In three meta-analyses of 6, 41, and 21 studies, very few differences were found between lithium and valproate for long-term efficacy in patients with bipolar disorder.2-4 However, evidence from a post hoc analysis of two randomized controlled trials showed that valproate plus placebo was associated with a lower risk of manic relapse compared with lithium, in patients with an index episode of mania.6
References:
1. Kang MG, Qian H, Keramatian K, et al. Lithium vs valproate in the maintenance treatment of bipolar I disorder: a post-hoc analysis of a randomized double-blind placebo-controlled trial. Aust N Z J Psychiatry 2020; 54 (3): 298–307.
2. Cipriani A, Reid K, Young AH, et al. Valproic acid, valproate and divalproex in the maintenance treatment of bipolar disorder. Cochrane Database Syst Rev 2013; 2013 (10): CD003196.
3. Kishi T, Ikuta T, Matsuda Y, et al. Mood stabilizers and/or antipsychotics for bipolar disorder in the maintenance phase: a systematic review and network meta-analysis of randomized controlled trials. Mol Psychiatry 2021; 26 (8): 4146–4157.
4. Yee CS, Vázquez GH, Hawken ER, et al. Long-term treatment of bipolar disorder with valproate: updated systematic review and meta-analyses. Harv Rev Psychiatry 2021; 29 (3): 188–195.
5. Crapanzano C, Casolaro I, Amendola C, Damiani S. Lithium and valproate in bipolar disorder: from international evidence-based guidelines to clinical predictors. Clin Psychopharmacol Neurosci 2022; 20 (3): 403–414.
6. Suppes T, Vieta E, Gustafsson U, Ekholm B. Maintenance treatment with quetiapine when combined with either lithium or divalproex in bipolar I disorder: analysis of two large randomized, placebo-controlled trials. Depress Anxiety 2013; 30 (11): 1089–1098.