Cholinesterase inhibitor discontinuation in patients with Alzheimer's disease: a meta-analysis of randomized controlled trials.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 26646039 · doi:10.4088/JCP.14r09237
What was done
Authors conducted a systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials searched across six databases (MEDLINE, Embase, PsycINFO, Cochrane Library, AMED, and CINAHL) up to March 2014 without language limits. Studies evaluating cholinesterase inhibitor (ChEI) discontinuation versus continuation in patients with standardized Alzheimer's disease diagnoses and measurable neuropsychological outcomes were included. Extracted variables included demographics, setting, ChEI treatment length, discontinuation protocol, follow-up duration (1.5 to 24 months), and double-blind phase dropouts.
What was found
Five RCTs (321 continued, 332 discontinued) were analyzed. Discontinued patients demonstrated significant worsening of cognition (standard mean MMSE difference: -0.29 [95% CI, -0.45 to -0.13], N = 300 continued/307 discontinued, P < .001) and neuropsychiatric symptoms (standard mean NPI difference: -0.32 [95% CI, -0.51 to -0.12], N = 199/211, P = .001), along with higher dropout rates (risk ratio [RR] = 1.33 [95% CI, 1.11 to 1.59], N = 321/332, P = .002). No difference in adverse events was observed (RR = 1.01 [95% CI, 0.85 to 1.20], N = 314/326, P = .92).
Why it matters
Stopping cholinesterase inhibitors in patients with Alzheimer's disease leads to measurable cognitive and behavioral deterioration, supporting the continuation of therapy in established patients.
Limits
The total sample size was relatively small (5 trials, 653 patients). Follow-up duration varied widely from 1.5 to 24 months, and the abstract does not report data on specific ChEI agents, tapering regimens, or baseline disease severity stages.
Cited by
- supports Sudden withdrawal of cholinesterase inhibitors can cause cognitive worsening due to compensatory upregulation of cholinesterase by the body.