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Limited amount and quality of data on medications for treating neuropsychiatric symptoms of dementia
Clinical Question
Which medications are most effective in treating neuropsychiatric symptoms in adults with dementia?
Bottom line
A small number of studies, disappointing in overall quality, suggest that for managing neuropsychiatric symptoms in adults with dementia, risperidone has the best balance of effectiveness and adverse effects. 2a-
Reference
Study design: Meta-analysis (randomized controlled trials)
Funding: Foundation
Setting: Various (meta-analysis)
Synopsis
These authors searched several databases and registries to identify double-blind randomized trials evaluating at least 2 medications (including placebo) for the management of neuropsychiatric symptoms in adults with dementia. Overall, they included 59 trials with 15,781 participants that evaluated 15 different active treatments. The treatments fell into the following classes: cognitive enhancers, antipsychotics, antidepressants, and mood stabilizers. Most (41%) of the studies enrolled persons with mild-to-moderate dementia; approximately half (52.5%) recruited outpatients; and 6 (10.2%) enrolled nursing home residents. Most studies (86%) were funded by industry. Overall, the risk of bias was high in 12% of the studies, moderate in 61%, and low in 27%. Despite the overall mediocre study quality, the authors chose to pool the data and do a network meta-analysis. The authors reported the main outcomes, various scores for overall improvement and for several neuropsychiatric symptoms, as standardized mean differences (SMDs) where, generally, 0.2 represents a small effect size, 0.5 a medium effect, and 0.8 a large effect size. For overall improvement, risperidone and galantamine were more effective than placebo (SMD -0.20 for each). For reducing aggressive behaviors, the following were statistically significantly more effective than placebo: aripiprazole (SMD -0.31), risperidone (-0.26), divalproex (-0.23), olanzapine (-0.19), and memantine (-0.18). For reducing psychosis, surprisingly, donepezil was the most effective (SMD -0.31), haloperidol was next (-0.27), then aripiprazole (-0.22), and risperidone (-0.15). Patients taking galantamine and rivastigmine were nearly twice as likely as those taking placebo to discontinue treatment for any reason. Drug discontinuation due to adverse effects exceeded placebo for olanzapine (odds ratio [OR] 3.23), divalproex (OR 2.70), galantamine (OR 2.44), rivastigmine (OR 2.27), risperidone (OR 1.75), and donepezil (OR 1.45).
Reviewer
Henry C. Barry, MD, MS
Professor
Michigan State University
East Lansing, MI
Comments
Impact assessment
Excellent
What type of dementia that they have
As a geriatrician seeing and treating neuropsychiatric symptoms of dementia daily, one glaring omission stands out: what type(s) of dementia did these study participants have? The "bottom line" oversimplifies so suggest that antipsychotics would be first line. In fact they can be highly problematic in parkinsonian dementias including Lewy Body. Moreover, the first line treatment - and consistently the most powerful interventions - is non-pharmacologic.