Safety and efficacy of lithium in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis of randomized controlled trials

Objectives: This study provides a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating the safety and efficacy of lithium in amyotrophic lateral sclerosis (ALS) patients.

Methods: PubMed, Web of Science, Cochrane CENTRAL, Scopus, and Your Journals@Ovid were searched up to 9 December 2022. RCTs investigating lithium, either alone or with any supplement, in ALS patients were included. Meta-analysis was performed using RevMan and results are presented in forest plot.

Results: Four RCTs with 469 patients met the inclusion criteria and were included in our study. Lithium doses varied among the included studies and one study used a combined therapy of lithium with valproate. Meta-analysis showed no difference between lithium and placebo regarding severe adverse events (odds ratio = 1.13, 95% confidence interval: 0.73 to 1.75, P = 0.58). No significant differences were observed with regard to survival rate between the two groups (hazard ratio = 0.95, 95% confidence interval: 0.65 to 1.37, P = 0.77). There were also no significant differences between the two groups with regard to average changes of revised amyotrophic lateral sclerosis functional rating scale (P = 0.35) and forced vital capacity percentage predicted (P = 0.73). Subgroup analysis showed no significant differences regarding all investigated outcomes either for lithium alone or lithium with valproate.

Conclusion: Current evidence suggests a safety profile with no benefit of lithium for ALS. However, given the limited number of RCTs and the safety findings, we recommend further well-designed RCTs to investigate lithium and valproate in ALS patients.