Because attitude is important in many aspects of our life, it’s natural to think that it may also shape our response to a particular medical treatment. Now, a new study on migraine headaches, published in Science Translational Medicine, suggests that a patient's expectations greatly influence the potential effects of both a medication and a placebo. "One of the many implications of our findings is that when doctors set patients' expectations high, [migraine drugs] become more effective," said Dr. Rami Burstein, the John Hedley-Whyte professor of anaesthesia at Harvard Medical School.

Migraine Triggers

Migraines, which afflict more women than men, are a type of throbbing headache often accompanied by nausea, sensitivity to light and sound, and even vomiting. Caused by abnormal brain activity, most sufferers soon learn they have particular "triggers" which may bring on an attack. Common triggers include: specific foods, alcohol, stress, and anxiety, particular odors, including smoking, some kinds of perfumes, loud noises, bright lights, missed meals, and changes in sleep patterns. Common foods identified by migraine sufferers consist of those that contain monosodium glutamate (MSG); those that are processed; chocolate, nuts, peanut butter, and dairy products; foods containing tyramine, such as aged cheese, smoked fish, chicken livers, figs, certain beans, and red wine; and meat containing nitrates, including bacon. In the United States, more than 37 million people suffer from migraines, and for many of those people, each migraine may last for at least four hours, and in some cases, for days. Worst of all, they are recurring.

Exploiting the recurring nature of migraine headaches, senior authors Burstein and Dr. Ted Kaptchuk, Harvard Medical School, led a research team in an examination of how much pain relief can be attributed to a drug's pharmacological effect and how much to placebo effect. As part of the study, they compared the effects of drug treatments and placebos on 66 individuals, each of whom suffered seven separate migraine attacks. Essentially, the investigators studied a total of over 450 attacks.

For each patient, the researchers requested they document an initial "no treatment" episode. Experiencing their first migraine in the study, patients described their headache pain and accompanying symptoms 30 minutes after the headache began, and then again two hours later. After this first episode, each participant was next given six envelopes, grouped in twos, and containing pills to be taken during each of their next six attacks. The pills, though, were weighted differently in terms of the patients’ expectations; the first pair of pills was spun positively and labeled "Maxalt" — rizatriptan, a type of migraine medication — the second pair was spun negatively and labeled "placebo," and the final pair of pills was given no spin at all and labeled "Maxalt or placebo."

Real Drug Or Placebo?

Simple as this sounds, the researchers had a trick up their sleeves: No matter what the label indicated, one of the two envelopes in each pair always contained a Maxalt tablet while the other always contained a placebo.

After being given their pills, the patients were asked to document their pain experiences in the same manner as they had done during the initial no-treatment session. What did the researchers discover? Consistently, each and every patient found the efficacy of the migraine medication boosted whenever their expectations were raised by a positive spin. Yet the same thing happened — they experienced more pain relief — when they were given positive information on an inert placebo. "When, for example, Maxalt was labeled 'Maxalt,' the subjects' reports of pain relief more than doubled compared to when Maxalt was labeled 'placebo,'” Kaptchuk stated in a press release. “This tells us that the effectiveness of a good pharmaceutical may be doubled by enhancing the placebo effect."

Oddly, the researchers also found that even when subjects were given a placebo labeled as "placebo," they reported pain relief, compared with no treatment. "Contrary to conventional wisdom that patients respond to a placebo because they think they're getting an active drug, our findings reinforce the idea that open label placebo treatment may have a therapeutic benefit," the authors said. Ultimately, then, not only did the benefits of Maxalt increase when patients thought they had received an effective drug, but patients reported similar pain reduction from placebo pills labeled "Maxalt" as from Maxalt tablets labeled "placebo."

"Our discovery showing that subjects' reports of pain were nearly identical when they were told that an active drug was a placebo as when they were told that a placebo was an active drug demonstrates that the placebo effect is an unacknowledged partner for powerful medications," Kaptchuk stated. In layman’s terms, this apparently is another case of “it’s all in your head.”

Source: Burstein R, Kaptchuk T, Kam-Hansen S, et al. Altered Placebo and Drug Labeling Changes the Outcome of Episodic Migraine Attacks. Science Translational Medicine. 2014.