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      Oral-Loaded Divalproex Provides Early Efficacy To Treat Acute Mania

      A DGReview of :"The safety and early efficacy of oral-loaded divalproex versus standard-titration divalproex, lithium, olanzapine, and placebo in the treatment of acute mania associated with bipolar disorder"
      Journal of Clinical Psychiatry

      09/26/2003
      By Mary Beth Nierengarten


      Oral-loaded divalproex is safe and provides earlier efficacy over standard-titration drug therapy to treat acute mania in patients with bipolar disorder, reports a study from the United States.

      Patients experiencing acute mania due to bipolar disorder require safe and rapid treatment to stabilise their condition. Increasing initial doses of antimanic mediations is one way being investigated to achieve this.

      In this pooled analysis of 348 patients from 3 randomised clinical trials, Robert MA Hirschfeld, University of Texas Medical Branch at Galveston, Texas, and colleagues evaluated the safety, tolerability, and efficacy of 80 patients randomised to oral-loaded divalproex (20 or 30 mg/kg/day) compared to 87 patients randomised to standard-titration with divalproex (250 mg t.i.d., titrated to 40 to 150 ug/mL), 55 to olanzapine (10 mg q.d. initial dose; titrated up to 20 mg/day), 54 to lithium (300 mg t.i.d., initial dose; titrated up to 0.4 to 1.5 mEq/L) , or 72 to placebo . All patients were inpatients and diagnosed with acute mania due to bipolar illness.

      A significant difference favouring oral loading to standard-titration divalproex was found at 5 days (p=0.017), 7/8 days (p=0.003), and 10 days (p=0.009). Patients treated with oral-loading divalproex had significant improvement over lithium at 7/8 days (p=0.008) and over placebo at 5, 7/8, and 10 days (p<0.001). No differences in efficacy was found between oral-load divalproex and olanzapine.

      Laboratory and clinical measures showed that oral-load divalproex was well-tolerated, and found to be better tolerated than the other active treatments.

      The authors conclude that oral-loading with divalproex provides a more rapid effect on acute mania compared to standard-titration of divalproex, lithium, or placebo, and is better tolerated to all active treatments.


      J Clin Psychiatry 2003;64:7:841-846. "The safety and early efficacy of oral-loaded divalproex versus standard-titration divalproex, lithium, olanzapine, and placebo in the treatment of acute mania associated with bipolar disorder"

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