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Efficacy and Safety of Analgesic Treatment for Depression in People with Advanced Dementia: Randomised, Multicentre, Double-Blind, Placebo-Controlled Trial (DEP.PAIN.DEM)
BACKGROUND: Chronic pain and depression often co-occur, and pain may exacerbate depression in people with dementia. OBJECTIVE: The objective of this study was to assess the efficacy and safety of analgesic treatment for depression in nursing home patients with advanced dementia and clinically signif...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999156/ https://www.ncbi.nlm.nih.gov/pubmed/29725986 http://dx.doi.org/10.1007/s40266-018-0546-2 |
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author | Erdal, Ane Flo, Elisabeth Aarsland, Dag Ballard, Clive Slettebo, Dagrun D. Husebo, Bettina S. |
author_facet | Erdal, Ane Flo, Elisabeth Aarsland, Dag Ballard, Clive Slettebo, Dagrun D. Husebo, Bettina S. |
author_sort | Erdal, Ane |
collection | PubMed |
description | BACKGROUND: Chronic pain and depression often co-occur, and pain may exacerbate depression in people with dementia. OBJECTIVE: The objective of this study was to assess the efficacy and safety of analgesic treatment for depression in nursing home patients with advanced dementia and clinically significant depressive symptoms. METHODS: We conducted a multicentre, parallel-group, double-blind, placebo-controlled trial in 47 nursing homes, including 162 nursing home patients aged ≥ 60 years with dementia (Mini-Mental State Examination ≤ 20) and depression (Cornell Scale for Depression in Dementia ≥ 8). Patients were randomised to receive active analgesic treatment (paracetamol or buprenorphine transdermal system) or identical placebo for 13 weeks. The main outcome measure was the change in depression (Cornell Scale for Depression in Dementia) from baseline to 13 weeks, assessed using linear mixed models with fixed effects for time, intervention and their interaction in the models. Secondary outcomes were to assess whether any change in depression was secondary to change in pain (Mobilisation-Observation-Behaviour-Intensity-Dementia-2 Pain Scale) and adverse events. RESULTS: The mean depression change was − 0.66 (95% confidence interval − 2.27 to 0.94) in the active group (n = 80) and − 3.30 (− 4.68 to −1.92) in the placebo group (n = 82). The estimated treatment effect was 2.64 (0.55–4.72, p = 0.013), indicating that analgesic treatment had no effect on depressive symptoms from baseline to 13 weeks while placebo appeared to ameliorate depressive symptoms. There was no significant reduction in pain in the active treatment group (paracetamol and buprenorphine combined) vs. placebo; however, a subgroup analysis demonstrated a significant reduction in pain for paracetamol vs. placebo [by − 1.11 (− 2.16 to − 0.06, p = 0.037)] from week 6 to 13 without a change in depression. Buprenorphine did not have significant effects on depression [3.04 (− 0.11 to 6.19), p = 0.059] or pain [0.47 (− 0.77 to 1.71), p = 0.456] from 0 to 13 weeks. Thirty-five patients were withdrawn from the study because of adverse reactions, deterioration or death: 25 (31.3%) during active treatment [23 (52.3%) who received buprenorphine], and ten (12.2%) in the placebo group. The most frequently occurring adverse events were psychiatric (17 adverse reactions) and neurological (14 adverse reactions). CONCLUSION: Analgesic treatment did not reduce depression while placebo appeared to improve depressive symptoms significantly by comparison, possibly owing to the adverse effects of active buprenorphine. The risk of adverse events warrants caution when prescribing buprenorphine for people with advanced dementia. TRIAL REGISTRATION: ClinicalTrials.gov NCT02267057 (registered 7 July, 2014) and Norwegian Medicines Agency EudraCT 2013-002226-23. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40266-018-0546-2) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5999156 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-59991562018-06-28 Efficacy and Safety of Analgesic Treatment for Depression in People with Advanced Dementia: Randomised, Multicentre, Double-Blind, Placebo-Controlled Trial (DEP.PAIN.DEM) Erdal, Ane Flo, Elisabeth Aarsland, Dag Ballard, Clive Slettebo, Dagrun D. Husebo, Bettina S. Drugs Aging Original Research Article BACKGROUND: Chronic pain and depression often co-occur, and pain may exacerbate depression in people with dementia. OBJECTIVE: The objective of this study was to assess the efficacy and safety of analgesic treatment for depression