Identifying the neuropsychiatric health effects of low-dose lithium interventions: A systematic review

Neurosci Biobehav Rev. 2023 Jan:144:104975. doi: 10.1016/j.neubiorev.2022.104975. Epub 2022 Nov 24.


Background: Lithium is widely evidenced for its neuropsychiatric benefits. Advantages of 'sub-therapeutic' doses are increasingly being reported, which is apposite given enduring concerns around adverse effects of 'therapeutic' doses. We aimed to synthesise all available evidence from interventional studies investigating low-dose lithium (LDL) across neuropsychiatric outcomes.

Methods: Electronic databases were systematically searched to include studies where a group of adult humans were treated with LDL (∼serum level ≤0.6 mmol/L), where data describing a neuropsychiatric outcome were reported either before and after treatment, and/or between lithium and a comparator.

Results: 18 articles were examined and grouped according to outcome domain (cognition, depression, mania, and related constructs e.g., suicidality). Significant benefits (versus placebo) were identified for attenuating cognitive decline, and potentially as an adjunctive therapy for people with depression/mania. Across studies, LDL was reported to be safe.

Conclusions: Despite the paucity and heterogeneity of studies, LDL's apparent pro-cognitive effects and positive safety profile open promising avenues in the fields of neurodegeneration, and augmentation in affective disorders. We urge future examinations of LDL's potential to prevent cognitive/affective syndromes.

Keywords: Affect; Cognition; Depression; Lithium; Low-dose; Mania; Microdose; Systematic review.

Publication types

  • Systematic Review
  • Review
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Antipsychotic Agents* / therapeutic use
  • Humans
  • Lithium* / therapeutic use
  • Mania / chemically induced
  • Mania / drug therapy
  • Mood Disorders / drug therapy


  • Lithium
  • Antipsychotic Agents