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

To evaluate the incidence and risk of tremor in patients treated with valproic aid (VPA) monotherapy. 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. 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. 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.