Lithium has a global history—discovered initially by Danish siblings (Carl and James Lange) in the 19th century and then rediscovered as a treatment for manic-depressive illness in the mid-20th century by John Cade, an Australian. Sometime later, following publication of the first clinical trials, lithium was introduced to clinical practice in the US and across Europe.
In clinical practice, functional mood stability—which can on occasion be achieved with optimum lithium therapy—is the gold standard that both clinicians and patients strive to attain. To facilitate this endeavor, guidelines on lithium therapy have become increasingly sophisticated; they not only provide therapeutic indications and plasma levels with respect to efficacy, but also inform practitioners about how potential adverse effects can be minimized or avoided.
Margaret, a 36-year-old with bipolar I disorder, is referred for an appraisal of treatment strategies following the resolution of an episode of depression. Although the episode was relatively moderate in severity and she did not require hospitalization, suicidality featured strongly during the episode. She currently takes 1000 mg of lithium and 400 mg of lamotrigine daily.
She reports that her mood is better but says that she has been “slowing down at work.” She is finding it difficult to perform mental arithmetic, something she had previously been very adept at doing. She is assessed for cognitive symptoms using the Lithium Battery–Clinical; in addition, a battery of cognitive tests reveals scores in the normal range. Her plasma lithium level (0.7 mmol/L) is within the normal range for maintenance therapy.
Given the presence of manic-mixed features and a recent episode occurrence, as well as subjective chronic cognitive impairment, it is recommended that valproate be substituted for the lamotrigine. Once the transition takes place, the dose of lithium is gradually decreased to achieve a plasma level of 0.5 mmol/L. During this period, Margaret regularly visits her primary physician for clinical assessment and monitoring. She is understandably anxious about the changes to her medication regimen but maintains mood stability and only reports anticipated adverse effects.
When re-evaluated by her regular psychiatrist after 2 weeks, Margaret reports noticeable improvement in her cognitive symptoms. Twelve months later, Margaret remains well and continues to work full time. She is monitored regularly and comprehensively every 3 months.
Professor Malhi is Head of the Department of Psychiatry, Royal North Shore Hospital, and Chair of Psychiatry, University of Sydney, Australia. Dr. Outhred is Postdoctoral Research Associate, Department of Psychiatry, Royal North Shore Hospital, University of Sydney. Professor Malhi and Dr. Outhred have received grant or research support from the National Health and Medical Research Council, Ramsay Health, American Foundation for Suicide Prevention, and Sydney Medical School Foundation. Professor Malhi has received grant or research support from NSW Health, AstraZeneca, Eli Lilly & Co, Organon, Pfizer, Servier, and Wyeth; he has been a speaker for AstraZeneca, Eli Lilly & Co, Janssen Cilag, Lundbeck, Pfizer, Ranbaxy, Servier, and Wyeth; and he has been a consultant for AstraZeneca, Eli Lilly & Co, Janssen Cilag, Lundbeck, and Servier.
Note: The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the American Foundation for Suicide Prevention.
1. Grof P. Excellent lithium responders: people whose lives have been changed by lithium prophylaxis. Lithium. 1999;50:36-51.
2. Malhi GS, Gershon S, Outhred R. Lithiumeter: version 2.0. Bipolar Disord. 2017 (in press). Accepted for publication October 27, 2016.
3. Hayes JF, Marston L, Walters K, et al. Adverse renal, endocrine, hepatic, and metabolic events during maintenance mood stabilizer treatment for bipolar disorder: a population-based cohort study. PLoS Med. 2016;13:e1002058.
4. Malhi GS, Bassett D, Boyce P, et al. Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders. Aust N Z J Psychiatry. 2015;49:1087-1206.
5. Goodwin GM, Haddad PM, Ferrier IN, et al. Evidence-based guidelines for treating bipolar disorder: revised third edition recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2016;30:495-553.
6. Bauer M, Gitlin M. The Essential Guide to Lithium Treatment. New York: Springer International Publishing; 2016.
7. Malhi GS, Outhred T. Therapeutic mechanisms of lithium in bipolar disorder: recent advances and current understanding. CNS Drugs. 2016;30:931-949.
8. Kessing LV, Forman JL, Andersen PK. Does lithium protect against dementia? Bipolar Disord. 2010;12:87-94.
9. Kessing LV, Sondergard L, Forman JL, Andersen PK. Lithium treatment and risk of dementia. Arch Gen Psychiatry. 2008;65:1331-1335.
10. Cipriani A, Hawton K, Stockton S, Geddes JR. Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis. BMJ. 2013;346:f3646.
11. Mauer S, Vergne D, Ghaemi SN. Standard and trace-dose lithium: a systematic review of dementia prevention and other behavioral benefits. Aust N Z J Psychiatry. 2014;48:809-818.
12. Malhi GS, Bargh DM, Kuiper S, et al. Modeling bipolar disorder suicidality. Bipolar Disord. 2013;15:559-574.
13. Malhi GS, McAulay C, Gershon S, et al. The Lithium Battery: assessing the neurocognitive profile of lithium in bipolar disorder. Bipolar Disord. 2016;18:102-115.
14. Malhi GS, Ivanovski B, Hadzi-Pavlovic D, et al. Neuropsychological deficits and functional impairment in bipolar depression, hypomania and euthymia. Bipolar Disord. 2007;9:114-125.
15. Torres IJ, Malhi GS. Neurocognition in bipolar disorder. In: Yatham LN, Maj M, eds. Bipolar Disorder: Clinical and Neurobiological Foundations. Chichester, UK: John Wiley & Sons, Ltd; 2012:69-82.