Modest Beneficial Effects With Topical Clonidine for Painful Diabetic Neuropathy

This Cochrane review aimed to assess the analgesic efficacy of topical clonidine for adults with chronic neuropathic pain.

An updated systematic review and meta-analysis published in Cochrane Database of Systematic Reviews validated previous reports that some patients with painful diabetic neuropathy (PDN) benefited from topical clonidine (TC) treatment.

Investigators from Jagiellonian University Collegium Medicum in Poland searched publication databases through October 2021 for randomized, double-blind studies of TC for the treatment of PDN. The primary outcomes were patient-reported pain relief of ≥50% or ≥30% and improvement on the Patient Global Impression of Change (PGIC) scale.

This review included the 2 studies included in the original review published in 2015 and 2 additional studies, together comprising 743 patients with PDN. Patients were instructed to apply 0.1% or 0.2% TC, placebo, or active comparator 2 to 3 times daily to the painful area for 8 to 12 weeks.

Compared with placebo, TC was favored for patient-reported relief of ≥30% (risk ratio [RR], 1.35; 95% CI, 1.03-1.77).

TC was not favored for patient-reported relief of ≥50% (relative risk [RR], 1.21; 95% CI, 0.78-1.86), much or very much improved PGIC (RR, 1.06; 95% CI, 0.76-1.49), or very much improved PGIC (RR, 1.82; 95% CI, 0.89-3.72).

No effects were observed for withdrawal due to adverse events (RR, 0.34; 95% CI, 0.04-3.18), experiencing 1 or more adverse event (RR, 0.65; 95% CI, 0.14-3.05), or withdrawal due to lack of efficacy (RR, 1.01; 95% CI, 0.06-15.92).

Compared with an active comparator, TC tended to be favored for participant-reported pain relief of ≥50% (RR, 1.41; 95% CI, 0.99-2.0).

All studies included in this analysis had unclear or high risk for bias in most risk domains.

This study found that TC use among patients with PDN was associated with ≥30% improvement in pain for some, however, there was little evidence to suggest that TC was associated with additional benefits.

Together these findings indicate that for every 8 patients treated, 1 would achieve a moderate benefit with TC compared with placebo.


Serednicki WT, Wrzosek A, Woron J, et al. Topical clonidine for neuropathic pain in adults. Cochrane Database Syst Rev. 2022;5(5):CD010967. doi:10.1002/14651858.CD010967.pub3