Ask the MD: Parkinson’s Disease Psychosis

By Rachel Dolhun, MD

Parkinson’s disease (PD) psychosis has been in the news as pimavanserin (Nuplazid) — a novel medication to treat this non-motor symptom — nears possible Food and Drug Administration approval. (A final decision will be made no later than May 1, 2016.) Pimavanserin would be the first drug indicated for PD psychosis and could be 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

Hallucinations and delusions occur most often in those with Parkinson’s. 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.

Pimavanserin Represents a Potential New Therapy for Psychosis
The approval of pimavanserin would potentially expand the somewhat limited treatment options for psychosis in Parkinson’s. Pimavanserin 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 might 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.

If pimavanserin is approved, it’s important to remember that (like every medication) it can have side effects and it 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 always requires input from every person on the care team: patient, caregiver, family members and physician.

about pimavanserin.

 

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