These partners' support allows us to furnish high-quality educational content to the Parkinson's community while maintaining our commitment to allocate donor dollars to high-impact research. Editorial control of all Michael J. Fox Foundation-published content rests solely with the Foundation.