Paracetamol to enhance quality of life and daily function and to decrease care dependency in advanced dementia: A randomized, double-blind, placebo-controlled crossover trial in long-term care facilities.

Undiagnosed and untreated pain is a serious and frequent problem in persons with advanced dementia, leading to behavioural problems, such as decrease in daily functioning, sleep problems, depression and apathy. In many ways, pain therefore can negatively influence quality of life (QoL). Although pain is difficult to assess in persons with advanced dementia, the impact on QoL is believed to be huge. The long-term care facility (LTCF) organisations of the University Network of the Care sector South Holland (UNC-ZH) find their biggest challenge in preserving QoL in the course of dementia. Until now, there are no proven effective interventions on QoL in persons with dementia in LTCF, as was recently established in a systematic review. However, several interventions are effective in diminishing mediators (such as challenging behaviour and depressed mood) of QoL, including pharmacological treatment of pain. In a large Norwegian nursing home trial, pain treatment was effective in improving agitated behaviour as primary outcome, but also on secondary outcomes such as depression, sleep disturbances and apathy. In addition, Activities of Daily Living (ADL) was improved in the group treated with paracetamol. However, the stepwise approach of treating pain in this trial was not placebo-controlled and did not evaluate outcome measures of QoL. Also, social participation can be seen as a mediator for QoL, and has been shown to benefit from administration of paracetamol. However, so far no intervention studies are available that investigated the effects of pain management on QoL in advanced dementia directly. In addition, recent studies suggest that pain has a negative impact on the course of ADL function. The overall aim of this study is to achieve optimal QoL and ADL function in LTCF residents with moderate to very severe dementia and moderate QoL, and to achieve less care dependency through pain treatment with paracetamol. Objectives 1.Evaluate the effect of regularly scheduled administration of pain treatment (paracetamol) on QoL in LTCF residents with moderate to severe dementia. 2.Evaluate the effect of pain treatment (paracetamol) on ADL function and care dependency. 3.Evaluate the effect of paracetamol on pain, change in challenging behaviour and antipsychotic medication use. Research questions 1.What is the effect of regularly scheduled administration of paracetamol on the QoL of older persons with moderate to severe dementia in LTCF? 2.What is the effect of regularly scheduled administration of paracetamol on functioning in ADL and care dependency in this population? 3.What is the effect of regularly scheduled administration of paracetamol on pain, change in challenging behaviour and antipsychotic medication use? Study design: A randomized, double-blind, placebo-controlled crossover trial. Primary outcome:The difference between baseline QoL and follow-up scores (QUALIDEM and DS-DAT). Secondary outcomes: NPI-NH, Katz, care dependency, Reisberg Global Deterioration Scale, pain (MOBID-2, COST-pain instrument), and medication use, all compared to baseline. Intervention: Orally administered paracetamol at a maximum dose of 3 grams (3x2 tablets 500 mg) daily or corresponding placebo. Each treatment period is for six weeks, separated by a washout period of 7 days. Subject selection: Subjects will be recruited from the UNC-ZH (42 LTCF) and are eligible to participate when (1) diagnosis of dementia, Reisberg Global Deterioration Scale 5-7, (2) age >65 years, and (3) QUALIDEM score <60 and (4) not using any pain medication one week before start study. Excluded: (1) presence of a severe psychiatric disorder, (2) a life expectancy <6 months, (3) allergy to study drugs, (4) severe liver insufficiency/disease, use of >4 units alcohol per day. Measurements: Baseline (0 weeks), 6 weeks and baseline (7 weeks) and 13 weeks: comorbidity (only at baseline), daily functioning (Katz), care dependency (CDS), the Neuropsychiatric Inventory–Nursing Homes (NPI-NH), QoL (QUALIDEM, DS-DAT), medication use, pain (MOBID-2, COST pain instrument: PAIC), side-effects. Statistical considerations: To detect an interindividual difference of 10% QUALIDEM score with 80% power and alpha 0.05, we calculated a required sample of 70 residents. We assume an intraindividual standard deviation of 13 points, as derived from a previous study (STA-Op! Study, Pieper,et al., unpublished). Estimating a drop-out of 30% (mortality, loss to follow-up from other reasons, unwillingness to participate, paracetamol use, existing pain and discharge from LTFC) and invalid measurements of 5%, we will randomise 95 residents. This study will lead to a thesis and will generate knowledge that will be implemented in the comprehensive training program for elderly care physicians and guidelines. It also strengthens the cooperation between the LUMC and Bergen University, and the European COST cooperation Pain and Impaired cognition, Especially dementia.