Antipsychotics May Increase Death Risk in People with Parkinson’s Disease Psychosis

Antipsychotic drugs may increase the risk of death in people with Parkinson’s disease psychosis (PDP), according to a new study led by researchers from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London.

The study, published in JAMDA, found that people with PDP who were treated with antipsychotics were four times more likely to have died following three to six months of treatment than those who did not receive any antipsychotic medication. They were also more likely to experience serious health issues including cognitive decline, worsening of Parkinson’s symptoms, stroke, infections and falls.

Parkinson’s disease affects approximately 7-10 million people worldwide and is characterised by progressive loss of motor function, psychiatric symptoms and cognitive impairment. Psychosis is a common and distressing group of psychiatric symptoms affecting people with Parkinson’s, usually manifesting as hallucinations and delusions.

PDP affects more than 50 per cent of people with Parkinson’s at some point in their condition and antipsychotic drugs are often used to treat this psychosis, yet there is little evidence to support their use.

The researchers examined more than 400 people with PDP, who were taking part in a separate trial, to assess the impact of antipsychotic medications on their overall health and wellbeing. Participants were categorised into two groups – those receiving antipsychotics and those who did not take any antipsychotic medications at any time during the study.

Professor Clive Ballard from the Wolfson Centre for Age-Related Diseases at the IoPPN, King’s College London, said: ‘Our findings clearly indicate serious risks associated with antipsychotics and highlight the need for greater caution in treating psychosis in Parkinson’s disease.

Image shows pill packets.
PDP affects more than 50 per cent of people with Parkinson’s at some point in their condition and antipsychotic drugs are often used to treat this psychosis, yet there is little evidence to support their use. Image is for illustrative purposes only.

‘Antipsychotics are known to be linked to serious harm in people with Alzheimer’s Disease, and these findings show that a similar, although not identical, risk is seen in people with Parkinson’s. Our findings therefore strongly suggest that doctors, patients and family members should consider these risks very carefully when considering potential treatments for psychosis and any other behavioural symptom in people with Parkinson’s Disease, such as agitation or aggression.

‘Further research is required to develop new, better treatments for psychosis and other behavioural symptoms.’

Professor Ballard added: ‘For example, a study we published last year showed that a novel antipsychotic, pimavanserin, was effective and had far fewer side effects than traditional antipsychotics.’

About this neurology research

Source: Jack Stonebridge – King’s College London
Image Source: The image is in the public domain
Original Research: Abstract “Impact of Current Antipsychotic Medications on Comparative Mortality and Adverse Events in People With Parkinson Disease Psychosis” by Clive Ballard, MD, Stuart Isaacson, MD, Roger Mills, MD, Hilde Williams, BSc, Anne Corbett, PhD, Bruce Coate, MSc, Rajesh Pahwa, MD, Olivier Rascol, MD, and David J. Burn, MD in JAMDA. Published online July 31 2015 doi:10.1016/j.jamda.2015.06.021


Abstract

Impact of Current Antipsychotic Medications on Comparative Mortality and Adverse Events in People With Parkinson Disease Psychosis

Objectives
To establish the mortality risk and adverse events associated with the use of atypical antipsychotic medications in people with Parkinson disease psychosis (PDP) in a clinically defined trial cohort.

Design
Post hoc analysis of data from a multicenter, open-label extension study of pimavanserin comparing people taking and not taking current antipsychotics.

Setting
Primary and secondary care medical centers in the United States, Canada, Europe, and India.

Participants
A total of 459 people with PDP enrolled in the extension study. Participants were between ages 30 and 80 years, and had an established diagnosis of idiopathic Parkinson disease and moderate to severe psychosis.

Interventions
Participants were categorized into 2 groups: those receiving concomitant antipsychotic medications (“concurrent APD”) and those who did not take antipsychotic medications at any time during the study (“no APD”). Participants were receiving 40 mg pimavanserin daily in addition to concurrent antipsychotics and Parkinson disease medications.

Main Outcome Measures
Safety assessments at 2 weeks; 1, 3, 6, 9, and 12 months; and every 6 months thereafter, including evaluation of adverse events (AEs), vital signs, weight, physical examinations, 12-lead electrocardiograms, clinical laboratory tests (serum chemistry, hematology, and urinalysis), and the Unified Parkinson’s Disease Rating Scale Parts II and III (UPDRS-II+III, activities of daily living and motor impairment, respectively). Differences between participants taking and not taking current antipsychotics were evaluated using incidence rate ratios (IRRs) with 95% confidence intervals (CIs).

Results
There was significant increase in the mortality rate for participants taking concurrent antipsychotics compared with the group not taking antipsychotic medications (IRR 4.20, 95% CI 2.13–7.96). Participants who received a concurrent antipsychotic were also significantly more likely to experience overall a serious AE (IRR 2.95, 95% CI 2.02–4.24), any antipsychotic-related event (IRR 1.66, 95% CI 1.18–2.29), cognition-related events (IRR 2.70, 95% CI 1.19–5.58), infections (IRR 1.97, 95% CI 1.17–3.16), and edema (IRR 2.61, 95% CI 1.09–5.59). The risk of falls, stroke, sedation, orthostatic hypotension, and thromboembolic events was also increased in these individuals but this was not significant.

Conclusions
This study highlights a significant risk of mortality, and severe AEs in patients with Parkinson disease receiving atypical antipsychotics. This is similar to or greater than the risks seen in people with Alzheimer disease, although with a less clear-cut risk of stroke and a longer delay to increased mortality.

“Impact of Current Antipsychotic Medications on Comparative Mortality and Adverse Events in People With Parkinson Disease Psychosis” by Clive Ballard, MD, Stuart Isaacson, MD, Roger Mills, MD, Hilde Williams, BSc, Anne Corbett, PhD, Bruce Coate, MSc, Rajesh Pahwa, MD, Olivier Rascol, MD, and David J. Burn, MD in JAMDA. Published online July 31 2015 doi:10.1016/j.jamda.2015.06.021

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