Compounded topical pain creams to treat localized chronic pain: A randomized controlled trial

Background: The use of compounded topical pain creams has increased dramatically, yet their effectiveness has not been well evaluated. Objective: To determine the efficacy of compounded creams for chronic pain. Design: Randomized controlled trials of 3 interventions. (ClinicalTrials.gov: NCT02497066) Setting: Military treatment facility. Participants: 399 patients with localized pain classified by each patient's treating physician as neuropathic (n = 133), nociceptive (n = 133), or mixed (n = 133). Intervention: 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), or placebo. Measurements: The primary outcome measure was 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 through 3 months. Results: For the primary outcome, 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]). At 1 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%]). Limitations: Generalizability is limited by heterogeneity among pain conditions and formulations of the study interventions. Randomized follow-up was only 1 month. Conclusion: Compounded pain creams were not better than placebo creams, and their higher costs compared with approved compounds should curtail routine use. Primary Funding Source: Centers for Rehabilitation Sciences Research, Defense Health Agency, U.S. Department of Defense.