Risk of Valproic Acid-Related Tremor: A Systematic Review and Meta-Analysis

Purpose: To evaluate the incidence and risk of tremor in patients treated with valproic aid (VPA) monotherapy. Methods: We searched the PubMed, Embase, and Cochrane Library databases to gather relevant data on tremor in patients taking VPA and other drugs and performed a meta-analysis using Stata15.1 software. Results: Twenty-nine randomized controlled trials (RCTs) met the inclusion criteria and were included in the meta-analysis. The overall incidence of tremor in patients receiving VPA therapy was 14% [OR = 0.14, 95% CI (0.10–0.17)]. The pooled estimate risk of tremor showed a significant difference between patients treated with VPA and all other drugs [OR = 5.40, 95% CI (3.22–9.08)], other antiepileptic drugs (AEDs) [OR = 5.78, 95% CI (3.18–10.50)], and other non-AEDs [OR = 4.77, 95% CI (1.55–14.72)]. Both a dose of <1,500 mg/d of VPA [included 500 mg/d: OR = 3.57, 95% CI (1.24–10.26), 500–999 mg/d: OR = 3.99, 95% CI (1.95–8.20), 1,000–1,499 mg/d: OR = 8.82, 95% CI (3.25–23.94)] and a VPA treatment duration of <12 m [included ≤ 3 months: OR = 3.06, 95% CI (1.16–8.09), 3–6 months: OR = 16.98, 95% CI (9.14–31.57), and 6–12 months: OR = 4.15, 95% CI (2.74–6.29)] led to a higher risk of tremor than did other drugs, as did higher doses and longer treatment times. Conclusion: Compared with other drugs, VPA led to a higher risk of tremor, and the level of risk was associated with the dose and duration of treatment.