Efficacy and safety of clonidine adhesive patch in the treatment of children with tic disorders: a systematic review and meta-analysis of randomized controlled trials

Tic disorders (TD) are common neuropsychiatric disorders that predominantly affect children. Although antipsychotic medications such as tiapride and haloperidol are widely used in clinical practice, their use may be limited by adverse effects. The clonidine adhesive patch, a transdermal α2-adrenergic agonist, may present a potential better-tolerated therapeutic option compared with oral medications. This systematic review and meta-analysis evaluated the efficacy and safety of the clonidine adhesive patch in children with TD. A systematic search of PubMed, Web of Science, the Cochrane Library, WanFang Data, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and SinoMed was conducted to identify randomized controlled trials (RCTs) published from database inception to September 1, 2025. Study quality was assessed according to the Cochrane Handbook for Systematic Reviews of Interventions. Fourteen RCTs involving 1609 children were included in this meta-analysis. Compared with conventional oral anti-tic medications, clonidine adhesive patch monotherapy was associated with a higher clinical response rate than haloperidol (OR = 2.01; 95%CI: 1.38–2.93, P = 0.0003, I² = 0%), and greater reductions in Yale Global Tic Severity Scale (YGTSS) scores (MD = 21.94; 95%CI: 21.03–22.86, P < 0.00001, I² = 0%). It was also associated with a higher clinical response than tiapride (OR = 1.71; 95%CI: 1.01–2.88, P = 0.05, I² = 31%). Combination therapy with the clonidine adhesive patch plus tiapride was associated with higher clinical response rate than tiapride monotherapy (OR = 2.02; 95%CI: 1.03–3.98, P = 0.04, I² = 30%). The incidence of adverse events was lower with clonidine adhesive patch than with haloperidol (OR = 0.19; 95%CI: 0.11–0.33, P<0.00001, I² = 0%) or tiapride (OR = 0.48; 95%CI: 0.24–0.94, P = 0.03, I² = 10%). No statistically significant difference in adverse events was observed between the clonidine adhesive patch plus tiapride and tiapride monotherapy (OR = 0.63; 95%CI: 0.12–3.34, P = 0.58, I² = 76%). Three additional RCTs used unique comparators (placebo, Vitamin D3, and haloperidol plus clonidine adhesive patch), precluding quantitative synthesis because each comparison was represented by a single study. These findings were therefore summarized descriptively. Current evidence suggests that clonidine adhesive patch may have potential therapeutic benefits for pediatric TD, with possible advantages in clinical response and tolerability compared with some conventional oral anti-tic medications. However, the certainty of the available evidence remains limited due to methodological limitations and heterogeneity among studies. Further large-scale, high-quality, placebo-controlled RCTs are required to confirm the efficacy and long-term safety of clonidine adhesive patch in children with TD. Not applicable.