2 August 2011
A randomised controlled trial suggests that a systematic approach to the management of pain in people with dementia reduces agitation and may reduce the number of unnecessary prescriptions for antipsychotic drugs.
Level of evidence:
Level 2 (limited quality patient-oriented evidence) according to the SORT criteria.
Underlying health problems, of which pain is just one example, should be considered as one of the potential causes of behavioural problems in people with dementia and should be managed appropriately. The WHO pain ladder provides a useful basis for the management of pain.
As summarised in MeReC Rapid Review number 3471, there are a number of useful resources, building on the NICE/SCIE guideline for the management of people with dementia who develop behavioural and psychological symptoms. These provide best practice advice for health professionals when managing people with dementia. In addition to these, a Best Practice Guide, ‘Optimising treatment and care for people with behavioural and psychological symptoms of dementia‘, has been published and is endorsed by the Department of Health. Analgesics (paracetamol 1 g up to 4 times a day) is one of the pharmacological treatment options recommended in the best practice guide, which can be attempted on a trial basis where other specific interventions have been unsuccessful and symptoms are causing extreme distress or risk.
What is the background to this?
There are approximately 750,000 people with dementia in the UK, approximately one third of whom live in care homes. More than 90% of people with dementia will experience behavioural and psychological symptoms of dementia, which include agitation, aggression, hallucinations and delusions. Agitation is a cause of distress to people with dementia and a burden to family and carers, and is one of the most challenging symptoms to manage. As emphasised in the Banerjee report, antipsychotic drugs are often and inappropriately used as first-line treatment for behavioural and psychological symptoms of dementia.
Many people with dementia have painful conditions, about which they may have difficulty in communicating, and their pain can manifest as agitation. More effective treatment of undiagnosed pain may contribute, therefore, to the overall prevention and management of agitation. The present study evaluated whether the systematic use of analgesics could reduce agitation in people with moderate to severe dementia who were living in nursing homes in Norway.
What does this study claim?
This study was a cluster randomised controlled trial of 352 nursing home residents with moderate to severe dementia. It compared daily treatment of pain for eight weeks according to a stepwise analgesic protocol (paracetamol, morphine, buprenorphine transdermal patch, or pregabalin) with usual treatment. In the intervention group, 69% of patients received only paracetamol (from this protocol) at a maximum dose of 3 g/day (Step-1). Agitation was statistically and clinically significantly reduced in the intervention group compared with control group. After eight weeks there was an average difference of −7.0 (95% confidence interval [CI] −3.7 to −10.3) in scores for agitation (Cohen-Mansfield agitation inventory [CMAI]) between the treatment group (p < 0.001). The CMAI is a questionnaire consisting of 29 agitated behaviours, each rated on a 7 point scale of frequency (range 29 to 203). Treatment of pain was also significantly beneficial for the overall severity of neuropsychiatric symptoms and pain, but the groups did not differ significantly for activities of daily living or cognition.
The authors conclude that effective management of pain can play an important part in the treatment of agitation and could reduce the number of unnecessary prescriptions for psychotropic drugs in the population studied.
How does this compare with other studies.
Other less robust studies have shown some support for the potential benefit of managing agitation by treating unmet needs such as pain, but with considerable differences in the magnitude of benefit. This study is claimed to be the first adequately powered parallel group randomised controlled trial of pain management for the treatment of agitation in people with moderate to severe dementia. According to an accompanying editorial, the results compare favourably to the equivocal results of treatment for agitation using antipsychotics, acetylcholinesterase inhibitors, and memantine.
The NICE/SCIE guideline for dementia recommends that people with dementia who develop non-cognitive symptoms that cause them significant distress or who develop behaviour that challenges should be offered an assessment at an early opportunity to establish likely factors that may generate, aggravate or improve such behaviour. The assessment should be comprehensive and include, among others, possible undetected pain or discomfort. No specific recommendations are provided with regard to analgesic regimens, however, the present study provides evidence that a systematic pain management protocol, starting with paracetamol, may help in treating agitation in people with dementia.
Building on the recommendations in the NICE/SCIE guideline, a best practice guide, ‘Optimising treatment and care for people with behavioural and psychological symptoms of dementia‘, was recently published and is endorsed by the Department of Health. The guide provides advice to health and social care professionals on how to treat behavioural and psychological symptoms (such as agitation and depression) with the aim of preventing inappropriate prescriptions of antipsychotics.
