From the Journals

Compounded pain creams no better than placebo creams in localized chronic pain



Specially formulated topical pain creams are no better than placebo creams for relieving localized chronic pain, according to results from a double-blind, randomized, placebo-controlled trial.

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Study authors led by Robert E. Brutcher, PharmD, PhD, of Walter Reed National Military Medical Center in Bethesda, Md., said their findings published Feb. 4 in Annals of Internal Medicine suggest compounded pain creams should not be routinely used for chronic pain conditions.

The researchers noted that the use of compounded topical pain creams has increased dramatically despite “weak evidence” supporting their efficacy to treat localized pain, and this is particularly the case in military personnel, where the authors said treatments without central effect may be particularly beneficial because “opioid therapy may render a service member nondeployable and medications that affect the central nervous system may have a negative effect on judgment and motor skills.”

They noted a report from the U.S. Government Accountability Office that showed Tricare’s pharmacy benefits program paid $259 million for compounded medications in the 2013 fiscal year, a figure that increased to $746 million in 2014.

“The soaring costs, coupled with sparse efficacy data prompted the Defense Health Agency to evaluate this issue,” they wrote.

The objectives of the current study were to assess the efficacy of compounded pain creams for chronic pain conditions and determine whether efficacy differed for the various pain classifications.

“We hypothesized that, compared with placebo, compounded topical pain creams would provide greater pain relief and functional improvement,” they said.

The randomized trial involved 133 patients diagnosed with neuropathic pain, 133 with nociceptive pain, and 133 with mixed pain who had attended pain clinics at Walter Reed. Patients were aged between 18 and 90 years and had localized pain in the face, back or buttocks, neck, abdomen, chest, groin, or in up to two extremities. To be included in the study, they were also required to have an average pain score of 4 or greater on a 0- to 10-point numerical rating scale during the preceding week and have symptoms lasting longer than 6 weeks.

Patients in all three pain subgroups were randomized in a 1:1 ratio to receive either a compounded pain cream or a placebo cream. The authors noted that their “pain cream formulations were selected on the basis of accepted systemic indications for neuropathic and nociceptive pain.”

The formulation given to participants with neuropathic pain (n = 68) contained 10% ketamine, 6% gabapentin, 0.2% clonidine, and 2% lidocaine. The patients with nociceptive pain (n = 66) received a cream with 10% ketoprofen, 2% baclofen, 2% cyclobenzaprine, and 2% lidocaine. Those with mixed pain (n = 68) were given a cream containing 10% ketamine, 6% gabapentin, 3% diclofenac, 2% baclofen, 2% cyclobenzaprine, and 2% lidocaine. The authors said the concentrations of individual medications were based on previous trials that evaluated topical use.

The patients, who had a mean age across the groups that ranged from 48 to 57 years, applied cream to affected areas three times per day, with the amount dispensed determined by the size of the area experiencing pain. About half of the patients were women.

The primary outcome measures were an average pain score 1 month after treatment. A positive categorical response was a reduction in pain score of 2 or more points coupled with a score above 3 on a 5-point satisfaction scale. Secondary outcomes included Short Form-36 Health Survey scores, satisfaction, and categorical response. Participants with a positive outcome were followed to 3 months.

Change in the primary outcome of average pain score at 1 month did not differ between the active cream and placebo groups for any type of pain classification. The change was only –0.1 points (95% confidence interval, –0.8 to 0.5 points) for neuropathic pain, –0.3 points (95% CI, –0.9 to 0.2 points) for nociceptive pain, and –0.3 points (95% CI, –0.9 to 0.2 points) for mixed pain.

Among all patients combined, an overall change in average pain scores of –0.3 points (95% CI, –0.6 to 0.1 points) that favored the active-ingredient cream also did not differ between the treatment and placebo groups.

“The lower 95% confidence bounds for the 1-month between-group differences were all 0.9 points or less and excluded clinically meaningful benefits with the compounded topical pain cream,” the authors wrote.

Secondary outcomes also did not differ between the two study groups for any type of pain classification or for the entire cohort.

“Although participants in both treatment and control groups had improvement in their pain throughout the study, no significant differences were observed in pain scores, functional improvement, or satisfaction in the cohort or in any subgroup,” the authors concluded.

They noted that their findings were consistent with previous studies that also showed a lack of efficacy for most topical pain creams.

While some randomized trials have suggested positive findings for capsaicin, lidocaine, and NSAIDs, the authors noted that they did not find a similar benefit in their study population.

“Administered as stand-alone agents, lidocaine and NSAIDs may alleviate pain, although the effect size is small and the number needed to treat is large,” they wrote.

“Considering the increased costs of using a non–FDA-approved and regulated compounded cream rather than a single agent, we caution against routine use of compounded creams for chronic pain,” they wrote.

They noted that their study had several limitations, including that conventional treatments had failed in some of the participants before they enrolled in the study, increasing the likelihood that subsequent therapy would not be effective.

The authors suggested that future studies should aim to establish whether targeting specific types of pain or adding other agents like dimethyl sulfoxide would result in better outcomes.

The Centers for Rehabilitation Sciences Research in the U.S. Department of Defense’s Defense Health Agency funded the study. Two authors reported receiving grants and personal fees from several pharmaceutical companies.

SOURCE: Brutcher RE et al. Ann Intern Med. 2019 Feb 4. doi: 10.7326/M18-2736.

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