Safety and tolerability of oral loading divalproex sodium in acutely manicbipolar patients

Background: Achieving therapeutic blood levels of a mood stabilizer as quic kly as possible is desirable in patients with acute mania. We examined the feasibility and safety of an accelerated oral loading strategy (divalproex, 30 mg/kg/day, on days 1 and 2, followed by 20 mg/kg/day on days 3-10) desi gned to bring serum valproate concentrations to therapeutic levels (i.e., a bove 50 mu g/mL). Method: Fifty-nine patients who met DSM-TV diagnostic criteria for current manic episode and who had a Mania Rating Scale score greater than or equal to 14 were randomly assigned on a double-blind basis to receive divalproex oral loading (N = 20); divalproex nonloading (N = 20) at a starting dose of 250 mg t.i.d. on days 1 and 2, followed by standard dose titration for day s 3 to 10; or Lithium carbonate (N = 19) at a starting dose of 300 mg t.i.d ., followed by standard dose titration for days 3 to 10. Results: Eighty-four percent of the divalproex-loading patients, but only 3 0% of the divalproex-nonloading patients, had valproate serum levels above 50 mu g/mL at day 3 of the study. None of the lithium-treated patients had serum lithium levels above 0.8 mEq/L at study day 3, No patient was removed from the study because of an adverse event. There were no significant diff erences between the groups in the frequencies or types of adverse events. Conclusion: Accelerated oral loading with divalproex sodium is a feasible a nd safe method to bring serum valproate concentrations to effective levels rapidly.