Background: Valproic acid (VPA) is widely used in neurological and psychiatric disorders. Emerging evidence suggests its association with thyroid dysfunction, particularly subclinical hypothyroidism (SCH), though reported prevalence varies. Objective:To estimate the pooled prevalence of subclinical hypothyroidism in patients receiving valproic acid therapy. Methods: A systematic review and meta-analysis of observational studies were conducted in accordance with PRISMA guidelines. PubMed, Scopus, and Web of Science were searched up to January 2025. Studies reporting the prevalence of SCH in patients on VPA were included. A random-effects meta-analysis was used to calculate the pooled prevalence with 95% confidence intervals (CIs). Results: A total of 22 studies (n = 2,845 patients)were included. The pooled prevalence of SCH among VPA users was18.7% (95% CI: 14.2–23.9%). Subgroup analysis showed a higher prevalence in pediatric populations (23.5%) compared to adults (12.1%). Heterogeneity was moderate (I² = 58%). The funnel plot suggested minimal publication bias. Conclusion: Valproic acid therapy is associated with a significant prevalence of subclinical hypothyroidism, particularly in pediatric populations. Routine thyroid function monitoring is recommended.
Thomas et al. (Wed,) studied this question.