The information that clinicians provide to patients about a medication prescribed for their migraines can influence the magnitude of pain relief induced by the treatment, reports a study published online today in Science Translational Medicine. The findings suggest that patients who receive positive messages about the potential efficacy of their treatment may have better treatment outcomes than patients who receive negative messages.
The study involved 66 patients with recurring migraine attacks, which are characterized by symptoms such as debilitating headaches, nausea, sensitivity to light and even experiencing aura. Some research has linked the condition to ion channel defects in brain cells that cause certain neurons to become overactive.
Patients first recorded their baseline pain intensity on a scale from zero (no pain) to ten (maximal pain) for an untreated migraine attack. Then each study participant received a series of six envelopes containing treatment for six subsequent migraine attacks: two of the envelopes were labeled as “placebo”, two as “Maxalt” (the anti-migraine drug rizatriptan sold by the New Jersey-based pharmaceutical giant Merck) and two as “placebo or Maxalt.” However, for each pair of envelopes with identical labels, one envelope actually contained a placebo pill, whereas the other contained Maxalt.
Thirty minutes after the onset of headache, participants recorded their pain level and took their medication, and documented their pain level again two hours later. Notably, patients who had taken Maxalt mislabeled as “placebo” reported roughly 50% less pain relief than those who had taken the Maxalt labeled as “Maxalt.” This suggests that more than half of the drug effect was due to the placebo effect, says Ted Kaptchuk, a medical researcher who specializes in placebo effects at Harvard Medical School (HMS) in Boston and one of the authors of the study.
Co-author Rami Burstein, a headache expert at HMS, adds that labeling Maxalt as “placebo” likely reduced the effectiveness of Maxalt by giving patients negative expectations about the efficacy of the treatment. Similarly, he says, providing patients with a long list of possible side effects, risks, and adverse events in the context of prescribing a drug in clinical practice could give patients negative expectations, and therefore could potentially reduce drug efficacy, resulting in patients taking more drug.
A new twist
Strikingly, the study also revealed that placebo treatment mislabeled as Maxalt was just as effective in reducing pain as Maxalt mislabeled as placebo. “No one’s ever seen that before in human history, in my knowledge,” Kaptchuk says, referring to the comparison. “It raises the possibility that the placebo effect can be harnessed directly.”
Burstein speculates that the improvement in symptoms that occurred in patients who knowingly took the placebo pill may have occurred because people often become conditioned to associate taking a pill with feeling better, although he admits that his team cannot explain why or how the placebo treatment worked. However, he suggests that if a placebo treatment may help some patients, it should be considered as a treatment option for drugs whose benefits are associated with risky side effects.
“This study suggests that our expectancies and our mindset does have a role to play in how well our medicine works,” says Howard Brody, a medical ethicist at the University of Texas Medical Branch in Galveston who was not involved in the study. “It highlights that the information we provide for patients can be part of the healing experience, and can enhance the power of any other treatment we prescribe.” Brody says that he believes that clinicians can enhance patients’ expectations in practice in honest ways that do not deceive the patients, by being encouraging, compassionate and taking the time to listen to patients.