Question: In patients with dementia, is haloperidol effective for decreasing agitation?
Data sources: Studies were identified by searching the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group, which contains records from 15 databases. Pharmaceutical companies and authors were contacted.
Study selection: 2 reviewers independently selected studies in any language if they were randomized, placebo-controlled trials with allocation concealment and assessment of agitation before and after treatment; if they involved patients who had dementia (unclassified or diagnosed according to criteria) and agitation and treatable causes were ruled out; and if they evaluated haloperidol for > 1 week.
Data extraction: Reviewers assessed the quality of studies and extracted data on patient and study characteristics, interventions, and outcomes (the main outcome was decrease in manifestations of agitation).
Main results: 5 studies (876 patients, mean age range 72 to 82 y, 56% to 67% women) met the selection criteria. 3 studies included outpatients, and 2 studies included institutionalized patients. Treatment duration ranged from 3 to 16 weeks (mean 8.6 wk). Mean doses were categorized as < 2 mg/d and > 2 mg/d (range 0.5 to 6.0 mg/d). In patients with mild or moderate dementia (Mini-Mental State Examination score 12 to 19), the groups did not differ for agitation or global improvement (Table) on any type of measure or dose. Haloperidol, mean dose > 2 mg/d, led to a greater reduction in aggression (2 studies, standardized mean difference in change from baseline score 0.37, 95% CI 0.11 to 0.62) and to more patients with ≥ 1 extrapyramidal symptom or who dropped out because of adverse events by 3 to 6 weeks (1 study) (Table) than did placebo. No difference was seen for akathisia or Parkinsonian gait. For patients with severe dementia, haloperidol, mean dose < 2 mg/d, led to a greater reduction in aggression than did placebo (1 study, mean difference in change from baseline score on the Behavior Pathology in Alzheimer’s Disease Rating Scale–aggression subscale 0.88, CI 0.12 to 1.64).
Conclusion: In patients with dementia, haloperidol reduces aggression but does not reduce agitation and increases some adverse events.
Haloperidol (Hal) vs placebo for moderate or mild dementia*
|Outcomes||Dose||Hal||Placebo||RBI (95% CI)||NNT|
|CGIC improvement at 3 to 4 wk||> 2 mg/d||79%||69%||15% (−2.4 to 36)||Not significant|
|CGIC improvement at 16 wk||< 2 mg/d||32%||31%||5.9% (−47 to 110)||Not significant|
|RRI (CI)||NNH (CI)|
|Dropouts because of adverse events by 3 to 6 wk||> 2 mg/d||17%||5.8%||189% (23 to 589)||10 (5 to 41)|
≥ 1 extrapyramidal symptom by 3 to 6 wk||> 2 mg/d||34%||17%||93% (18 to 219)||7 (4 to 24)|