An overall lack of quality evidence exists for the use of topical analgesics and anesthetics (creams, gels, and patches) as a therapeutic method for treating chronic pain, according to a new review published in the journal Dermatitis.

The review examined the most common medications – eight in total – that are used in topical compounds for pain and their mechanisms, adverse effects, and evidence of efficacy. Typically, compounded topical medications have three or more medications incorporated into a base that enhances epidermal penetration.

Analysis of case studies found that ketamine 1% as a topical agent was not effective in patients with neuropathic pain. However, in open studies the therapeutic effects seemed to strengthen with repeated application. The researchers found topical gabapentin has been empirically used off-label as a single agent or in combination with amitriptyline for neuropathic pain. A retrospective study found some benefit of topical gabapentin in vulvodynia. 

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Off-label use with topical clonidine, a lipophilic, can reduce hypersensitivity in inflammatory nerve injury depending on the nociceptors in the skin. It can relieve hyperalgesia, and studies have shown transdermal patches can provide some relief in sympathetically maintained pain and diabetic neuropathy.

Topical baclofen (containing also amitriptyline and ketamine) was shown in one double-blind randomized trial to significantly improved both sensory (P=0.053) and motor subscales (P=0.021) over the placebo to alleviate neuropathic pain, numbness, and tingling of chemotherapy-induced peripheral neuropathy. The greatest benefit was displayed in relief of tingling, cramping, and shooting/burning pain in the hands.

Topical NSAIDS were found to provide good levels of pain relief in a Cochrane database review, without significant systemic adverse events.

For most treatments reviewed, the application of topical compounds was considered an off-label use. Most commonly reported adverse events from topical pain medications were allergic contact dermatitis (ACD) and most reports described these reactions as mild and transient. Customized patch testing is a valuable tool in determining the offending allergen.

The authors of the review highlight the benefits provided by topical analgesics: ease of application, decreased adverse events and drug-drug interactions for patients with neuropathic and other chronic pains. The overall quality of evidence is lacking and research data often conflicts, noted the authors. Nevertheless, “as compounded topical analgesics increase in prevalence it is important that clinicians and patients have a better understanding of how these medications work,” the study concludes.

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