THE EFFICACY AND SAFETY OF DIVALPROEX SODIUM IN THE TREATMENT OF ACUTE MANIA IN ADOLESCENTS AND YOUNG-ADULTS - AN OPEN CLINICAL-TRIAL

This open clinical trial investigated the potential short-term efficac y 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 a the standard deviation at trial completion, 642 .85 +/- 183.08 mu mol/liter) and were assessed weekly with the Modifie d Mania Rating Scale (MMRS), the Brief Psychiatric Rating Scale (BPRS) , the Global Assessment Scale (GAS), and the Clinical Global Impressio ns Scale (CGI). Of the 15 subjects who entered the study, 8 showed mar ked improvement on the MMRS (pre-post decrease of greater than or equa l to 75%), 4 showed moderate improvement (pre-post decrease of 50 to 7 4%), 1 showed some improvement (pre-post decrease of 25 to 49%), 1 sho wed no improvement and was withdrawn before the seventh study week bec ause of lack of response, and 1 withdrew because of side effects. The mean MMRS score was significantly changed by 7 weeks of treatment in t he 13 subjects who completed the 7-week trial (69.54 +/- 24.21 to 18.0 8 +/- 8.70; t = 7.72; p < 0.0001), as were the BPRS (36.31 +/- 12.22 t o 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 2.3 8 +/- 0.87; t = 10.01; p < 0.0001). Divalproex sodium was generally we ll tolerated with minimal reports of side effects in study completers. Total scores on the Valproic Acid Side Effects Scale were lower at th e 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 mani c symptoms were controlled. Three patients developed major side effect s during the study that included benign transient elevation of the liv er enzymes (N = 1) and sedation and dizziness (N = 1); one showed a de crease to below normal values in peripheral measures of thyroxine and cortisol, which were controlled by lowering the dose of divalproex sod ium.