Goodbye to Compounded Analgesic Creams

by Drew Rosielle (@drosielle)

Annals of Internal Medicine has just published one of the better trials of compounded analgesic creams I've yet to see, and unfortunately it's pretty damning.

It's a randomized, double-blind, placebo-vehicle controlled, intention-to-treat, 3 parallel armed study of 3 different compounded creams for adult patients (median age ~50 years, ~50% women) with localized chronic pain (the 3 groups had neuropathic, nociceptive, or mixed pain syndromes). It took place at Walter Reed. Each arm had about 130 subjects (which, for this type of research, and compared to many other investigations of compounded creams, is quite a lot). Patients needed to have chronic pain (longer than 6 weeks), rated at least 4/10, and localized to a body area or two extremities. Broadly speaking about half the subjects' pain was incited by an injury or surgery. Pain was classified as nociceptive vs neuropathic vs mixed based on a pain physician's assessment, more or less. About 20% of patients were on systemic opioids.

Subjects were prescribed one of 3 compounded creams (or the placebo/vehicle cream which was PLO) and asked to apply it to their painful region three times a day:

• Neuropathic: 10% ketamine, 6% gabapentin, 0.2% clonidine, and 2% lidocaine
• Nociceptive: 10% ketoprofen, 2% baclofen, 2% cyclobenzaprine, and 2% lidocaine
• Mixed: 10% ketamine, 6% gabapentin, 3% diclofenac, 2% baclofen, 2% cyclobenzaprine, 2% lidocaine

The primary outcome was average pain score after 1 month of treatment. They presented several prespecified secondary outcomes too. The study had 90% power to detect a pain reduction of 1.2 (out of 10) points with 60 patients per treatment arm, which they met.

Basically there weren't any statistically, let alone clinically, meaningful differences between the groups, regardless of pain type. For all groups, pain was reduced at a month by around 1-1.4/10 points on the 0-10 NRS, regardless of receiving active drug or placebo cream. Secondary outcomes including patient judgement of a positive outcome (ie, the percent of patients who reported they considered the cream a success) were the same between all the groups too (around 20%). Health related quality of life did not differ either between groups at a month.



This study is one of the largest and best-designed study I'm aware of of these creams, and the findings are pretty clear: such creams benefit patients via placebo mechanisms, aka they don't work.

Note that there is a separate body of research on some other topicals which should not be confused with this study. Eg, the 5% lidocaine patch for post-herpetic neuralgia, topical capsaicin for a variety of neuropathies, and at least some topical NSAIDs for osteoarthritis, and topical opioids. I'm not broadly endorsing those either - it's complicated - however they weren't tested here and the take home point is we should stop making our patients pay exorbitant out of pocket costs for these compounded analgesic placebos, not necessarily those others.

Particularly for painful axonal neuropathies, many of us struggle with how to control those adequately, especially chemotherapy induced ones which don't respond well to most systemic drugs, and I've ordered plenty of fancy creams in the past for my patients, most of whom paid out of pocket for them, and I think it's time to stop doing that.

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Drew Rosielle, MD is a palliative care physician at the University of Minnesota Health in Minnesota. He founded Pallimed in 2005. You can occasionally find him on Twitter at @drosielle.

References

1 Brutcher RE, Kurihara C, Bicket MC, Moussavian-Yousefi P, Reece DE, Solomon LM, et al. "Compounded Topical Pain Creams to Treat Localized Chronic Pain: A Randomized Controlled Trial." Ann Intern Med. [Epub ahead of print ] doi: 10.7326/M18-2736