Drug could diminish psychotic symptoms associated with Parkinson’s disease

by Bruce Sylvester – An investigative drug could offer the first safe and effective treatment for psychotic symptoms that affect about half of people with Parkinson’s disease, researchers reported in the Oct. 31, 2013 issue of the Lancet

The new agent, pimavanserin, blocks serotonin 5-HT2A receptors in the neocortex associated with visual hallucinations and delusions.

“Psychosis is a major driving factor for people with Parkinson’s disease being admitted to nursing homes and substantially increases the risk of dying. But no safe and effective drug therapies exist”, said lead investigator Professor Clive Ballard of King’s College London, UK. “Currently, the only treatment options are dopamine antagonist antipsychotic drugs such as clozapine and quetiapine which worsen motor symptoms, speed up cognitive decline, increase the risk of stroke, and can be life-threatening even with short-term use.”*

The investigators enrolled 199 subjects with Parkinson’s disease psychosis, aged 40 years or older, from 54 centers across the USA and Canada. The subjects were randomized to 40mg of pimavanserin orally once daily or matching placebo for 6 weeks.

The researchers used a nine-item Parkinson’s disease-adapted scale (SAPS-PD) to evaluate for positive symptoms of psychosis at the start of the study, and at regular intervals up to day 43.

They employed a brief run-in phase of psychosocial interaction to reduce the common placebo effect noted in Parkinson’s disease clinical trials as treatment starts.

After 43 days, patients taking pimavanserin had achieved significant improvement in SADS-PD score (psychotic symptoms) compared with those given placebo, 37% improvement vs 14%. Night-time sleep, daytime wakefulness, and caregiver burden also improved, compared with placebo.

There was no deterioration in motor symptoms among pimavanserin-treated subjects.

Professor Ballard added, “The clinical benefits of pimavanserin were seen by patients, those caring for them, and independent blinded raters alike.”*

Pimavanserin side-effects were mild-to-moderate, and similar toplacebo.  Most common were urinary tract infections (12% placebo vs 14% pimavanserin) and falls (9% vs 11%). Ten patients discontinued  pimavanserin due to an adverse event compared to four in the placebo group.

The authors concluded that, based on the study results, pimavanserin has the potential to be used to treat psychotic symptoms common in Alzheimer’s and other dementias.  Writing in a linked Comment, Susan Fox an Associate Professor of Neurology at the University of Toronto in Canada says, “Further studies will be needed to determine relative efficacy of pimavanserin and clozapine or quetiapine.  Overall, the study opens up a new therapeutic avenue in treatment of Parkinson’s disease psychosis. With a potentially improved safety profile, pimavanserin might be useful for treatment of patients with Parkinson’s disease and mild symptoms of psychosis and help prevent progression to more bothersome symptoms as well as targeting psychosis in other disorders such as Alzheimer’s disease.”