Efficacy of valproate versus lithium in mania or mixed mania: a randomized, open 12-week trial

Abstract

The objective of this study was to compare the efficacy and safety of valproate and lithium in bipolar I patients experiencing a manic or a mixed episode. This international, randomized, open-label, parallel-group, equivalence study included 268 patients with bipolar I disorder. The starting dose of valproate was 20 mg/kg/day and that of lithium was 800 mg/day. Treatment duration was 12 weeks. The primary outcome measure was mean change in Young Mania Rating Scale score between baseline and study end. Secondary outcome measures were response and remission rates, change in Montgomery and Asberg Depression Rating Scale and Clinical Global Impression Bipolar Disorder instrument score, and occurrence of adverse events. The mean change from baseline in Young Mania Rating Scale score was 15.8+/-5.3 in the lithium group and 17.3+/-9.4 in the valproate group. The 90% confidence interval of the intergroup difference (-0.69; 3.31) was within prespecified equivalence limits. Response rates were 72.6% in the lithium group and 79.5% in the valproate group. Remission rates were 58.5 and 71.9%, respectively. No intergroup differences were observed in median time to treatment response (21 days) or change in Clinical Global Impression Bipolar Disorder instrument or Montgomery and Asberg Depression Rating Scale scores. Adverse events were reported in 42.8% of patients in the lithium group and 41.5% in the valproate group. Valproate and lithium showed comparable efficacy and tolerability in the treatment of acute mania over 12 weeks.

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013

“…The efficacy of lithium and divalproex in the management of acute mania is Yatham et al well established (level 1) (1-3). Two large, 12-week, open, randomized trials comparing lithium to divalproex found comparable efficacy and tolerability of these agents for the treatment of acute mania (46,47).…”

Estimation of resource utilisation difference between lithium and valproate treatment groups from the VALID study

“…Several studies have shown the comparable efficacy and safety of lithium and valproate 10,11 . The sustained antimanic activity of valproate in bipolar disorder [10][11][12] was further confirmed by the VALID study, which showed that valproate and lithium have comparable efficacy and tolerability in the treatment of acute mania over 12 weeks 13 .…”

“…Moreover, published studies to date have largely been limited to North American populations [14][15][16] . To extend these observations to other populations, the VALID study was performed in six Eastern European and South East Asian countries to compare the effectiveness of valproate and lithium treatment in bipolar disorder 13 . The current study was designed as a pragmatic trial in order to determine medical costs in conditions which closely resembled standard clinical practice and would therefore be broadly generalisable.…”

Lithium for bipolar disorder: a review of the recent literature

“…One such RCT comparing aripiprazole, lithium and placebo in BP-I patients with mania or mixed episodes found both lithium and aripiprazole groups had significantly greater improvement compared with placebo after 3 weeks [18]. In another RCT comparing lithium, quetiapine and placebo in mania (n = 302) (excluding mixed episodes) lithium was superior to placebo in both short-and long-term Lithium was superior to placebo in treating mania [16] Yildiz et al [20] Kushner et al [21]. Similarly, another 12-week open randomized parallel group study comparing lithium and valproate in mania found both medications had high response and remission rates with comparable efficacy [22].…”

“…Metabolic effects have been evaluated as outcomes in several studies [19,21,22,24,45-47]; however, one RCT was found specifically addressing metabolic effects. The year-long doubleblind RCT found lithium and aripiprazole had a similar metabolic profile in BP-I patients with a modest increase in body weight, but those with a lower BMI (<25) gained more weight on aripiprazole (p = 0.02) [104].…”