Clonidine

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Clonidine is an α2-adrenergic receptor agonist originally used to treat hypertension.

Chronic Pain

Alpha-2 receptors are also found on nociceptors of the epidermis. Activation of these reeptors lead to release of an inhibitory G-protein which leads to several downstream effects involved in the initiation and maintnenace of abnormal nociceptor excitability.

A few possible mechanisms for the analgesic effect of clonidine has been proposed, however no effect has been found on experimental pain in health subjects.

• α2-agonist on receptors in the dorsal horn.
• Noradrenergic effects enhancing descending pain inhibition
• Enhanced parasympathetic function leading to lower pain perception
• Reduced anxiety

In some patients with peripheral neuropathic pain the small fibres are severely denervated and so clonidine is unlikely to work.

A double blind RCT (n=179) showed that you can predict the response to topical clonidine 0.1% applied twice daily by first applying capsaicin 0.1% to a 1cm diameter area of skin of the pretibial area midway between the calf and ankle of both legs. An occlusive dressing is applied and the cream is left in place for 30 minutes.

Clonidine did not work in patients who did not detect capsaicin (pain of 0). In those with a pain response, clonidine was more effective than placebo, which was more pronounced with increasing pain ratings to capsaicin. In those with pain of 2 or more to capsaicin, clonidine had a 2.6 mean reduction in pain compared to 1.4 for placebo. Those who reported relief also had greater intraepidermal nerve fibre densities on biopsy. It takes minimum 6 weeks for the full effect. The NNT was approximately 5 for 30% pain relief in those with pain rating of 2 or more to capsaicin.

The clonidine bottles contained 0.1% clonidine and dispensed 0.65 g of gel (0.65 mg clonidine) per dose. The total daily clonidine dose was 3.9 mg (2 feet, 3 times/day; 0.65 mg x 6)

We do not have topical clonidine in New Zealand. The clonidine patches contain 2.52mg for the 0.1mg/day patch, 5.04mg for the 0.2mg/day patch, and 7.56mg for the 0.3mg/day patch.

Opioid Withdrawal

Clonidine can be used to reduce autonomic hyperactivity in opioid withdrawal. The dose is 25-150mcg three times daily, adjusted according to response for up to 3 days. Then reduce by a quarter of third day's dose over the next 3 days and as withdrawal symptoms subside. Withhold dose if blood pressure is below 100/60 or heart rate below 60.

Side Effects

Skin irritation is common with clonidine patches. The risk can be reduced by avoiding hard soaps, applying a lipid-rich moisturiser several hours before applying the patch, gently cleaning the residual adhesive after removing the patch, and rotating the site. If persistent then trial steroid ointment before applying the patch.