Drug may help Parkinson's disease psychosis

“New drug to relieve Parkinson’s psychosis: Breakthrough could offer better quality of life for thousands who suffer hallucinations,” reports the Mail Online.

Parkinson’s disease is a progressive neurological condition, caused by loss of brain cells that produce a chemical called dopamine. One of the most distressing symptoms of Parkinson’s is psychosis where people have hallucinations and delusions (irrational beliefs).

About half of people with Parkinson’s disease will have psychosis at some time.

Many common antipsychotic drugs target the dopamine system, and if given to patients with Parkinson’s can make the physical symptoms of the condition, such as tremor, worse.

This news is based on a study into a new antipsychotic drug called pimavanserin, which targets a different signalling system (the serotonin system).

It found that psychotic symptom scores in people with Parkinson’s improved significantly when given pimavanserin compared to placebo ("dummy treatment"). At the end of the six-week study, people who received pimavanserin had an average change in score equivalent to a 37% improvement relative to the start of the study, whereas people who received placebo had a 14% improvement.

The size of the improvement in symptoms is likely to translate into a clinical benefit. The drug was well tolerated with no significant safety concerns or worsening of motor function.

Further investigation will now be required to ensure that pimavanserin is safe and the response is maintained if pimavanserin is taken for more than six weeks.

Where did the story come from?

The study was carried out by researchers from the Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas; Parkinson’s Disease and Movement Disorders Center of Boca Raton, Florida; ACADIA Pharmaceuticals; the Barrow Neurology Institute, Phoenix; and King’s College London. It was funded by ACADIA Pharmaceuticals.

The study was published in the peer-reviewed medical journal The Lancet.

ACADIA Pharmaceuticals manufacture pimavanserin and some of the researchers involved in the study had or are working for that company; a potential conflict of interest that was made clear in the study.

The story was well covered by the Mail Online.

What kind of research was this?

This was a randomised controlled trial (RCT). It aimed to assess the safety and efficacy of pimavanserin, a new drug for Parkinson’s disease psychosis.

An RCT is the ideal study design for assessing safety and efficacy of a new drug.

What did the research involve?

The researchers enrolled 199 adults aged 40 years or older who had Parkinson’s disease psychosis.

Participants could continue to receive antiparkinsonian drugs or have deep brain stimulation throughout the study, but no antipsychotic drugs were allowed.

All participants entered a two-week lead in phase. During this phase patients received brief psychosocial therapy, consisting of daily social interactions between the person with Parkinson’s disease psychosis and their caregiver, and no drugs. The researchers report that this was to limit the "placebo response" during the trial: the very fact that people know they are taking part in a clinical trial can lead to an improvement in symptoms, so the researchers used a lead-in phase to try and cause any placebo response to take place before the participants started the trial of pimavanserin.

The participants were then randomly allocated to receive 40mg pimavanserin or placebo for six weeks.

The researchers looked to see if there was an improvement in psychotic symptoms. Psychotic symptoms were assessed and scored by an independent rater, who didn’t know whether the person was taking pimavanserin or placebo (blinded). The scoring was based on a validated scale called the Parkinson’s disease-adapted scale for assessment of positive symptoms (SAPS-PD).

Scoring was carried out at the start of the study (after the lead-in phase) and then on days 15, 29 and 43. The researchers analysed the improvement in all patients who had received at least one dose of either placebo or pimavanserin and whose psychotic symptoms had been assessed at the start of the study and at least once during follow-up. The researchers also looked at improvements in other symptom scale scores, caregiver burden and sleep.

The researchers also monitored adverse reactions (side-effects) in all patients who received at least one dose of either placebo or pimavanserin.

What were the basic results?

Psychotic symptom scores improved significantly more in people who received pimavanserin. At the end of the study (day 43), people who received pimavanserin had an average change in SAPS-PD score equivalent to a 37% improvement relative to the start of the study, whereas people who received placebo had a 14% improvement. The treatment change between groups was 3.06 points on this scale, which has nine items, and was reported as clinically meaningful as well as statistically significant.

People receiving pimavanserin also had significantly greater improvements in other symptom scale scores, and improvements in night-time sleep and daytime wakefulness compared to people receiving placebo. Caregivers of people receiving pimavanserin also reported a reduction in burden compared to caregivers of people receiving placebo.

Eleven participants in the pimavanserin and four people in the placebo group had a serious adverse event. Ten people in the pimavanserin group discontinued the drug because of adverse reaction (four due to a psychotic disorder or hallucination within 10 days of the start of the study drug), and two people in the placebo group also discontinued.

It is uncertain whether the adverse effects were related to the drug or just occurred as part of the natural progression of the condition.

The researchers said that “overall, pimavanserin was well tolerated with no significant safety concerns or worsening of motor function.”

How did the researchers interpret the results?

The researchers concluded that, “pimavanserin may benefit patients with Parkinson’s disease psychosis for whom few other treatment options exist”.

Conclusion

This well-designed randomised controlled trial has found that pimavanserin is effective in improving the symptoms of psychosis in patients with Parkinson’s disease psychosis. The size of the improvement in symptoms is likely to translate into a clinical benefit. The drug was well tolerated with no significant safety concerns or worsening of motor function.