in nursing home patients with advanced dementia and clinically significant depressive symptoms. METHODS: We conducted a multicentre, parallel-group, double-blind, placebo-controlled trial in 47 nursing homes, including 162 nursing home patients aged ≥ 60 years with dementia (Mini-Mental State Examination ≤ 20) and depression (Cornell Scale for Depression in Dementia ≥ 8). Patients were randomised to receive active analgesic treatment (paracetamol or buprenorphine transdermal system) or identical placebo for 13 weeks. The main outcome measure was the change in depression (Cornell Scale for Depression in Dementia) from baseline to 13 weeks, assessed using linear mixed models with fixed effects for time, intervention and their interaction in the models. Secondary outcomes were to assess whether any change in depression was secondary to change in pain (Mobilisation-Observation-Behaviour-Intensity-Dementia-2 Pain Scale) and adverse events. RESULTS: The mean depression change was − 0.66 (95% confidence interval − 2.27 to 0.94) in the active group (n = 80) and − 3.30 (− 4.68 to −1.92) in the placebo group (n = 82). The estimated treatment effect was 2.64 (0.55–4.72, p = 0.013), indicating that analgesic treatment had no effect on depressive symptoms from baseline to 13 weeks while placebo appeared to ameliorate depressive symptoms. There was no significant reduction in pain in the active treatment group (paracetamol and buprenorphine combined) vs. placebo; however, a subgroup analysis demonstrated a significant reduction in pain for paracetamol vs. placebo [by − 1.11 (− 2.16 to − 0.06, p = 0.037)] from week 6 to 13 without a change in depression. Buprenorphine did not have significant effects on depression [3.04 (− 0.11 to 6.19), p = 0.059] or pain [0.47 (− 0.77 to 1.71), p = 0.456] from 0 to 13 weeks. Thirty-five patients were withdrawn from the study because of adverse reactions, deterioration or death: 25 (31.3%) during active treatment [23 (52.3%) who received buprenorphine], and ten (12.2%) in the placebo group. The most frequently occurring adverse events were psychiatric (17 adverse reactions) and neurological (14 adverse reactions). CONCLUSION: Analgesic treatment did not reduce depression while placebo appeared to improve depressive symptoms significantly by comparison, possibly owing to the adverse effects of active buprenorphine. The risk of adverse events warrants caution when prescribing buprenorphine for people with advanced dementia. TRIAL REGISTRATION: ClinicalTrials.gov NCT02267057 (registered 7 July, 2014) and Norwegian Medicines Agency EudraCT 2013-002226-23. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40266-018-0546-2) contains supplementary material, which is available to authorized users. Springer International Publishing 2018-05-03 2018 /pmc/articles/PMC5999156/ /pubmed/29725986 http://dx.doi.org/10.1007/s40266-018-0546-2 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Original Research Article Erdal, Ane Flo, Elisabeth Aarsland, Dag Ballard, Clive Slettebo, Dagrun D. Husebo, Bettina S. Efficacy and Safety of Analgesic Treatment for Depression in People with Advanced Dementia: Randomised, Multicentre, Double-Blind, Placebo-Controlled Trial (DEP.PAIN.DEM) |
title | Efficacy and Safety of Analgesic Treatment for Depression in People with Advanced Dementia: Randomised, Multicentre, Double-Blind, Placebo-Controlled Trial (DEP.PAIN.DEM) |
title_full | Efficacy and Safety of Analgesic Treatment for Depression in People with Advanced Dementia: Randomised, Multicentre, Double-Blind, Placebo-Controlled Trial (DEP.PAIN.DEM) |
title_fullStr | Efficacy and Safety of Analgesic Treatment for Depression in People with Advanced Dementia: Randomised, Multicentre, Double-Blind, Placebo-Controlled Trial (DEP.PAIN.DEM) |
title_full_unstemmed | Efficacy and Safety of Analgesic Treatment for Depression in People with Advanced Dementia: Randomised, Multicentre, Double-Blind, Placebo-Controlled Trial (DEP.PAIN.DEM) |
title_short | Efficacy and Safety of Analgesic Treatment for Depression in People with Advanced Dementia: Randomised, Multicentre, Double-Blind, Placebo-Controlled Trial (DEP.PAIN.DEM) |
title_sort | efficacy and safety of analgesic treatment for depression in people with advanced dementia: randomised, multicentre, double-blind, placebo-controlled trial (dep.pain.dem) |
topic | Original Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999156/ https://www.ncbi.nlm.nih.gov/pubmed/29725986 http://dx.doi.org/10.1007/s40266-018-0546-2 |
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