Objective: To evaluate the efficacy of Clonidine in reducing tic severity and improving global clinical outcomes in patients with Tourette syndrome.

Background: Tourette syndrome is a neurodevelopmental disorder of motor and vocal tics that is usually managed with dopamine antagonists like haloperidol, despite their severe side effects. Clonidine, an α2-adrenergic agonist, is a common alternative whose efficacy is debatable.

Method: A search of PubMed, Scopus, and Embase was done to find randomized controlled trials (RCTs) assessing Clonidine for Tourette syndrome. The Yale Global Tic Severity Scale (YGTSS) was used to measure the primary outcome: a decrease in tic severity. As a secondary outcome, the Clinical Global Impression (CGI) Scale was investigated. ROB2 was used to evaluate the risk of bias, and a random-effects model was used to consider variability. I2 was used to quantify heterogeneity and sensitivity analysis was conducted to investigate potential variability sources.

Results: The inclusion criteria were met by 7 RCTs with 1,298 participants. With significant variations between control groups, Clonidine showed a statistically significant decrease in tic severity as compared to controls (MD = 11.09 [0.96, 21.23], p = 0.03). Trials comparing clonidine to haloperidol had the strongest effect (MD = 21.42 [19.45, 23.39], I2 = 60%), but studies using a placebo had a less noticeable effect (MD = 3.30 [-1.94, 8.55], I2 = 80%) [Figure 1]. A consistent improvement in overall clinical status across trials was indicated by the statistically significant improvement in CGI ratings that Clonidine brought about (MD = -0.32 [−0.55, −0.10], p = 0.005), with no heterogeneity (I2 = 0%). [Figure 2]

Significant heterogeneity in tic severity remained even after subgrouping, most likely due to differences in trial populations, dosage schedules, and control treatments. When excluding haloperidol trials from sensitivity analysis, I2 dropped to 70%, suggesting that these studies significantly increased variability.

Conclusion: This meta-analysis provides strong evidence that clonidine reduces tic severity and improves clinical outcomes, especially compared to haloperidol. However, substantial heterogeneity limits generalizability, underscoring the need for high-quality trials to refine treatment recommendations, optimize dosing, and assess long-term safety.

[Figure1]: YGTSS SCALE (REDUCTION RATE)

[Figure2]: CGI-C scale

References: [1] J. F. Leckman, M.doi Hardin, M. A. Riddle, J. Stevenson, S. I. Ort, and D. J. Cohen, “Clonidine treatment of Gilles de la Tourette’s syndrome,” Arch Gen Psychiatry, vol. 48, no. 4, pp. 324–328, 1991, doi: 10.1001/ARCHPSYC.1991.01810280040006.
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[5] Y. S. Du et al., “Randomized double-blind multicentre placebo-controlled clinical trial of the clonidine adhesive patch for the treatment of tic disorders,” Aust N Z J Psychiatry, vol. 42, no. 9, pp. 807–813, 2008, doi: 10.1080/00048670802277222.
[6] E. F. Hedderick, C. M. Morris, and H. S. Singer, “Double-blind, crossover study of clonidine and levetiracetam in Tourette syndrome,” Pediatr Neurol, vol. 40, no. 6, pp. 420–425, Jun. 2009, doi: 10.1016/J.PEDIATRNEUROL.2008.12.014.
[7] Z. Zhao et al., “Efficacy of Clonidine Adhesive Patch for Patients With Tourette Syndrome: A Randomized, Double-blind, Placebo-Controlled, Multicenter Clinical Trial,” Clin Neuropharmacol, vol. 47, no. 5, Sep. 2024, doi: 10.1097/WNF.0000000000000605.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/efficacy-of-clonidine-for-tourette-syndrome-an-updated-meta-analysis-of-randomized-controlled-trials/