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

Area of Science:

• Neuroscience and Psychiatry
• Clinical Pharmacology
• Evidence Synthesis and Meta-Analysis

Background:

• Lithium is a mood stabilizer commonly used in psychiatric practice.
• Electroconvulsive therapy (ECT) is an effective treatment for severe mental illnesses.
• The concurrent use of lithium and ECT (Li-ECT) raises concerns regarding potential cognitive side effects.

Purpose of the Study:

• To systematically synthesize existing evidence on confusional states and neurocognitive changes associated with Li-ECT.
• To compare the incidence of cognitive side effects in patients receiving Li-ECT versus ECT alone.
• To inform clinical decision-making regarding the safety of combined Li-ECT treatment.

Main Methods:

• Systematic literature search across multiple databases (PubMed, EMBASE, Web of Science, Scopus, Cochrane Library, CINAHL, PsycArticles) and clinical trials registries up to September 2025.
• Meta-analysis of dichotomous (confusional states) and continuous (neurocognitive test scores) outcomes using Restricted Maximum-Likelihood and Paule-Mandel methods.
• Synthesis of case reports detailing cognitive effects of Li-ECT.

Main Results:

• Analysis of 16 studies (11 on confusional states, 5 on neurocognitive changes) involving over 66,000 patients.
• No significant association between lithium use and confusional states in the primary meta-analysis (OR 2.09; p=0.07), though a sensitivity analysis suggested significance (OR 2.38; p=0.01).
• No significant differences observed in changes in global cognitive functioning, autobiographical memory, or verbal fluency between Li-ECT and ECT alone.

Conclusions:

• Current evidence does not demonstrate a significant increase in cognitive side effects with concurrent lithium and ECT use.
• Methodological limitations and clinical heterogeneity necessitate caution and preclude definitive conclusions.
• Large prospective studies with standardized assessments are required; individualized decision-making remains critical.