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Topical Analgesics Help Curb Pain, Reduce Opioid Use

Topical Analgesics Help Curb Pain, Reduce Opioid Use

Interview with Edmund Harris, MD

Topical analgesics have been shown to reduce systemic exposure to opioids, limit side effects, and lower the risk of drug-drug interactions. According to a finding from the ongoing OPERA trial, they also could improve tolerability, reduce overall opioid use—all while managing primary pain symptoms.1

Topical analgesics can help curb pain, reduce opioid use.

“This is not an alternative way—this is an adjuvant way,” said Edmund Harris, MD, of Safe Harbor and Compliance Clinical Services, LLC. Much research already has documented the efficacy of topical agents for treating chronic pain, however, the lack of federal support for making these drugs more economically feasible likely has held back acceptance of this type of therapy, Dr. Harris said.2

Topical Opioids: Few Risks, Many Benefits

OPERA is an ongoing observational survey study looking at patients (ages 18-64) with chronic musculoskeletal and neuropathic pain who subsequently were prescribed topical analgesics. A total of 417 patients had been prescribed some form of topical drug, including:

  • Flurbiprofen (20%)
  • Amitriptyline (5%)
  • Magnesium Chloride (10%)
  • Gabapentin (6%)
  • Bupivicaine (2%)
  • Other transdermal gel

Patients completed 3 surveys during the study, all at different points in the treatment:

  • Survey 1: First patient visit before using the topical agent
  • Survey 2: Second patient visit approximately 45 days later
  • Survey 3: Third patient visit approximately 90 days later

By the third survey, patients appeared to have significantly less primary pain complaints and symptoms after incorporating topical analgesics for conditions like patient-reported arthritis, neuropathy, and myofascial/musculoskeletal pain or spasm (Tables 1 and 2). 

Overall Brief Pain Inventory (BPI) scores showed major improvements, where overall severity scores decreased by 31.3% (P< 0.001). Specifically, all 4 components of the BPI Severity score showed noticeable improvements (Figure 1), and the same held true for BPI Interference, which dropped markedly by 40.0% (Figure 2).

Topical drugs also appeared to be very well-tolerated by the patient population. Side-effects  were virtually non-existent, save for 3 patients (0.5%) reporting rash. Such findings were consistent with previous interim results incorporated in the trial, noted the researchers.

Topical agents, however, were not totally efficacious for every patient condition. Specifically, patients with tendinitis actually reported an increase (0.6%; P=1.0) in primary pain after 90 days. According to Dr. Harris, this result is not surprising given the affected site of pain is not known to be accessible through topical analgesia.

For other pain conditions though, the incorporation of topical agents appeared to be a valuable tool for improving patient outcomes.

Topical Agents Help Reduce Opioid Use

In light of the serious concerns about the long-term effects of chronic opioid therapy, topical agents could be a tool to lowering patients’ opioid intake.

“Right now is an optimal time for us to show that we can use our principles reasonably to allow us to reduce opioid usage, if it’s necessary,” said Dr. Harris. “We need to find the correct way—the rational approach, the physiological approach, a multipronged approach—so that we can reduce opioid use,” something that topical agents appear to do well.

In the study, patients reported a noticeable 27.5% reduction in use of oral opioids at 90 days (P < 0.001). Use of anti-inflammatory medications dropped dramatically by 64%, with a sizable 51.4% decrease in over-the-counter (OTC) medications (Figure 3).

Patients also reported satisfaction with the topical agents they used, finding they were convenient (86%), easy to apply (95%), and even preferred over their oral medications (76%).

Study Limitations

There are limitations to the study, including the interim analysis included all respondents, regardless of the fact more than one primary complaint was reported, which statistically changed from a mean of 2.2 to 1.8 by the third survey. According to Dr. Harris, future re-interrogations of the data likely will stratify the results into other helpful associations—for example, basing the data on agents the patients were taking and whether those agents contained ketoprofen. Incorporating a non-post-hoc control group to compare against is also another aim of Dr. Harris and his colleagues.

Some practitioners may have preconceived reservations about the usage of topical analgesics, such as concerns patients will apply too much or too little of the drug. However, given the accuracy of metered pumps for applying the drug, dosage accuracy should not be a major concern, noted Dr. Harris. Also, since the drug is concentrated at a specific site on the body, not administered systemically, the risk of toxicity is low compared to oral opioids.

Incorporating topical analgesics readily into the larger practice can be difficult. These drugs are typically more expensive than oral drugs and not incorporated by pharmacy benefit managers. These problems, which stem from the political and economic arenas, are “severe barriers” to the acceptance of adjuvant topical therapies, Dr. Harris noted.

“We have tried to get around this in several ways, having co-pay assistance and so forth…but in order for us to get the pharmacy benefit managers to pay for this, first we have to prove that it works. And that is what we have done, not just with this new study but beforehand, as well. The fact that opioid reduction and misuse diversion are there with these topical agents are just more reasons why to do it.”

This study was funded by Annie’s Apothecary in Kerrville, Texas; Annie’s Apothecary in Boerne, Texas; Boothwyn Pharmacy in Boothwyn, Pennsylvania; and Cypress Compounding Pharmacy in Houston, Texas. The authors of the study disclosed financial disclosures, including Drs. Gudin and Brennan, who are honoraria paid by Clarity Research and Consulting, LLC. Dr. Harris is a consultant for Clarity Research and Consulting, LLC. Dr. Dietze’s analysis of the study also was paid for by Clarity Research and Consulting, LLC. Click here to learn more about the OPERA trial.


1.     Gudin J, Brennan M, Harris E, et al. Decreased pain following use of a topical analgesic: Interim results from the Optimizing Patient Experience and Response to Topical Analgesics (OPERA) observational study. Poster presentation at: 8th Annual Meeting of the World Institute of Pain; May 20-23, 2016; New York, NY.

2.     Derry S, Wiffen P, Moore A. Topical nonsteroidal anti-inflammatory drugs for acute musculoskeletal pain. JAMA Clinical Evidence Synopsis. 2016;315(8):813-814.

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