The main inhibitory neurotransmitter, GABA, plays an essential role in regulating both dopamine and glutamine. Glutamate and dopamine neurotransmission is thought to be augmented by lithium, aiding in its effect on mood stabilization. Lithium has been shown to reduce both neuronal apoptosis and autophagy, while at the same time increasing neural protective proteins. 4 In addition to mediating neurotransmission and release, much of lithium’s therapeutic action may be related to a reduction in the oxidative stress associated with recurrent episodes of both mania and depression. One study showed that serotonin uptake and release by neurons in rat raphe nuclei were enhanced by greater than 20 percent with the addition of lithium when compared to controls. For example, some evidence points to lithium being synergistic with serotonin neurotransmission. 3 Although Lithium’s specific mechanism of action as utilized to treat psychiatric disorders has not been entirely elucidated and remains partially unknown, several hypotheses exist. A recent meta-analysis also showed that lithium might play an important role in reducing suicide in those with a mood disorder. Most commonly used in the treatment of bipolar disorder, lithium may also be used in refractory depression and schizophrenia or as an adjunct mood stabilizer. Ahead, we will review the pharmacology of lithium, outline its use in modern medicine, and discuss severe lithium neurotoxicity in order to highlight its presentation, diagnosis, and treatment. 2 Although widely used, lithium has a narrow therapeutic window and toxic levels can lead to a variety of systemic symptoms which confer significant morbidity. With an estimated one to three percent of the world’s population suffering from bipolar disorder, lithium’s use is widespread. 1 In bipolar disorder, it is a common adjunct mood stabilizer for patients prone to manic episodes or suicide.

Historically, lithium has been used to treat a range of diseases, including gout and hypertension, but currently it is primarily used to treat bipolar disorder.

Compounds of lithium salts, most commonly lithium carbonate, have been used for medicinal purposes since the 19th century. Lithium is an alkali metal naturally found in minerals and seawater.

Lithium toxicity antidote