CHICAGO—Transdermal buprenorphine is associated with a significant increase in harmful side effects in people with dementia, according to data described at AAIC 2018.
About half of people with dementia who are living in nursing homes have clinically significant pain. Previous research has suggested that pain often is underdiagnosed and poorly managed in people with dementia. These shortcomings affect patients’ quality of life.
Opioid-based painkillers often are second-line treatments for people with dementia, and clinicians prescribe them to approximately 40% of people with dementia who live in nursing homes. These drugs reduce pain effectively, yet current prescribing guidance does not account for the fact that people with dementia get effective pain relief from smaller doses than are commonly prescribed. In addition, people with dementia are particularly sensitive to adverse drug effects.
Clive Ballard, MD, Professor of Age-Related Diseases at the University of Exeter Medical School in the United Kingdom, and colleagues conducted a secondary analysis of a randomized, placebo-controlled trial to investigate the safety of the buprenorphine transdermal system in patients with dementia. They also analyzed the extent to which adverse events led patients to discontinue treatment with buprenorphine. The trial’s primary objective had been to examine the safety and efficacy of analgesic treatment for depression in this population.
The researchers examined 162 people with advanced dementia and significant depression from 47 Norwegian nursing homes. Participants were randomized to analgesic treatment with paracetamol, buprenorphine, or placebo for 13 weeks. The main outcomes of the investigators’ secondary analysis were time to and reasons for discontinuation of treatment due to adverse events. The secondary outcomes were change in daytime activity and intensity, as measured by actigraphy.
A total of 44 patients received 5 μg/h of active buprenorphine. Of this group, 23 (52.3%) discontinued treatment because of adverse events, compared with six (13.3%) in the placebo group. The most frequent adverse events were psychiatric and neurologic (69.6%) and included personality changes, confusion, and sedation. Concomitant use of antidepressants significantly increased the risk for discontinuation (hazard ratio, 23.2). After the researchers adjusted the data for age, sex, cognitive function, and pain at baseline, active buprenorphine was associated with a 20.9-times increased risk of discontinuation. Participants’ daytime activity decreased significantly (–21.4%) during the second day of active treatment and decreased by 12.9% during the first week.
“Pain is a symptom that can cause huge distress, and it is important that we can provide relief to people with dementia,” said Dr. Ballard. “Sadly, at the moment, we are harming people when we are trying to ease their pain. We urgently need more research in this area, and we must get this dosing right. We need to establish the best treatment pathway and examine appropriate dosing for people with dementia.”
Erdal A, Flo E, Aarsland D, et al. Efficacy and safety of analgesic treatment for depression in people with advanced dementia: randomised, multicentre, double-blind, placebo-controlled trial (DEP.PAIN.DEM). Drugs Aging. 2018;35(6):545-558.