BALTIMORE, MD – Extremely high payouts from federal health insurance plans for prescription topical pain creams or gels led Congress to mandate a study on the effectiveness of the products.
The new study published in Annals of Internal Medicine reports that no statistically significant difference was determined between pain relief from those products vs. placebo.
The investigation was launched after TRICARE, the government-managed health insurance plan covering some active duty and retired military personnel and their family members, reported it spent $259 million on compounded topical pain creams in fiscal year 2013, with the cost increasing to $746 million in 2014. In fact, for the first month of 2015, the DoD reported it spent about $6 million per day on the medications.
At the same time, the Medicare Part D program paid out more than half a billion dollars for the creams in 2015.
“Our study of nearly 400 pain patients suggests that people who use these compounded creams and gels are being taken advantage of, because the scientific evidence to support a benefit is not there,” explained senior author Steven P. Cohen, MD, professor of anesthesiology and critical care medicine, neurology, and physical medicine and rehabilitation at the Johns Hopkins University School of Medicine, and director of pain research at Walter Reed National Military Medical Center.
The products are popular, Cohen noted, because they appear to be a safer way to get pain relief without the risks or side effects of potentially addictive or dangerous drugs that are usually given orally or by injection. The compounded creams and gels generally contain one or more prescription or other anesthetic, analgesic, sedative, antidepressant, anti-seizure or muscle relaxant drugs that are used to treat pain.
To determine effectiveness, researchers conducted randomized controlled trials involving 399 military treatment facility patients with localized pain classified by each patient’s treating physician as either neuropathic, nociceptive or mixed.
Products tested were pain creams compounded for neuropathic pain (ketamine, gabapentin, clonidine, and lidocaine), nociceptive pain (ketoprofen, baclofen, cyclobenzaprine, and lidocaine), or mixed pain (ketamine, gabapentin, diclofenac, baclofen, cyclobenzaprine, and lidocaine), compared to placebo.
Researchers reported that, for the primary outcome of average pain score one month after treatment, no differences were found in the mean reduction in average pain scores between the treatment and control groups for patients with 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]), or mixed pain (−0.3 points [CI, −0.9 to 0.2 points]), or for all patients (−0.3 points [CI, −0.6 to 0.1 points]).
After a month, 72 participants (36%) in the treatment groups and 54 (28%) in the control group had a positive outcome (risk difference, 8% [CI, −1% to 17%]),” according to the results.
— Steven P. Cohen, MD
Not Scientifically Meaningful
“With the number of research participants studied as long as they were studied, we should have been able to see a statistically significant difference in pain reduction if these creams were actually working,” Cohen pointed out. “But we didn’t see this in our data. The pain reduction we saw in patients being treated with the pain cream was nearly the same pain reduction we saw in placebo — there was just not a large enough difference for the reduction to be scientifically meaningful.”
Researchers conducted a double-blind, randomized and placebo-controlled study involving 399 participants, 18-90, at Walter Reed from August 2015 to February 2018. About 43% were active-duty military personnel, and the remaining participants were retired or dependents.
Participants were randomly divided into two groups — one for the compounded topical cream and the other a placebo cream. Then, the patients were divided into three equally numbered groups according to their history of chronic localized pain:
- neuropathic pain caused by disease or damage to the nerves, such as shingles or diabetes;
- nociceptive pain (non-neuropathic) caused by injury to tissue, such as burns or sprains; and
- so-called mixed pain caused by damage to the nerves and tissues, such as certain types of back pain.
Researchers noted that all of the participants had pain localized to specific areas: the face, back, buttocks, neck, abdomen, chest, groin and/or up to two extremities.
Results indicated that, for the neuropathic pain group, there was a 0.1-point difference between the drug group (-1.4) and the placebo group (-1.3). For the mixed pain group, meanwhile, there was a -1.3-point reduction for the placebo group, and a -1.6 reduction for the treatment group, for a difference of 0.3 points.
That all participants improved slightly throughout the study was probably do to the placebo effect, according to Cohen, who added that the effect tends to be stronger for pain treatment than for other medical disorder therapies.
“With the number of research participants studied as long as they were studied, we should have been able to see a statistically significant difference in pain reduction if these creams were actually working,” he added. “But we didn’t see this in our data. The pain reduction we saw in patients being treated with the pain cream was nearly the same pain reduction we saw in placebo — there was just not a large enough difference for the reduction to be scientifically meaningful.”
Researchers cautioned that the study had some limitations because of the wide variety of medical conditions and pain disorders among the participants and because capsaicin, a pepper derivative commonly used in lotions and creams for muscle pain, could not be used in the study compounds because the recognizable smell and application requirements would have undermined the double-blinding process that kept both caregivers and subjects unaware if they were getting active creams or placebos.
In conclusion, Cohen pointed out that, because of the high cost and relatively minor benefits from the creams, routine prescription and use of these compounded creams should not be encouraged.
Brutcher RE, Kurihara C, Bicket MC, Moussavian-Yousefi P, Reece DE, Solomon, LM, Griffith SR, Jamison DE, Cohen SP. Compounded Topical Pain Creams to Treat Localized Chronic Pain: A Randomized Controlled Trial. Ann Intern Med. 2019 Feb 5. doi: 10.7326/M18-2736. [Epub ahead of print] PubMed PMID: 30716769.
