Lithium Associated Side Effects and Neurotoxicity: Is Lithium Neurotoxicity Related to Iron Deposition?

Abstract

Lithium is a mood stabilizer that Australian psychiatrist John Cade and the Swiss Baastrup and Schou's pioneering studies brought in the treatment of bipolar disorder. In current guidelines, it is still considered as first line therapy for acute mania, depression and remission periods. Along with numerous neurotrophic and cytoprotective effects, lithium may rarely cause neurotoxicity. Neuro-toxicity might be related with dose dependent or independent. Mechanism of neurotoxicity has not been identified yet. A possible reason of lithium neurotoxicity is that lithium complicates iron efflux from neurons by inhibiting the tau cascade. Accumulation of iron may increase hydroxyl radical formation, resulting in oxidative neurotoxicity. On the other hand, mechanisms that may alleviate iron deposition should also be considered. This review will address the cardiac and metabolic side effects of lithium and clinical features and biochemical regimes of neurotoxicity, and its relationship with iron accumulation.

Lithium Biological Action Mechanisms after Ischemic Stroke

“…This process hinders the iron efflux from the brain cells and increases the hydroxyl radicals produced by the iron. Lithium has been implicated in various outcomes, such as its effect on the retention of fluids in the hypothalamus [81].…”