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

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Article number104975
JournalNeuroscience and Biobehavioral Reviews
PublishedJan 2023

Bibliographical note

Funding Information: This paper represents independent research funded by the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London . The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The authors note that the content of this manuscript has not been published or submitted for publication elsewhere. Publisher Copyright: © 2022 The Authors

King's Authors


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

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