The pharmacological treatment of bipolar disorder: the question of modern advances

Harv Rev Psychiatry. Sep-Oct 2010;18(5):266-78. doi: 10.3109/10673229.2010.507042.


Introduction: Lithium has been the mainstay of treatment for patients with bipolar disorder in the United States since 1970. Major treatment guidelines recommend lithium as a first-line treatment for mania and maintenance treatment of bipolar disorder, yet lithium has fallen out of favor while other agents have grown in popularity. The purpose of this review is to examine the evidence for treatments that were available in 1970 and to determine if the field has made any significant advance in the treatment of mania, bipolar depression, and maintenance.

Methods: We conducted a MEDLINE search through 2009, and examined only English-language, randomized/controlled, placebo, or comparison studies. Tolerability as a factor was not considered for this review.

Results: Lithium, valproate, benzodiazepines, and antipsychotics have been reported effective for mania-which was essentially the state of the field in 1970. Despite an FDA indication for the use of lamotrigine for depression and depression maintenance, the supporting evidence is conflicting. For bipolar maintenance, the evidence is overwhelming in support of lithium and very thin for valproate and carbamazepine. There is emerging evidence that several atypical antipsychotics may have efficacy in prevention.

Discussion: The gold standard for treating bipolar disorder in 1970 was lithium, and the gold standard in 2009 remains lithium. Newer agents may increase our armamentarium to some extent, but it is not clear if they represent a major advance in treatment. They still need to be tested against the gold standard.

Publication types

  • Review

MeSH terms

  • Antidepressive Agents / therapeutic use
  • Antimanic Agents / therapeutic use
  • Antipsychotic Agents / therapeutic use
  • Bipolar Disorder / drug therapy*
  • Humans
  • Lithium Compounds / therapeutic use


  • Antidepressive Agents
  • Antimanic Agents
  • Antipsychotic Agents
  • Lithium Compounds