The Efficacy and Safety of Divalproex Sodium in the Treatment of Acute Mania in Adolescents and Young Adults

This open clinical trial investigated the potential short-term efficacy and safety of divalproex sodium in the treatment of adolescents and young adults with bipolar affective disorder in an acute manic phase. Fifteen subjects were treated for 7 weeks with divalproex sodium (mean drug level in blood +/- the standard deviation at trial completion, 642.85 +/- 183.08 micro mol/liter) and were assessed weekly with the Modified Mania Rating Scale (MMRS), the Brief Psychiatric Rating Scale (BPRS), the Global Assessment Scale (GAS), and the Clinical Global Impressions Scale (CGI). Of the 15 subjects who entered the study, 8 showed marked improvement on the MMRS (pre-post decrease of greater or equal to 75%), 4 showed moderate improvement (pre-post decrease of 50 to 74%), 1 showed some improvement (pre-post decrease of 25 to 49%), 1 showed no improvement and was withdrawn before the seventh study week because of lack of response, and 1 withdrew because of side effects. The mean MMRS score was significantly changed by 7 weeks of treatment in the 13 subjects who completed the 7-week trial (69.54 +/- 24.21 to 18.08 +/- 8.70; t = 7.72; p < 0.0001), as were the BPRS (36.31 +/- 12.22 to 12.00 +/- 4.22; t = 7.53; p < 0.0001), the GAS (30.23 +/- 9.05 to 54.69 +/- 9.40; t = 7.50; p < 0.0001), and the CGI (5.38 +/- 0.96 to 2.38 +/- 0.87; t = 10.01; p <0.0001). Divalproex sodium was generally well tolerated with minimal reports of side effects in study completers. Total scores on the Valproic Acid Side Effects Scale were lower at the end of treatment than at baseline (11.77 +/- 8.99 to 5.46 +/- 3.33; t = 3.04; p < 0.01). We speculate that this was the result of the more accurate reporting of side effects by the adolescents when their manic symptoms were controlled. Three patients developed major side effects during the study that included benign transient elevation of the liver enzymes (N = 1) and sedation and dizziness (N = 1); one showed a decrease to below normal values in peripheral measures of thyroxine and cortisol, which were controlled by lowering the dose of divalproex sodium. (J Clin Psuchopharmacol 1995;15:110-116).