Lithium for bipolar disorder: a review of the recent literature

Abstract

Lithium is a commonly prescribed treatment for bipolar disorder. Many early studies on which its use has been historically based no longer meet current research standards. A large number of studies with more modern designs have been recently published warranting a review. New research adds to the evidence for lithium’s efficacy in mania and maintenance. There is also additional evidence, albeit less robust, to support its benefit in bipolar depression and mixed episodes. Meta-analyses of mainly observational data have found reduced suicidal behavior in bipolar patients taking lithium. Careful monitoring and prescribing can reduce the risk of adverse effects.

Keywords::

• bipolar disorder
• dosing
• efficacy
• lithium
• predictors of response
• suicide

Acknowledgements

The authors would like to thank J Cheng and J Ramiriz for their assistance on a small part of the literature search for this review. They would also like to thank T da Silva for her administrative support.

Financial & competing interests disclosure

A Ravindran has received grant awards from Cephalon, Eli Lilly, GlaxoSmithKline, Janssen-Ortho, Pfizer, Roche, Servier and Wyeth, AstraZeneca, Lundbeck and Pfizer and has also served as a consultant for the above institutions and on their Advisory Boards. G Curran has previously received grants from the RANZCP, New South Wales Institute of Psychiatry and MIGA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Much of the early literature on lithium no longer meets current research standards. Furthermore, interpretation of the early research is clouded by changes in the bipolar diagnostic criteria over time.

• There has been a great increase in the literature on lithium used to treat bipolar disorder over the last 20 years, particularly as a result of lithium being used as a gold standard comparator to newer medications.

• New RCTs and meta-analyses continue to support lithium’s efficacy in maintenance and mania. There is evidence supporting its efficacy in mixed and depressive episodes, but it is less robust.

• Lithium’s usefulness can be limited by its relatively slower onset of action, the need for venipuncture, a narrow therapeutic index and adverse effects.

• Many serious adverse effects can be avoided with careful monitoring and prescribing according to guidelines.

• There has been a shift from multiple daily dosing toward single daily dosing.

• Meta-analyses have found long-term lithium reduces the risk of suicide in people with mood disorders.

• Pharmaocogenetics is a promising area of lithium research that may ultimately lead to better predictions of who is likely to respond well to lithium.