Lithium, Electroconvulsive Therapy and Cognition: A Systematic Review and Meta-Analysis.

OBJECTIVE

We aimed to synthesize the evidence on confusional states and neurocognitive changes associated with the concurrent use of lithium and electroconvulsive therapy (ECT).

METHODS

We conducted a systematic search of PubMed, EMBASE, Web of Science, Scopus, Cochrane Library, CINAHL, PsycArticles, and clinical trials registries up to September 2025. Eligible studies compared the incidence of confusional states or changes in neurocognitive test scores in patients receiving lithium and ECT (Li-ECT) and those receiving ECT without lithium. We performed separate meta-analyses and calculated odds ratios (OR) with 95% confidence intervals (CI) for dichotomous outcomes and standardized mean differences (SMD) for continuous outcomes. Additionally, case reports describing cognitive effects of Li-ECT were synthesized.

RESULTS

Sixteen studies were included: 11 studies (n = 66,156) assessed confusional states and five (n = 341) evaluated neurocognitive changes. The Restricted Maximum-Likelihood meta-analysis showed no significant association between lithium use and confusional states (OR 2.09; 95% CI: 0.94-4.66; p = 0.07), whereas a Paule-Mandel sensitivity analysis suggested a significant association (OR 2.38; 95% CI: 1.20-4.74; p = 0.01). No significant differences were observed in changes in global cognitive functioning, autobiographical memory or verbal fluency test scores ([SMD = 0.25; 95% CI: -0.98-1.49; p = 0.69], [SMD = 0.27; 95% CI: -1.37; 1.9; p = 0.75], [SMD = -0.89; 95% CI: -3.18; 1.39; p = 0.44]).

CONCLUSION

Current evidence does not show a significant increase in cognitive side effects associated with lithium use during ECT. However, methodological limitations, sensitivity to meta-analytic assumptions and clinical heterogeneity preclude definitive conclusions. Large prospective studies using standardized cognitive assessments are needed to confirm the tolerability of concurrent lithium and ECT use. While our findings support the cautious continuation of lithium during ECT, individualized clinical decision-making remains crucial to maximize efficacy and minimize cognitive burden.