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Evidence summaries

Valproate for Agitation in Dementia

Valproate might possibly be ineffective in treating agitation in people with dementia, but is associated with a higher rate of adverse effects, although the evidence is insufficient. Level of evidence: "D"

A Cochrane review [Abstract] 1 included 5 RCTs with a total of 430 patients with dementia. Studies varied in the dosing of valproate. There is probably little or no effect of valproate over 6 weeks (total BPRS: MD 0.23, 95% CI -2.14 to 2.59; 2 studies, n=202; BPRS agitation factor: MD -0.67, 95% CI -1.49 to 0.15; 2 studies, n=202). Three studies, measuring agitation with the Cohen-Mansfield Agitation Index (CMAI) were consistent with a lack of effect of valproate treatment on agitation. Three studies, which measured cognitive function using the Mini-Mental State Examination (MMSE), found little or no effect of valproate over 6 weeks. Two studies that assessed functional ability using the Physical Self-Maintenance Scale (PSMS) (range 6 to 30) found that there was probably slightly worse function in the valproate-treated group, which was of uncertain clinical importance (MD 1.19, 95% CI 0.40 to 1.98; 2 studies, n=203). A meta-analysis of 3 studies showed that there is a higher rate of adverse effects among valproate-treated participants vs. controls (OR 2.02, 95% CI 1.30 to 3.14; 3 studies, n=381). Pooled analysis of the number of SAEs for the 2 studies indicated that valproate was more likely to cause SAEs (OR 4.77, 95% CI 1.00 to 22.74; 2 studies, n=228). Adverse events that were more frequent for valproate included sedation, gastrointestinal symptoms (nausea, vomiting, and diarrhoea), and urinary tract infections.

Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment, high drop-out rate in the largest trial), inconsistency (heterogeneity in patients, interventions and outcomes) and imprecise results (small studies).

    References

    • Lonergan E, Luxenberg J. Valproate preparations for agitation in dementia. Cochrane Database Syst Rev 2009 Jul 8;(3):CD003945. [PubMed]

Primary/Secondary Keywords