Pharmacological treatments for neuropsychiatric symptoms of dementia in long-term care: a systematic review

CRD summary

The authors concluded that there was limited evidence to support use of some atypical antipsychotics and other medications for neuropsychiatric symptoms in long-term care populations. The authors' conclusions and recommendations for further research and development reflected the paucity of evidence and appear reliable.

Authors' objectives

To review the efficacy and safety of pharmacological treatments for neuropsychiatric symptoms of dementia in long-term care.

Searching

MEDLINE, EMBASE, PsycINFO and The Cochrane Library were searched from January 1980 to February 2011 for publications in English. Search terms were reported. Google Scholar was searched. References of retrieved articles, reviews and guidelines (Canadian Coalition for Seniors' Mental Health, 2006) were handsearched for further studies.

Study selection

Eligible studies were parallel-group randomised controlled trials (RCTs) that compared the effects of pharmacological interventions versus non-pharmacological interventions, another medication or placebo. More than half of the study population had to contain long-term care residents with dementia. Only studies with neuropsychiatric symptoms as their primary outcome were included.

Just over half of the included studies assessed the effects of antipsychotics; others assessed cholinesterase inhibitors, anticonvulsants and other medications. Most of the studies were placebo controlled. All except two of the studies used oral formulations of medicines. Treatment duration ranged from 24 hours to 12 weeks. Mean age of participants per study ranged from 77 to 87 years. Where reported, zero to 92% of the participants were women. Most participants had moderate to severe dementia. Primary outcome measures varied between studies. Safety and tolerability outcomes included all-cause rates of withdrawals, rates of withdrawals due to adverse events and mortality.

Two reviewers independently selected studies for inclusion; any discrepancies were resolved through discussion.

Assessment of study quality

Cochrane Collaboration criteria were used to assess risks of bias associated with random sequence generation, allocation concealment, blinding, completeness of outcome data, selective outcome reporting and other sources of bias. Two independent reviewers rated risk of bias as high, low or unclear.

Data extraction

Data on the primary outcome (change in neuropsychiatric symptoms) and safety- and tolerability-related outcomes were extracted independently by two reviewers. Any discrepancies were resolved through discussion.

Methods of synthesis

Data were presented in a narrative synthesis organised by medication class.

Results of the review

Twenty-nine RCTs were included in the review (4,954 participants, range 14 to 625). High risks of bias were found for funding sources of bias (14 trials), selective outcome reporting (one trial) and incomplete outcome data (one trial). Risks of bias for all other domains were rated as low or unclear (fully reported in paper).

Change in neuropsychiatric symptoms (29 trials): Compared with placebo, statistically significant improvements in neuropsychiatric symptoms were reported by some trials that assessed the efficacy of risperidone (0.5mg/day to 2mg/day; two of six trials) and olanzapine (5mg/day to 10mg/day; two of four trials). Similar results were reported by singular trials of aripiprazole (significance result not reported), carbamazepine (300mg/day), oestrogen (0.625mg to 2.5mg), propanolol (30mg/day to 120mg/day) and prazosin (1mg/day to 6mg/day) (each compared with placebo) and cyproterone (100mg/day) (compared with haloperidol).

Withdrawals, adverse events and mortality: Twenty-four trials assessed rates of all-cause withdrawals, 21 assessed withdrawals due to adverse events and 23 trials assessed mortality. Comparisons with placebos revealed statistically significantly higher rates of all-cause withdrawals for singular trials of 2mg/day risperidone, 2mg/day to 15mg/day aripiprazole, 6mg/day to 12mg/day rivastigmine and 50mg to 100mg quetiapine. A similar, statistically non-significant result was shown when oxcarbazepine (300mg/day to 900mg/day) and placebo were compared. The rate of all-cause withdrawal was statistically significantly lower with propranolol (30mg/day to 120mg/day) than with placebo. Statistically significantly higher rates of withdrawals due to adverse events were shown by singular trials for 2mg/day risperidone, 15mg olanzapine and 10mg/day aripiprazole than with placebo. One study reported that mortality was significantly higher with 1mg/day risperidone than with placebo.

Authors' conclusions

There was limited evidence to support use of some atypical antipsychotics and other medications for neuropsychiatric symptoms in long-term care populations.

CRD commentary

The review question and inclusion criteria were defined clearly. Relevant databases were searched. The restriction to studies published in English may have increased risks of publication and language biases. Efforts were made throughout the review process to minimise reviewer error and bias. Suitable quality assessment criteria were employed and results were reported clearly; studies were mostly of low or unclear risk of bias for the quality domains assessed. The authors acknowledged that almost half of the studies were sponsored by pharmaceutical companies and this increased the risk of reported outcomes being in favour of a company's product. Study details were presented. Clinical and methodological differences between the trials were revealed and these suggested that a narrative method of synthesis was appropriate.

The authors' conclusions and recommendations for further research and development reflected the paucity of evidence and appear reliable.

Implications of the review for practice and research

Practice: The authors stated that known risks of adverse events related to antipsychotics and other psychotropic medications highlighted the requirement for safe, effective alternatives to existing antipsychotics and pharmacological treatments. They suggested that non-pharmacological treatments should continue to be used as first line treatment for neuropsychiatric symptoms with additional consideration of patient and caregiver priorities.

Research: The authors stated that further research was needed to investigate the comparative effectiveness of pharmacological and non-pharmacological treatments in order to better understand benefits and harms associated with treatments for neuropsychiatric symptoms in long-term care.

Funding

Canadian Institutes of Health Research; Queen's University, Canada.

Bibliographic details

Seitz DP, Gill SS, Herrmann N, Brisbin S, Rapoport MJ, Rines J, Wilson K, Le Clair K, Conn DK. Pharmacological treatments for neuropsychiatric symptoms of dementia in long-term care: a systematic review. International Psychogeriatrics 2013; 25(2): 185-203. [PMC free article: PMC3544545] [PubMed: 23083438]

Original Paper URL

http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=8787376

Indexing Status

Subject indexing assigned by NLM

MeSH

Anticonvulsants /administration & dosage /adverse effects; Antidepressive Agents /administration & dosage /adverse effects; Antipsychotic Agents /administration & dosage /adverse effects; Behavioral Symptoms /diagnosis /drug therapy /etiology; Cholinesterase Inhibitors /administration & dosage /adverse effects; Dementia /complications /drug therapy; Diagnostic Techniques, Neurological; Humans; Long-Term Care /methods /statistics & numerical data; Physician's Practice Patterns; Psychiatric Status Rating Scales; Psychomotor Disorders /diagnosis /drug therapy /etiology; Randomized Controlled Trials as Topic; Treatment Outcome

AccessionNumber

12013004025

Database entry date

28/05/2013

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.