Lithium: Fifteen Years Later

Abstract

Background: The 75th anniversary of introducing lithium into modern psychiatry is recognized, attested by the 1949 paper of John Cade. About this event, my editorial in the special 2010 issue of Neuropsychobiology was titled "Lithium: Sixty Years Thereafter." Since then, fifteen more years have brought further information about lithium. This paper makes a narrative review of the most important articles published in this period.

Summary: The selected key literature of 2010-2024 addressed lithium prophylactic efficacy in bipolar disorder (BD), including pediatric, recurrent depression, and lithium augmentation of antidepressants in treatment-resistant depression (TRD). Novel data have been obtained for lithium adverse effects (kidney, thyroid) and beneficial outcomes of long-term lithium administration (anti-suicidal, neuroprotective, antiviral, and others). The results on the mechanisms of lithium action covered genetic investigations of the Consortium of Lithium Genetics (ConLiGen) and in vitro studies with induced pluripotent stem cells and lymphoblastoid cell lines. The underutilization of lithium nowadays was emphasized, and the ways to overcome it were considered.

Key messages: Lithium remains the choice drug for recurrence prevention in BD, also in adolescents, and a significant option for augmentation of antidepressants in TRD. The adverse side effects should be carefully followed and managed according to current guidelines. There are also beneficial lithium impacts, of which anti-suicidal and anti-dementia seem the most important. Most of the results of neurobiological studies on lithium mechanisms may be related to lithium response and some (e.g., immunomodulatory) to the pathogenesis of BD. Better education about lithium could make more patients the beneficiary of this drug.

Keywords: Bipolar disorder; Lithium; Lithium genetics; Lithium response; Mechanisms of action.