Psychosis is a common problem in advancing Parkinson disease (PD). There are significant limitations of standard approaches of adjusting dopamine replacement therapies and using unconventional anti-psychotic agents such as clozapine and quetiapine. Pimavanserin is a promising addition to our therapeutic arsenal. Hawkins and Berman thoughtfully emphasize our relatively limited knowledge of pimavanserin clinical pharmacology. It was approved on the basis on 1 trial in a selected group of PD participants. Additional trials, particularly in PD dementia and Lewy body dementia subjects, and good post-marketing surveillance are needed to fully understand the utility of this agent.
How should clinicians use this agent now? Psychotic symptoms, usually visual hallucinations and illusions, are common in PD but frequently don’t require treatment. Like other PD features, psychotic symptoms should be treated when they cause disability. Many PD patients experience infrequent, non-threatening hallucinations. Some patients have preserved insight into the unreality of their hallucinations, mitigating the need for treatment. In some demented patients, even frequent hallucinations do not cause significant disability. Pimavanserin, like other new agents directed at niche markets, is expensive. As Hawkins and Berman point out, costs to patients will vary considerably. Regardless of costs to patients, the social cost remains relatively high. After some discussion, our Movement Disorders group decided to treat pimavanserin as a second line agent. We elected to initially trial low dose quetiapine in PD patients with troublesome psychotic symptoms. If unsuccessful, we try pimavanserin. Our approach may change as experience with pimavanserin accumulates.
Practicing clinicians, especially Movement Disorders specialists, can play an important role in expanding our knowledge of pimavanserin effects. The discovery of dopamine agonist related impulse control disorders, for example, began with a small case series reported by Mark Stacey. Dr. Stacey’s example is a good model for clinicians using new agents.
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