Effects of divalproex sodium on hemoglobin level

A small number of molecular and clinical studies found an association between increases in fetal hemoglobin concentration and valproate (VPA) use. However, the effect of VPA on total hemoglobin (Hb) level has not been studied. We herein review a randomized, double-blind, parallel group, multicenter, concentration–response design trial that compared the safety and efficacy of target trough plasma VPA concentrations in patients with complex partial seizures treated with divalproex sodium as monotherapy. Trough VPA concentrations and concomitant Hb levels that were drawn at baseline and intermittently throughout a 24-week period were analyzed. A total of 549 trough plasma VPA levels and concomitant total Hb levels were analyzed. Correlation between all study variables (gender, age, trough plasma VPA level, duration of exposure, baseline Hb level) and change in total Hb level showed that only baseline Hb level was a significant factor (inverse relationship). Hb increase was evident in 47.0% of values. A clinically relevant increase in Hb (> 0.5 g/dL) occurred in 23.9% of values. VPA is associated with a change in total Hb level that correlates inversely with baseline Hb levels.