A placebo-controlled trial of valproate for agitation and aggression in Alzheimer's disease

Dement Geriatr Cogn Disord. 2007;23(2):116-9. doi: 10.1159/000097757. Epub 2006 Dec 4.


Background/aims: To assess the efficacy and tolerability of valproate for the treatment of agitation and aggression in moderate-to-severe Alzheimer's disease (AD).

Methods: This was a randomized, double-blind, placebo-controlled crossover trial of valproate in institutionalized AD patients. Patients were assessed with the Neuropsychiatric Inventory (NPI) and Cohen-Mansfield Agitation Inventory at baseline and after 6 weeks of treatment with valproate and placebo, with 2 weeks between phases to allow for placebo washout and tapering.

Results: Fourteen patients (8 male/6 female) aged 85.6 +/- 4.5 years with baseline Mini Mental State Examination scores of 4.5 +/- 4.6 and NPI agitation/aggression scores of 6.4 +/- 3.5 were randomized to treatment. NPI agitation/aggression treatment change scores significantly worsened during valproate treatment compared with placebo (Z = -2.03, p = 0.04). Tolerability of valproate was also poor, with patients experiencing a significantly greater mean number of adverse events during valproate therapy compared to placebo (Z = -2.82, p = 0.005).

Conclusion: Valproate is not effective for the management of agitation in moderate-to-severe AD, and may be poorly tolerated in this population.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aggression / psychology*
  • Alzheimer Disease / epidemiology*
  • Alzheimer Disease / rehabilitation*
  • Anticonvulsants / therapeutic use*
  • Cognition Disorders / diagnosis
  • Cognition Disorders / epidemiology
  • Double-Blind Method
  • Female
  • Humans
  • Institutionalization
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Psychomotor Agitation / diagnosis
  • Psychomotor Agitation / drug therapy*
  • Psychomotor Agitation / epidemiology*
  • Severity of Illness Index
  • Valproic Acid / therapeutic use*


  • Anticonvulsants
  • Valproic Acid