One of the leading risk factors for placing a Parkinson’s disease patient into a nursing home or long-term care facility is the onset of hallucinations and delusions, a non-motor aspect of Parkinson’s disease called Parkinson’s disease psychosis. Even though Parkinson’s disease psychosis is very common, affecting more than half of all patients over the course of their illness, caregivers are often caught off guard when their loved one starts seeing people, animals or other visions that are not there (hallucinations) or believing ideas that are not true (delusions). Certain paranoid themes are remarkably common in these patients expericneing delusions, such as beliefs that their long-wed spouse is committing adultery or fraud. It is also common for a patient to believe that something is directed toward them when it is not, such as a TV character speaking directly to them.

Until recently, clinicians did not have an FDA-approved treatment to address Parkinson’s disease psychosis. But in late April 2016, the Food and Drug Administration approved NUPLAZID (pimavanserin) to treat the hallucinations and delusions associated with Parkinson’s disease psychosis. In addition to being the first drug approved for this specific indication, NUPLAZID is the first in a new class of atypical antipsychotics, called selective serotonin inverse agonists (SSIA), that preferentially target 5-HT2A receptors, which are thought to play an important role in Parkinson’s disease psychosis.

Most importantly to those with Parkinson’s, NUPLAZID does not block dopamine receptors, and thus does not further impair motor function.  

Clinical impact

Prior to the FDA approval of NUPLAZID, the tool box to treat Parkinson’s disease psychosis was very limited. Typically, a physician would first try to adjust or reduce Parkinson’s medications, with the obvious potential to result in the worsening of motor disturbances. From a psychiatric perspective, hallucinations and delusions can be addressed through reassurance and/or cognitive behavioral therapy, though neurologists and psychiatrists also prescribed certain atypical antipsychotics like clozapine and quetiapine off-label in an effort to reduce their impact. However, there is no data to support the use of these medications to reduce hallucinations or delusions in the Parkinson’s population, and a recent study confirmed that Parkinson’s disease patients face a higher risk for mortality when on atypical antipsychotics.

The approval of NUPLAZID will have a positive impact on our ability as physicians to treat Parkinson’s patients with hallucinations and delusions. The pivotal trial data evaluated by the FDA demonstrated that Parkinson’s patients showed significantly fewer features of psychosis — hallucinations, delusions, and behavior changes — compared to those taking a placebo, as measured by the Scale for the Assessment of Positive Symptoms adapted for Parkinson’s disease (SAPS-PD) –  and accomplished this without worsening primary motor symptoms of the disease. NUPLAZID does not interfere with the motor control achieved by patients’ dopaminergic therapy because its novel mechanism of action targets target 5-HT2A (serotonin) receptors. Further, NUPLAZID can be given with Parkinson’s medications and there is no dose adjustment required for elderly patients.

Normalizing Parkinson’s disease psychosis

Clinicians have an important role to play in monitoring for hallucinations and delusions, because while psychotic symptoms in Parkinson’s disease may be considered mild with retained insight when they first occur, eventually the condition will progress. As the frequency and intensity increase, patients may become troubled, frightened or agitated.

Unfortunately, only between 10% and 20% of patients or their caregivers report the onset of such symptoms to their provider, possibly because they are embarrassed  or because they do not realize that Parkinson’s disease – a movement disorder – has non-motor symptoms.

Parkinson’s disease psychosis has tremendous caregiver burden. Providers as well as administrators in the long-term care facility should be aware that, understandably, caregivers are under stress and may feel frustrated by their ability to cope with a loved one who cannot be reasoned with when the hallucinations and delusions are particularly persistent. As family and caregivers begin to feel overwhelmed, the decision to seek long-term care placement is often made.  Once placed in a nursing home, patients are likely to remain there permanently.

If doctors explain that Parkinson’s disease is characterized by both motor and non-motor symptoms, then caregivers may feel more comfortable reporting hallucination and delusion occurrences. It is also important for doctors to ask questions during office visits that would elicit symptoms, such as “do you ever feel like your eyes are playing tricks on you?” If we are able to diagnose Parkinson’s disease psychosis earlier, before it becomes too burdensome, we may be better positioned to manage the condition. In cases where it is appropriate, NUPLAZID represents a potential treatment option that has been shown to reduce hallucinations and delusions without worsening motor symptoms for these patients.

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