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Phase III Trial of Drug to Treat Psychosis in Parkinson Disease

Summary and Comment |
December 2, 2013

Phase III Trial of Drug to Treat Psychosis in Parkinson Disease

  1. Michael S. Okun, MD

Will pimavanserin be the next big drug to address hallucinations in PD?

  1. Michael S. Okun, MD

To assess the safety and efficacy of an investigational drug, pimavanserin, in treating Parkinson disease (PD) psychosis, researchers conducted a phase III, double-blind, manufacturer-funded study. Pimavanserin is a novel selective serotonin 5-HT2A inverse agonist. The researchers randomized 199 patients to placebo or pimavanserin (40 mg daily) for 6 weeks. There was a built in 2-week nonpharmacologic lead-in phase that was designed to combat a potential placebo response. The primary outcome was the Parkinson's disease adapted scale for assessment of positive symptoms (SAPS-PD).

The analysis included 95 pimavanserin recipients and 90 placebo recipients. The pimavanserin group had a 5.79-point improvement in the SAPS-PD versus only a 2.73-point improvement in the placebo group, a significant difference. Ten patients in the study group versus two in the placebo group discontinued the study medication. No worsening of PD motor function was reported.

Comment

Psychosis is common in Parkinson disease as a result of the dopaminergic drugs used to treat the motor symptoms. Thus, there is a difficult balancing act between improving motor function and psychosis. Better drugs are needed critically to address hallucinations and psychosis in these. Typically, neurologists prescribe quetiapine or clozapine instead of the classical dopamine-blocking drugs (e.g., haloperidol, olanzapine) to treat psychosis associated with PD. Classical dopamine-blocking drugs tend to worsen motor symptoms. Preservation of motor function is a big advantage favoring pimavanserin, which acts at the serotonin receptor and not the dopamine receptor. Additionally, the safety profile of pimavanserin was reported as highly favorable in this study. The hope is that pimavanserin will find a niche between quetiapine and clozapine as a viable alternative for select patients with PD. In severe psychosis cases, some might consider adding pimavanserin to seroquel or clozaril to improve treatment of difficult-to-control hallucinations and psychosis — an issue not addressed by this study. With Lewy body dementia, which also was not studied, hallucinations (especially visual), commonly occur, not related to dopamine agonist treatment. These patients are exquisitely sensitive to antipsychotics, and the current preferred treatment is acetylcholinesterase inhibitors. Whether this new drug is effective in this setting would be interesting to see. Psychosis drugs not uncommonly fail to live up to expectations. Therefore, careful monitoring of pimavanserin's roll-out will be important, as will documenting specific PD profiles associated with the drugs failures and successes.

  • Disclosures for Michael S. Okun, MD at time of publication Grant / research support NIH; National Parkinson Foundation; Michael J. Fox Foundation Editorial boards Parkinsonism and Related Disorders; Tremor and Hyperkinetic Disorders Leadership positions in professional societies National Parkinson Foundation (Medical Director and Ask the Doctor Director); Tourette Syndrome Association (Medical Advisory Board)

Citation(s):

Reader Comments (2)

George B Howell, MD Physician, Family Medicine/General Practice, Private Clinic

I hope it continues to be effective.

minh LE Physician, Neurology, department of neurology - movement disorders unit, University Medical Center

very useful update

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