Grand Rounds

Do Compounded Analgesic Creams Alleviate Chronic Pain?

BACKGROUND AND PURPOSE:

Topical creams to reduce chronic pain are commonly used
There is evidence to support the use of topical NSAIDs, capsaicin and lidocaine but data for other topical pain creams remains limited
- A recent Cochrane review found topical NSAIDs only helpful for knee osteoarthritis
CMS (Medicaid/Medicare) spent >$500,000,000 on topical compounded pain creams in 2015, resulting in a call for an assessment of prescribing practices and effectiveness
- Department of Defense spent approximately $6,000,000 per day
Brutcher et al. (Annals of Internal Medicine, 2019) assessed the efficacy of compounded creams for chronic pain

Randomized, double-blind controlled trial
Three types of chronic pain were included
- neuropathic
- nociceptive (nonneuropathic)
- mixed
Patients received either
- Pain creams compounded for neuropathic pain (ketamine, gabapentin, clonidine, and lidocaine)
- Nociceptive pain (ketoprofen, baclofen, cyclobenzaprine, and lidocaine)
- Mixed pain (ketamine, gabapentin, diclofenac, baclofen, cyclobenzaprine, and lidocaine)
- Placebo
Cream applied to affected areas 3 times per day
Primary outcome measure: Average pain score at 1 month after treatment
- Positive categorical response was a reduction in pain score of ≥2 plus a score >3 on a 5-point satisfaction scale
Secondary outcomes included
- Short Form-36 Health Survey score | Satisfaction | Categorical response

133 people were included in each pain type group
Primary outcome: No differences were found in the mean reduction in average pain scores between the treatment and control groups
- Neuropathic pain: −0.1 points (95% CI, −0.8 to 0.5 points)
- Nociceptive pain: −0.3 points (CI, −0.9 to 0.2 points)
- Mixed pain: −0.3 points (CI, −0.9 to 0.2 points)
- All patients: −0.3 points (CI, −0.6 to 0.1 points)
At 1 month, positive outcomes were observed in all groups
- Treatment groups: 36%
- Control group: 28%
- Risk difference: 8% (95% CI, −1% to 17%)
Side effects were similar between all groups, with no serious adverse events
- Irritation was higher in the treatment groups vs placebo (7% vs 2%)

While acknowledging short follow-up, the authors conclude that topical compounded pain creams are not superior to placebo in the management of chronic pain
No significant differences were observed in
- Pain scores | Functional improvement | Satisfaction
Many of the drugs found in compounded pain medications are ligands for CNS receptors and may not reach active sites via transdermal application
NSAIDs and lidocaine included in these compounds may not exert their effect due to dilution in the overall compounded cream

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