Efficacy and tolerability of lithium for the treatment of acute mania in children with bipolar disorder: A systematic review: A report from the ISBD-IGSLi joint task force on lithium treatment

Bipolar Disord. 2018 Nov;20(7):583-593. doi: 10.1111/bdi.12690. Epub 2018 Sep 16.


Objectives: To assess the efficacy and tolerability of lithium for the treatment of acute mania in children and adolescent diagnosed with bipolar disorder.

Methods: A systematic literature search up to August 2017 was conducted for clinical trials that included lithium in males and females up to 18 years of age with a diagnosis of bipolar disorder and experiencing a manic or mixed episode according to standardized diagnostic criteria. The protocol was registered in PROSPERO (CRD42017055675).

Results: Four independent studies described in seven manuscripts met the inclusion criteria. Overall, 176 patients were treated with lithium either as a monotherapy or adjunct to risperidone. Efficacy results suggest that lithium may be superior to placebo (standardized mean difference [SMD] -0.42, 95% confidence interval [CI] -0.88 to 0.04), comparable to sodium divalproex (SMD -0.07, 95% CI: -0.31 to 0.18), but significantly less effective than risperidone for treating protracted manic/mixed episodes and comorbid attention-deficit hyperactivity disorder (ADHD) in prepubertal children (SMD 0.85, 95% CI: 0.54 to 1.15). Lithium was not associated with serious adverse events, and was generally well tolerated with common side effects similar to those reported in adults.

Conclusions: Limited data suggests that lithium may be an effective and tolerable treatment for some forms of paediatric mania. However, lithium is clearly inferior in efficacy to risperidone in prepubertal patients diagnosed with protracted manic/mixed episodes and comorbid ADHD. There is a lack of data concerning the efficacy and tolerability of lithium as an acute treatment for classical mania in adolescents and important clinical issues remain unaddressed.

Keywords: adolescents; bipolar disorder; children; efficacy; lithium; mania; manic episode; meta-analysis; systematic review; tolerability; treatment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adolescent
  • Antimanic Agents / pharmacology
  • Bipolar Disorder / drug therapy*
  • Child
  • Female
  • Humans
  • Lithium Compounds / pharmacology*
  • Male
  • Treatment Outcome


  • Antimanic Agents
  • Lithium Compounds