The effects of lithium on cognition in humans: A systematic review

Abstract

Background: Lithium, a mainstay treatment for bipolar disorders, has shown promise in treating cognitive impairments. However, concerns about cognition-related side effects persist. Aims: We aimed to synthesise the evidence on how lithium affects cognition by comparing cognitive performance before and after starting lithium treatment. Methods: A systematic search was conducted to identify studies examining lithium’s effects on cognition. The review considered studies with adult human participants that reported quantitative cognitive outcomes using within-subject comparisons between lithium-absent and lithium-present conditions. Results: Thirty-two articles describing 30 studies were included (727 participants, approximately 54% female, mean age ± 50 years old). The studies exhibited significant heterogeneity within cognitive domains, including global cognition (15 studies), memory (19 studies), processing and psychomotor speed (8 studies), attention (9 studies), verbal fluency (4 studies) and executive function (6 studies). The included studies comprised 16 randomised controlled trials (RCTs) and 14 non-RCTs, with study populations ranging from individuals with affective disorders (13 studies) to neurocognitive disorders (11 studies) and healthy individuals (6 studies). Some studies reported cognitive enhancements, particularly in individuals with affective disorders, while others documented declines or mixed results. Conclusions: Definitive conclusions regarding lithium’s isolated cognitive effects remain elusive, particularly considering the influence of factors such as affective state, population and methodological heterogeneity among studies. Further research is needed to conclusively determine the raw cognitive impacts of lithium therapy, requiring larger RCTs across distinct populations. Prioritising the resolution of main symptoms should remain the primary therapeutic goal of lithium treatment.