Lithium: updated human knowledge using an evidence-based approach: Part I: Clinical efficacy in bipolar disorder

CNS Drugs. 2009;23(3):225-40. doi: 10.2165/00023210-200923030-00004.


Although there has been a decrease in lithium use over several years, it is still recommended as a first-line mood stabilizer in all recent guidelines. It has been argued that many studies of lithium were conducted at a time when study design, assessment standards and the diagnostic criteria for patient selection were not as established as they presently are. However, recent placebo-controlled data from three-arm trials have demonstrated a definite efficacy of lithium in bipolar disorder. Regarding mania, recent trials of novel antimanic treatments (such as second-generation antipsychotics) that have included both placebo and lithium control groups have confirmed that lithium is effective in the treatment of moderate to severe manic episodes. The efficacy of lithium as monotherapy for acute bipolar depression is still controversial, but this therapy is recognized as a therapeutic option. For maintenance therapy, lithium is superior to placebo for the prevention of relapse or recurrence of mood episodes in bipolar I disorder patients with recent manic or hypomanic episodes. Lithium is more effective in preventing episodes of the manic/hypomanic type, including mixed episodes, than preventing depressive episodes. In rapid cycling patients, lithium improves clinical symptoms as efficiently as in nonrapid cycling persons, but is not likely to prevent recurrences. Finally, data from a number of studies suggest that lithium reduces the high suicide rates associated with mood disorders. A well designed cohort study and two independent meta-analyses are in agreement with this finding. In conclusion, most experts, and the most recent guidelines, continue to consider lithium as a keystone therapy of bipolar disorders.

Publication types

  • Review

MeSH terms

  • Animals
  • Antimanic Agents / therapeutic use*
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / mortality
  • Bipolar Disorder / psychology
  • Depressive Disorder / drug therapy
  • Depressive Disorder / psychology
  • Evidence-Based Medicine
  • Humans
  • Lithium Compounds / therapeutic use*
  • Suicide / statistics & numerical data


  • Antimanic Agents
  • Lithium Compounds