Valproate doesn't prevent Alzheimer's agitation, psychosis

NEW YORK , 06 aug 2011- Divalproex sodium (Depakote) does not delay the onset of agitation or psychosis in patients with Alzheimer's disease, nor does it slow the progression of dementia, recent data show.

The new findings, along with inconclusive results of preliminary studies and negative results in a large trial reported in 2005, "should discourage prophylactic or symptomatic use of valproate in dementia," the researchers wrote this month in Archives of General Psychiatry.

The drug is not formally approved for Alzheimer's disease, but it's often recommended. For example, guidelines from the American Academy of Family Physicians list it as a preferred chronic medication for managing anger or aggression in Alzheimer's patients.

For the current study, Dr. Pierre N. Tariot at the Banner Alzheimer's Institute in Phoenix, Arizona and colleagues enrolled 313 Alzheimer's patients in a randomized double-blind trial. None of them had yet developed agitation or psychosis.

For 24 months, participants received either placebo or valproate, at a target dose of 10-12 mg/kg/day. Ultimately, 122 subjects completed 24 months on study medication.

The primary endpoint -- a score of 3 or more on at least one of the Neuropsychiatric Inventory (NPI) items assessing delusions, hallucinations, and agitation/aggression - was met by 29 patients receiving placebo and 25 taking valproate, a nonsignificant difference.

In addition, the change in Alzheimer Disease Assessment Scale-cognitive subscale scores at 12 months favored placebo treatment, according to the report.

Furthermore, the valproate group had higher rates of somnolence, gait disturbance, tremor, diarrhea, constipation, weakness, asthenia, and dyspnea.

Behavioral problems in Alzheimer's disease still await a solution. "Given the public health significance of the behavioral features of dementia and the limited safety and efficacy of available psychotropic agents, it is still appropriate to pursue the goal of secondary prevention of agitation and psychosis," the authors said. "Other agents may merit investigation with this type of trial design."

SOURCE: http://bit.ly/pgmLgc

Arch Gen Psychiatry 2011;68:853-861.