The syndrome of irreversible lithium-effectuated neurotoxicity

Clin Neuropharmacol. 2005 Jan-Feb;28(1):38-49. doi: 10.1097/01.wnf.0000150871.52253.b7.


Objectives: Persistent sequelae of lithium intoxication gained clinical attention in the 1980s and were named Syndrome of Irreversible Lithium-Effectuated Neurotoxicity (SILENT). The authors review the published cases of SILENT reported in the literature and discuss various clinical manifestations.

Methods: The authors' inclusion criteria included persistence of sequelae for at least 2 months after the cessation of lithium administration. They conducted a MEDLINE and Pub Med search for journal articles from the year 1965 to 2004. They also cross-referenced available papers.

Results: The authors identified 90 cases of SILENT in peer-reviewed publications. Persistent cerebellar dysfunction was the most commonly reported sequela. Other atypical presentations have also been reported.

Conclusion: Although the biologic mechanism remains unclear, the authors hypothesize that the putative cause of SILENT is demyelination caused by lithium at multiple sites in the nervous system, including the cerebellum. Recent advances in the understanding of the molecular basis of lithium-induced neurotoxicity may be able to provide a means of defining a pathway associated with the long-term prophylactic properties of lithium, distinct from its toxicity profile. This identification of differential gene expression patterns that distinguish between therapeutic and toxic actions of lithium may help in the discovery of new drugs for mood stabilization. Clinically and heuristically, it is important to raise the awareness of this syndrome so that clinicians are able to avoid it. A precise definition, operational diagnostic criteria, and a descriptive name will aid in the early identification and prevention of SILENT.

Publication types

  • Review

MeSH terms

  • Adult
  • Aged
  • Female
  • Humans
  • Lithium / adverse effects*
  • Male
  • Middle Aged
  • Neurotoxicity Syndromes / diagnosis
  • Neurotoxicity Syndromes / etiology*
  • Neurotoxicity Syndromes / pathology
  • Neurotoxicity Syndromes / psychology*
  • Syndrome


  • Lithium