Tolerability of buprenorphine transdermal system in nursing home patients with advanced dementia: a randomized, placebo-controlled trial (DEP.PAIN.DEM)
Received 29 December 2017
Accepted for publication 17 March 2018
Published 16 May 2018 Volume 2018:13 Pages 935—946
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Lucy Goodman
Peer reviewer comments 3
Editor who approved publication: Dr Richard Walker
Ane Erdal,1 Elisabeth Flo,2 Dag Aarsland,3,4 Geir Selbaek,5–7 Clive Ballard,8 Dagrun D Slettebo,1 Bettina S Husebo1,9
1Department of Global Public Health and Primary Care, Centre for Elderly and Nursing Home Medicine, University of Bergen, Bergen, Norway; 2Department of Clinical Psychology, University of Bergen, Bergen, Norway; 3Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK; 4Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway; 5Centre for Old Age Psychiatric Research, Innlandet Hospital Trust, Ottestad, Norway; 6National Advisory Unit on Aging and Health, Tønsberg, Norway; 7Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway; 8Exeter Medical School, University of Exeter, Exeter, UK; 9Municipality of Bergen, Bergen, Norway
Purpose: Buprenorphine transdermal system is increasingly prescribed in people with advanced dementia, but no clinical trial has investigated the safety and factors associated with discontinuation due to adverse events in this population.
Patients and methods: One hundred sixty-two people with advanced dementia and significant depression from 47 nursing homes were included and randomized to active analgesic treatment (acetaminophen/buprenorphine) or identical placebo for 13 weeks. In this secondary analysis, the main outcomes were time to and reasons for discontinuation of buprenorphine due to adverse events. Change in daytime activity as measured by actigraphy was a secondary outcome.
Results: Of the 44 patients who received active buprenorphine 5 μg/hour, 52.3% (n=23) discontinued treatment due to adverse events compared to 13.3% (6 of 45) in the placebo group (p<0.001). Psychiatric and neurological adverse events were the most frequently reported causes of discontinuation (69.6%, n=16). Concomitant use of antidepressants significantly increased the risk of discontinuation (HR 23.2, 95% CI: 2.95–182, p=0.003). Adjusted for age, sex, cognitive function, pain and depression at baseline, active buprenorphine was associated with 24.0 times increased risk of discontinuation (Cox model, 95% CI: 2.45–235, p=0.006). Daytime activity dropped significantly during the second day of active treatment (-21.4%, p=0.005) and decreased by 12.9% during the first week (p=0.053).
Conclusion: Active buprenorphine had significantly higher risk of discontinuation compared with placebo in people with advanced dementia and depression, mainly due to psychiatric and neurological adverse events. Daytime activity dropped significantly during the first week of treatment. Concomitant use of antidepressants further reduced the tolerability of buprenorphine.
Keywords: opioids, analgesics, dementia, drug safety, adverse drug reactions
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