Dosing of valproate in an elderly population with dementia: Evaluation of discontinuations and dose reductions

Abstract

It is estimated that more than half of elderly patients with dementia will develop some degree of behavioral and psychological symptoms of dementia (BPSD). BPSD is associated with significant morbidity, rapid functional decline, and psychiatric hospitalization, and there are currently no medications approved by the Food and Drug Administration (FDA) for its treatment. One treatment option that has been evaluated is the antiepileptic drug valproate. This retrospective medical record review evaluated the tolerability of valproate in elderly patients with dementia. A total of 62 patients met inclusion criteria for this review, which sought to determine whether there was an association either between the initial valproate dose and discontinuation or dose reduction (DCDR) or the maximum valproate dose achieved and DCDR. Both the total daily dose and total daily dose in mg/kg were assessed. For both the maximum daily dose (OR 1.0; 95% CI 0.99, 1.01) and maximum daily mg/kg dose (OR =1.15; 95% CI 0.92, 1.49) there was also no association with DCDR. There was no associated risk of DCDR when evaluating initial daily doses (OR: 1.0; 95% CI: 0.99 – 1.01). However, an association between DCDR and initial daily mg/kg dose was found (OR: 1.92; 95% CI: 1.11–4.02). For both the initial dose and initial mg/kg dose model, African Americans were associated with the need for DCDR (OR 20.75; 95% CI: 1.77–660). Results from this study suggest that higher initial starting doses based on weight may lead to higher rates of side effects necessitating a discontinuation or dose reduction; however, large trials are needed to confirm these results.