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Treating Psychosis That Can Accompany Parkinson's Disease

By Jennifer Anderson

Although treatment options are limited, physicians must learn to recognize and effectively treat Parkinson's psychosis.

A new medication may soon be available to treat the hallucinations and delusions that often accompany Parkinson's disease. "It shows promise in improving the hallucinations without worsening the motor functions," says Jennifer G. Goldman, MD, an associate professor of neurology at Rush University Medical Center in Chicago.

She explained that, to date, good medications for treating Parkinson's psychosis have been unavailable. "It would be very exciting to have another agent available to use," she says.

Parkinson's Psychosis
People who have Parkinson's disease may develop psychosis, possibly as a result of the medications used to treat the movement disorders but also possibly related to the disease itself.
These misperceptions can range from illusions, such as a chair looking like a dog, to false beliefs, perhaps of an unfaithful spouse or an imaginary person living in the house, Goldman explains.

The hallucinations are primarily visual—one of the many differences between psychosis symptoms in Parkinson's and those in schizophrenia. With schizophrenia, people might have delusions of grandeur, believing they have unreal abilities, or they might hear voice commands. With Parkinson's psychosis, Goldman explains, auditory hallucinations are infrequent and if they arise, generally are confined to background noise, such as children or music playing.

Why Parkinson's Patients Experience Hallucinations
Most people who develop Parkinson's disease do so in their early 60s, Goldman says, estimating that 1% to 2% of adults acquire the disease. Studies show that about 1 million people in the United States have Parkinson's disease, which equates to approximately 360 people per million.

For about one-half of those people, psychosis will manifest itself over time, Goldman says, adding that it's unclear exactly why people with Parkinson's experience psychosis. One possibility is the medications used to treat the disease's motor disorders. The goal of those medications is to increase the levels of dopamine, a chemical messenger that helps the nerve cells in the brain transmit messages. With Parkinson's disease, dopamine is depleted. But too much dopamine can stimulate areas of the brain that could provoke delusions and hallucinations, she says.

The cognitive difficulties that can accompany Parkinson's disease are another possible trigger for the psychosis, as are the associated sleep difficulties, Goldman says. "Often if the sleep/wake cycle is disrupted, or you're drowsy during the day, you can be more susceptible to hallucinations," she says.

Changes in the visual system resulting from Parkinson's disease also may lead to hallucinations, according to Goldman. In Parkinson's disease, the loss of dopamine in a part of the eye can cause visual difficulties and possibly hallucinations. "If you're not seeing things properly, the brain could be more likely to misinterpret what you're seeing," she says.

It's also possible that the underlying disease is causing the hallucinations, and the medications are making it worse, says Rajesh Pahwa, MD, a neurologist with the University of Kansas Medical Center. "It's challenging to determine whether it's because of the medications or the disease," Pahwa says. 

Treating Parkinson's psychosis has become challenging, and Pahwa says it generally is not treated unless it is interfering with a patient's quality of life.

Pahwa presents a scenario to illustrate the considerations clinicians face in treatment determinations: "Right now we would say, 'OK, you are seeing a rat running across room. Does it bother you?' If they say, 'Oh, that rat, it comes and tries to bite me,' then we might try to cut back on some medications, which could make the Parkinson's worse. If it doesn't [bother the patient], we may stay on a lower dose for a while. If it comes back, we will try medications for the psychosis."

Two common medications for treating Parkinson's psychosis are actually approved for treating schizophrenia. The schizophrenia medications used for Parkinson's psychosis, quetiapine and clozapine, are not ideal, "but we use them because we have to treat the psychosis," Pahwa says.

He explains that the medications alleviate the hallucinations, but they do so partly by blocking dopamine, and this can worsen any improvements achieved in a patient's movement. In older Parkinson's patients with dementia, the schizophrenia medications also can increase the risk of mortality.

Another option is Exelon, or rivastigmine tartrate, a medication that has been approved for Parkinson's dementia but not for Parkinson's psychosis. Studies suggest that rivastigmine may help psychosis. "It's an off-label use, but we don't have many options," Pahwa says.

Pimavanserin could be approved as early as next year, says Pahwa, who adds that he is a consultant for Acadia Pharmaceuticals, the company that manufacturers pimavanserin. Unlike the schizophrenia medications, pimavanserin uses a different mechanism to work on serotonin levels in the brain. Studies to date on pimavanserin have shown a clean profile with few side effects, he says. 

No medication works for everyone, Pahwa says. He estimates that pimavanserin improves Parkinson's psychosis by 30% to 40% and also appears to help people sleep better at night. "In studies with pimavanserin, the psychosis is greatly reduced," he says, "but we still need better medications."

Caregiver Burden
Patients may not volunteer to their physicians or caregivers that they are having hallucinations, Goldman says. "There is a lot of stigma," she notes, adding, "I think people can be embarrassed, afraid of the repercussions of sharing psychosis. Physicians don't always ask about it either. I think it's a big problem."

She explains that while some patients are aware that what they are seeing is a hallucination, others who may not be as cognitively intact might have trouble differentiating between what is real and what is imaginary.

Over time, psychosis can worsen, she says. "We do know there are patients who might start out with mild illusions and misperceptions, or even benign hallucinations, that progress to ones that can be more frightening."

As the psychosis intensifies, so can caregiver burden and stress, Goldman says. "It can have a profound impact on the patient's and caregiver's quality of life and is one of the leading reasons patients end up in nursing homes," she says. And of course, a move to a nursing home can then exacerbate the financial burden of patient care.

"It's a huge problem," Goldman says of Parkinson's psychosis. "Treating things like dementia, cognitive impairment, and psychosis that sometimes accompany the disease are unmet needs."

— Jennifer Anderson is a freelance health and science writer based in Falls Church, Virginia.