Many people with dementia and mild or moderate behavioural and psychological symptoms may respond to a period of watchful waiting, and the Best Practice Guide initially recommends this approach — a four-week proactive period of ongoing assessment and simple non-drug treatments. If behavioural or psychological symptoms have not improved through watchful waiting, it is appropriate to try a specific intervention that is more tailored to the individual, with psychosocial interventions being attempted before any pharmacological treatment. If all other specific interventions have been unsuccessful and symptoms are causing extreme distress or risk then a trial of a pharmacological treatment targeted at behavioural and psychological symptoms may be attempted. An analgesic (paracetamol up to 4 g/day) is one of the options that is recommended in the Best Practice Guide for use on a trial basis, alongside antipsychotics, anticonvulsants and antidepressants,
The harms and limited benefits of using antipsychotic drugs for the treatment of people with dementia who exhibit challenging behaviours are well recognised. They have been the subject of several previous reviews and MHRA warnings, and are associated with both first (typical) and second (atypical) generation antipsychotics (see MeReC Rapid Review No. 847). In November 2009, the Banerjee report suggested that up to about a quarter of patients with dementia are taking low dose antipsychotics, and that antipsychotics are too often used as a first-line response to behavioural difficulty in dementia rather than as a considered second-line treatment when other non-pharmacological approaches have failed. Analgesics may be an effective and safer alternative option to the use of antipsychotics for some patients. Most of the patients in the present study received paracetamol, which is a particularly safe and effective analgesic in frail elderly patients.
The present study is not without limitations. The cluster randomisation design was used, as it was not considered appropriate for care staff in the individual nursing homes to treat individual residents differently. However, this design raises the raise the possibility that there were other differences in the management of patients in different homes, which were not randomly distributed. The study was not double-blind, although staff carrying out assessments of outcomes were blinded to the treatment allocation. Although attempts were made to ensure that staff in direct care contact with participants were unaware of the type of medications, the authors recognise the difficulty of fully blinding research assistants and caregivers to group allocation. Twenty-six percent of patients received opioid analgesics and it can not be ruled out that sedation might explain some of the reduction in agitation in the intervention group. Although there is evidence from this study that analgesics can be an effective means of reducing agitation, it provides no direct evidence that this approach is more or less effective than other treatment strategies, including systematic non-drug based interventions.
Cluster randomised controlled trial. There were 60 clusters (single independent nursing home units) in 18 nursing homes within five municipalities of western Norway.
352 residents of nursing homes with moderate to severe dementia and clinically significant behavioural disturbances. Mean ages (intervention group first): 85 years, 87 years; women: 75%, 74%; Median CMAI scores: 53 (range 39 to 126), 51 (range 39 to 114); Median MMSE: 7(range 0 to 20); 8 (range 0 to 20).
Intervention and comparison
Participants were randomised to a stepwise protocol for the treatment of pain for eight weeks with additional follow-up four weeks after the end of treatment (33 clusters; n=175) or to usual treatment (control, 27 clusters; n=177). Treatments included in the stepwise protocol (Steps 1 to 4, respectively) were: paracetamol (max dose 3g/day); morphine (5mg twice daily, max. dose 10mg twice daily); buprenorphine transdermal patch (5microgram/hour, max 10microgram/hour); pregabalin (25mg once daily, max dose 300mg/day).
Outcomes and results
Agitation was significantly reduced in the intervention group compared with control group after eight weeks (repeated measures analysis of covariance with last observation carried forward adjusting for baseline score, P<0.001). Mean CMAI total scores reduced from 56.2 to 52.8 in the control group and from 56.5 to 46.9 in the intervention group. The average relative reduction in CMAI total score was 17% (treatment effect estimate −7.0, 95% CI −3.7 to −10.3). In the four weeks following cessation of the intervention, CMAI scores increased to a mean of 52.5 and 50.3 respectively, and the mean difference (–3.2) was no longer statistically significantly different (P=0.06).Treatment of pain was also significantly beneficial for the overall severity of neuropsychiatric symptoms (neuropsychiatric inventory-nursing home version total score: −9.0, 95%CI −5.5 to −12.6; P<0.001) and pain (mobilisation-observation-behaviour-intensity dementia-2 pain scale total score −1.3, 95%CI −0.8 to −1.7), but the groups did not differ significantly for activities of daily living or cognition.
The study was funded by the Norwegian Research Council, the University of Bergen, and Kavli’s Research Centre for Ageing and Dementia, Norway.
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