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Lithium Therapy, Bipolar Disorder— and Neurocognition

Lithium Therapy, Bipolar Disorder— and Neurocognition

The LithiumeterFigure 1. The Lithiumeter
The Lithium Battery–ClinicalFigure 2. The Lithium Battery–Clinical

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.


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