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September 2008

Valproate for Agitation in Dementia
In two studies, valproate (Depakote and others) did not seem to decrease agitation and aggression in patients with dementia.

Topiramate in the Treatment of Borderline Personality Disorder
Preliminary research suggests topiramate may be useful in the treatment of borderline personality disorder.

In Brief
Generic Risperidone Now Available; Ginkgo biloba Not Effective for Dementia; Autism Linked to Defects in “Learning” Genes

Quetiapine Augmentation in GAD: A Negative Trial
In a recent study, augmenting paroxetine (Paxil and others) treatment of generalized anxiety disorder with quetiapine (Seroquel) was ineffective.

BTP Announces ASCP Partnership
BTP proudly announces our partnership with the American Society of Clinical Psychopharmacology (ASCP) and extends a warm welcome to all ASCP members.

ECGs for Kids with ADHD?
An electrocardiogram may be advisable for some children before they begin pharmacologic treatment for attention-deficit/hyperactivity disorder.

Valproate for Agitation in Dementia

September 2008

Agitation and behavioral disturbances are among the most troublesome behaviors associated with Alzheimer's disease and cause caregivers the greatest distress. Several times recently (BTP 2008;31:1-2, 2007;30:1), we have reviewed treatments, which are far from satisfactory. Encouraging initial results for valproate (Depakote and others) in dementia led to two follow-up studies. Unfortunately, the results are negative.

Tariot and colleagues conducted a double-blind, 6-week trial of divalproex, mean dose 800 ± SD 250 mg/day, in 153 nursing home residents who had probable or possible Alzheimer's disease complicated by agitation.1 Subjects were assigned at random to take divalproex or placebo. Although divalproex was well tolerated, it yielded no apparent behavioral benefits.

In another double-blind study, Herrmann and collaborators compared valproate, up to 1500 mg/day, with placebo in 14 institutionalized patients with moderate to severe Alzheimer's disease.2 These 8 men and 6 women, aged 85.6 ± 4.5 years, received valproate or placebo for 6 weeks in a random-assignment crossover, with a 2-week washout in the middle.

Valproate was associated with more adverse events, including falls, sedation, loss of appetite, thrombocytopenia, and loose stools. Neuropsychiatric inventory of agitation and aggression scores were actually worse when the subjects took valproate than when they received placebo.

The need for treatments to control agitation and aggression in patients with dementia remains acute. As of now, there are no evidence-based treatments—neither pharmacologic nor psychosocial. Valproate does not appear to be helpful for most such patients.

1Tariot PN, Raman R, Jakimovich L, Schneider L, Porsteinsson A, Thomas R, Mintzer J, Brenner R, Schafer K, Thal L, for the Alzheimer's Disease Cooperative Study;Valproate Nursing Home Study Group. Divalproex sodium in nursing home residents with possible or probable Alzheimer Disease complicated by agitation: A randomized, controlled trial. Am J Geriatr Psychiatry 2005;13:942-949.

2Herrmann N, Lanctôt KL, Rothenburg LS, Eryavec G: A placebo-controlled trial of valproate for agitation and aggression in Alzheimer's disease. Dement Geriatr Cogn Disord 2007;23:116-119.