A Randomized, Double-Blind, Placebo-Controlled Pilot Trial of Safety and Tolerability of Two Doses of Divalproex Sodium in Outpatients with Probable Alzheimers Disease

Abstract

These results were used to design the multi-center ADCS trial. Doses of less than 1000 mg/day of divalproex sodium were the maximum tolerated by these outpatients with AD. A larger study of divalproex sodium dose tolerability is needed to define treatment in outpatients with Alzheimer's disease.

Therapeutic Potential of Mood Stabilizers Lithium and Valproic Acid: Beyond Bipolar Disorder

“…A recent case study suggested that low-dose divalproex may reduce the risk of adverse effects and led to behavioral improvement in patients with AD with agitation (Dolder and McKinsey, 2010). A 10-week safety and tolerability study with a sample of 20 outpatients with probable AD revealed that the maximum tolerated dosage of divalproex sodium was ,1000 mg/day, whereas the most common adverse effects were sleepiness and tiredness (Profenno et al, 2005). In patients with mild to moderate AD, divalproex treatment (10-12 mg/kg/day) did not delay the emergence of agitation and cognitive impairment and, more alarmingly, was found to accelerate brain volume loss with significant toxic effects (Tariot et al, 2011).…”

A meta-analysis of mood stabilizers for Alzheimer’s disease

“…The excluded articles referred to 6 clinical studies on mood stabilizers in all types of dementia but not limited to the Alzheimer type [7][8][9][10][11][12] , 2 open studies [13,14] , and 2 studies with insufficient data for analysis [15,16] . Five studies met our inclusion criteria [17][18][19][20][21] . One of these trials originated from Canada [17] , one from England [18] , and the other three originated from the United States [19][20][21] .…”

“…Five studies met our inclusion criteria [17][18][19][20][21] . One of these trials originated from Canada [17] , one from England [18] , and the other three originated from the United States [19][20][21] . With regard to drug, there were one trial of valproate [17] , two of divalproex sodium [20,21] , one of carbamazepine [19] , and one of lithium [18] .…”

Medications and Cognition in Older Adults

“…A randomized study comparing valproate and phenytoin in elderly patients with new-onset epilepsy found no signi fi cant adverse cognitive effects and no difference between the two drugs [ 102 ] . However, a tolerability study of valproate in non-epileptic patients with Alzheimer's disease demonstrated cognitive worsening at a dose of 1,500 mg/day, though doses less than 1,000 mg/ day might be safe [ 103 ] . Carbamazepine was shown to be superior to placebo in treating agitation and aggression in demented nursing home patients with no effects on cognition or functionality [ 104 ] .…”