Efficacy of Pain Treatment on Depression in Patients with Dementia. A Randomized Clinical Trial of Efficacy

Depression is common in older people and nursing home (NH) patients with dementia. Treatment with antidepressants is a clinical priority but the evidence base is sparse and studies demonstrate absence of benefit compared to placebo and increased risk of several adverse events in intervention groups. Depression is a common comorbidity amongst people with chronic pain in form of interactive relationship. Our own research demonstrated efficacy of pain treatment on agitation and aggression in patients with dementia. Secondary analyses suggest benefit of pain treatment also on depression. It is crucial to follow up these results: DEP.PAIN.DEM (Depression and Pain in Patients with Dementia), a 13-week, multicenter, parallel-group, double-blind, placebo-controlled RCT, aims to investigate the efficacy of pain treatment on depression in people with dementia. Participants (N=162) have been included from NHs in Bergen, Stavanger, Oslo, Bærum and Ålesund. Patients were eligible if they were >59 years, with probable or possible dementia (in accordance to NINCDS, ADRDA), coexisting depression (>3 weeks duration) that was assessed as needing antidepressants (CSDD>7), or despite ongoing treatment with antidepressant. Exclusion criteria were: Advanced severe medical disease with expected survival <6 months, severe psychiatric disorder, and severe aggression. Patients were randomized (1:1) to pain treatment with paracetamol or buprenorphine for 13 weeks, or identical inactive placebo. Primary and secondary outcomes were assessed at baseline, week 6, and week 13, and outcome data were measured in terms of the quality of life, behavioral symptoms including depression and agitation, daily life activities, pain, and adverse events. Inclusion and treatment has now been completed, with 162 patients included from 47 nursing homes in Rogaland, Hordaland, Møre og Romsdal, Oslo and Akershus. Processing of data, statistical analyses and work on publications is currently ongoing. The first article, which investigates the effect of analgesic treatment on depressive symptoms, titled «Efficacy and safety of analgesic treatment for depression in people with advanced dementia: randomised, multicentre, double-blind, placebo-controlled trial (DEP.PAIN.DEM)» is currently under peer review in an international journal. The second article, with the preliminary title «Tolerability of buprenorphine in people with advanced dementia: a randomised, placebo-controlled trial (DEP.PAIN.DEM)» is expected to be submitted to a journal by September 2017. The PhD thesis is expected to be submitted by October 2017, with the doctoral defense completed by March 2018. Collaboration is established between the universities of Bergen and Oslo, Stavanger Univ. Hospital; Karolinska, Stockholm; Kings College, London; and EU-COST-ActionTD1005. Joint publications between researchers at King's College London, University of Exeter, Université Clermont Auvergne and the University of Bergen are in progress, which we hope will form the basis for joint grant applications to further investigate the efficacy and safety of opioid analgesic use in people with dementia.

Depression is common in older people and nursing home (NH) patients with dementia. Treatment with antidepressants is a clinical priority but the evidence base is sparse and studies demonstrate absence of benefit compared to placebo and increased risk of s everal adverse events in intervention groups. Depression is a common co-morbidity amongst people with chronic pain in form of interactive relationship. Our own research demonstrated efficacy of pain treatment on agitation and aggression in patients with d ementia. Secondary analyses suggest benefit of pain treatment also on depression. It is crucial to follow up these results: DEP.PAIN.DEM (Depression and Pain in Patients with Dementia) a 13 weeks, multicenter, parallel-group, double-blind RCT, aims to inv estigate the efficacy of pain treatment on depression in patients with dementia. Participant (N=266) will be included from 3 old-age psychiatry clinics and from 12 NHs (Bergen, Stavanger, Haugesund). Patients are eligible if they are >59 years, with proba ble or possible dementia (in accordance to NINCDS, ADRDA), coexisting depression (>3 weeks duration) that was assessed as needing antidepressants (CSDD>7), or despite ongoing treatment with antidepressant. Exclusion criteria: Advanced severe medical disea se with expected survival <6 months, severe psychiatric disorder, and severe aggression. Patients will be randomized (1:1) to pain treatment with paracetamol or buprenorphine for 13 weeks, or placebo. Primary and secondary outcomes will be assessed at bas eline, week 2, 4, 8, and 13 using: Cornell; NPI-NH; MOBID-2 Pain Scale; DEMQOL; UKU; MMSE; ADL, and adverse events. Statistics: Chi square-, Mann-Whitney U analyses between groups, ANCOVA, LOCF, ICC, p-values. Collaboration is established between UiB, Sta vanger Univ. Hospital; Karolinska, Stockholm; Kings College, London; and EU-COST-ActionTD1005. We apply for a 4-year project leader (50%) and a PhD-candidate (100%). A comprehensive dissemination plan is availa