Tolerability of oral loading of divalproex sodium in the treatment of acute mania

Objective: To conduct a pilot study on the safety and tolerability of a dosage strategy for divalproex sodium beginning with 30 mg/kg/day. It is hypothesized that loading at this level will reach therapeutic levels of valproate more quickly, which in turn will decrease the latency of the therapeutic effect. Method: We conducted a retrospective chart review of all acutely manic patients admitted to our facility over a 12-month period. Those inpatients treated with initial divalproex sodium dosages of 30 mg/kg/day for 2 days, followed by 20 mg/kg/day thereafter, were then included in the study. The serum valproate levels and daily Brief Psychiatric Rating Scale (BPRS) scores were documented for each subject. Any adverse changes in daily vital signs, serum liver enzymes, and blood cell counts were noted as well. Nursing and physician notes were then reviewed for any observed or reported adverse effects. Results: Twelve acutely manic inpatients were enrolled in the study. Three subjects did not complete the treatment and are not included in this analysis. The remaining nine subjects completed the treatment, bad a mean decrease in BPRS scores of 55.3%, and were discharged at least in partial remission. Six subjects bad serum valproate levels drawn within 48-72 b of the initial dose, with a mean valproate level of 95.5 mcg/ml. All nine subjects tolerated the treatment reasonably well, with one subject reporting sedation, one reporting sedation and constipation, and one reporting nausea, emesis, and urinary frequency. A transient, asymptomatic decrease in white blood cell count and a low granulocyte count were also noted in one subject. Conclusion: A divalproex dosage strategy beginning with 50 mg/kg/day for 2 days, followed by 20 mg/kg/day thereafter, was reasonably well tolerated in this group of acutely manic patients, even with the concurrent use of other psychotropic medications. Blood levels of 56 to 124 mcg/ml were observed within 3 days after initating treatment.