Cochrane for Clinicians

Putting Evidence into Practice

Lithium for Acute Mania


Am Fam Physician. 2020 May 1;101(9):528-529.

Author disclosure: No relevant financial affiliations.

Clinical Question

Is lithium a safe and effective therapy for episodes of acute mania?

Evidence-Based Answer

Lithium is more effective at inducing a reduction of at least 50% on the validated Young Mania Rating Scale (YMRS) compared with placebo (number needed to treat [NNT] = 6; 95% CI, 5 to 8; six studies; n = 1,707). (Strength of Recommendation [SOR]: A, based on consistent, good-quality patient-oriented evidence.) Most comparisons of lithium with mood stabilizers and antipsychotics demonstrate little to no difference in effectiveness; however, olanzapine (Zyprexa) is slightly more effective than lithium. When compared with placebo, lithium increases the risk of tremor (number needed to harm [NNH] = 11; 95% CI, 7 to 21; six studies; n = 1,241) and somnolence (NNH = 19; 95% CI, 10 to 50; seven studies; n = 1,351).1 (SOR: A, based on consistent, good-quality patient-oriented evidence.)

Practice Pointers

Bipolar disorder is a common disease in which patients experience some combination of depressed mood, elevated mood (mania), and mixed states. Lithium is effective as a maintenance drug in bipolar disorder, acting as a mood stabilizer and decreasing the risk of suicide.

This Cochrane review evaluated lithium as a first-line therapy for acute mania, and included 36 randomized controlled trials and 4,220 patients.1 Three of the studies included patients younger than 18 years. The other studies included male and female patients of any age with bipolar disorder who fit criteria for a manic episode. The studies compared lithium with placebo, electroconvulsive therapy, and 12 other medications over three to 12 weeks. The study authors used odds ratios to analyze binary efficacy outcomes.

A positive response was substantiated by a reduction of at least 50% in symptoms on the YMRS. Patients who had acute mania treated with lithium vs. placebo were more likely to achieve this effect (NNT = 6; 95% CI, 5 to 8; six studies; n = 1,707). Lithium also allowed patients to achieve remission of acute mania

Author disclosure: No relevant financial affiliations.


1. McKnight RF, de La Motte de Broöns de Vauvert SJGN, Chesney E, et al. Lithium for acute mania. Cochrane Database Syst Rev. 2019;(6):CD004048.

2. Dols A, Sienaert P, van Gerven H, et al. The prevalence and management of side effects of lithium and anticonvulsants as mood stabilizers in bipolar disorder from a clinical perspective: a review. Int Clin Psychopharmacol. 2013;28(6):287–296.

3. National Institute for Health and Care Excellence. Bipolar disorder: assessment and management. Clinical guideline [CG185]. Updated February 2020. Accessed April 6, 2020.

These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, assistant medical editor.

A collection of Cochrane for Clinicians published in AFP is available at



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