A Cochrane review [Abstract] 1 included 6 RCTs with a total of 876 subjects. Five trials enrolled only outpatients; one study recruited only children and adolescents. The trials lasted 6 to 24 months. Two studies (n=312) compared valproate with placebo, 4 studies (n=618) valproate with lithium, one study (n=23) valproate with olanzapine and one study (n=220) valproate with the combination of valproate plus lithium. Valproate was more effective than placebo in preventing study withdrawal due to any mood episode (RR 0.68, 95% CI 0.49 to 0.93; NNTB 8; 2 RCTs, n=312), and no difference in efficacy was found between valproate and lithium (RR 1.02, 95% CI 0.87 to 1.20; 4 trials, n=618). Valproate was associated with fewer participants dropping out of treatment for any cause when compared with placebo or lithium (RR 0.82, 95% CI 0.71 to 0.95; 2 trials, n=312 and RR 0.87, 95% CI 0.77 to 0.98; 4 trials, n=618, respectively). However, combination therapy with lithium plus valproate was more likely to prevent relapse than was monotherapy with valproate (RR 0.78, 95% CI 0.63 to 0.96; 1 trial, n=220). Significant differences in adverse event frequencies were found, and lithium was associated with more frequent diarrhoea, polyuria, increased thirst and enuresis, whereas valproate was associated with increased sedation and infection.
A Cochrane review [Abstract]2 included 25 studies with a total of 3 252 subjects. Valproate had a slightly higher response compared to placebo in the treatment of mania (45% vs 29%, OR 2.05, 95% CI 1.32 to 3.20; 4 studies, n=869). There was little or no difference in response rates between valproate and lithium (56% vs 62%, OR 0.80, 95% CI 0.48 to 1.35; 3 studies, n=356) and valproate and olanzapine (38% vs 44%, OR 0.77, 95% CI 0.48 to 1.25; 2 studies, n=667). The participants receiving valproate were more likely to experience any adverse events compared to placebo (83% vs 75%, OR 1.63, 95% CI 1.13 to 2.36; 3 studies, n=745). There seemed to be little or no difference in tolerability between valproate and lithium (78% vs 86%, OR 0.61, 95% CI 0.25 to 1.50; 2 studies, n=164). The review did not obtain primary tolerability outcome data on the olanzapine comparison. .
Primary/Secondary Keywords