A double-blind comparison of valproate and lithium in the treatment of acute mania

TLDR

The study compared lithium carbonate and valproate for treating acute mania and examined whether pretreatment clinical features, such as mixed affective states, predict differential drug response. Twenty‑seven DSM‑III‑R manic patients were randomized in a 3‑week double‑blind trial, with symptom severity assessed by SADS‑C, GAS, and BPRS and drug effects analyzed via repeated‑measures ANOVA. Both medications improved mania, lithium was slightly more effective overall, and valproate’s benefit was linked to high pretreatment depression scores and mixed affective states, indicating that valproate may be especially useful for patients with mixed presentations.

Abstract

This study was carried out to compare the efficacy of lithium carbonate with that of valproate in acute mania and to determine whether pretreatment clinical characteristics, such as the presence of a mixed affective state, might predict a differential response to the two drugs.Twenty-seven patients meeting DSM-III-R criteria for acute manic episodes underwent a 3-week, randomized, double-blind, parallel-groups trial of treatment with lithium carbonate or valproate. Symptom severity was measured by using the Schedule for Affective Disorders and Schizophrenia, change version (SADS-C), the Global Assessment Scale (GAS), and the Brief Psychiatric Rating Scale (BPRS). Drug effects were compared by using repeated measures analysis of variance (ANOVA).At the end of the study, nine of 14 patients treated with valproate and 12 of 13 patients treated with lithium had responded favorably, as measured by changes in the SADS-C mania, BPRS, and GAS scores. Elevated pretreatment SADS-C depression scores were associated with good response to valproate. ANOVA revealed a significant interaction between drug and mixed affective state with respect to treatment response.Lithium and valproate were both effective in improving manic symptoms, and lithium was slightly more efficacious overall. Unlike the case with lithium, favorable response to valproate was associated with high pretreatment depression scores. Therefore, treatment with valproate alone may be particularly effective in manic patients with mixed affective states.