Ineffective Drug Versus Poor Adherence

In the world of dermatology, topical corticosteroids are the most widely used treatments. They are used to treat a broad array of inflammatory skin disease. A central dogma of dermatology—a dogma I learned in my own training and for many years taught to my trainees—is that while topical steroids may be very effective initially, they gradually lose effectiveness. The phenomenon has been termed “tachyphylaxis.” Tachyphylaxis has been defined as “the more you use the topical steroid, the less it works.” The underlying pathophysiologic basis for the loss of activity has been elusive. The phenomenon did not seem to be due to down-regulation of steroid hormone receptors, as switching from one brand of topical steroid that isn’t working to another brand of topical steroid of the same strength often resulted in treatment success.

A window on understanding the tachyphylaxis problem was opened when research used electronic adherence monitors on containers of the topical steroids. Use of the medication steadily declined over time. The well-established “more you use it, less it works” dogma was turned on its head (it’s “the less you use it, the less it works”). Once we understood that tachyphylaxis was due to poor adherence to treatment, the previously enigmatic ability of a different brand to be effective was no longer so puzzling or difficult to explain.

Basic pharmacology textbooks are strong on GI absorption, first-past effects on the liver, urinary excretion and drug interactions, but the critical aspect of poor adherence is too often neglected. The clinical trials that are the foundation of new drug development quantitatively assess the effects of drugs using in vitro systems, animal models and human studies. Every aspect of absorption, distribution and excretion is examined. Drug interactions are assessed, as are effects on cardiac function. But rarely does anyone ask, “Are the research subjects actually taking the medication?” The mountain of evidence that gets trucked to the FDA for evaluation probably contains no objective information (aside from unreliable self-reported diaries or pill counts) to assess adherence to treatment.

Adherence plays a critical role in effectiveness of treatment, the frequency (or paucity) of adverse events, variation in response among different people and different settings, refill rates, sales and revenues. Sure, let’s fund basic research to understand the factors that cause human disease, and let’s continue to develop new, better medications to ease human suffering. Doing pharmacogenomics studies may be valuable, too. But let’s not forget to invest in developing and implementing new ways to encourage patients to take their medication regularly, as those measures are likely to be more effective, less costly, easier and faster to deploy than finding and getting approval for the next blockbuster drug.

Adherence should be top of mind in pharmaceutical development, marketing and practice. When you seek to explain some unusual or puzzling question about medications, don’t assume that patients are taking the medication. Consider the possibility that poor adherence may be playing a role in how the medicine is working or how it is selling. As you look at how to market your medications, make sure your plans address adherence to treatment. By encouraging patients to be adherent to treatment, medication use will be improved and patients’ outcomes with be enhanced, while improving sales of product.

  • Steven Feldman, M.D.

    Dr. Steven Feldman is Professor of Dermatology and Public Health Sciences at Wake Forest Baptist Medical Center. Steve studies patient adherence at North Carolina’s Wake Forest Baptist Medical Center. He is also Chief Science Officer of Causa Reseach, an adherence solutions company (, founder of, and author of “Compartments” and “An Illustrated Dictionary of Behavioral Economics for Healthcare Professionals.”


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