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

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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 ‘thera-
peutic’ 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 disor-
ders. We urge future examinations of LDL’s potential to prevent cognitive/affective syndromes
Original languageEnglish
Article number104975
JournalNeuroscience and Biobehavioral Reviews
Publication statusPublished - Jan 2023


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


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