Efficacy of a drug and placebo depending on the text on the label, a study in migraine attacks

BACKGROUND: The patient's expectations, partly based on the information provided by the physician, determine to a certain extent the effect of both drugs and placebos (Gebu 1997; 31: 1-6). American researchers wanted to quantify the effect of the text on the packaging label separately for a defined clinical picture.1 METHOD: In the chosen study design, a randomized investigator-blinded study, patients with migraine were alternately given drugs or placebos with different label texts. Participating patients were informed that the aim was to investigate the effect of rizatriptan (generic, Maxalt®) 10 mg and placebo on acute migraine. The researchers' hypothesis was that in an acute migraine attack the effect of both the active drug and the placebo would increase as the information provided on the label became more positive: negative (contains placebo), uncertain (50% chance), positive (contains active drug). All effects were compared with the pain intensity of the first attack during the study that had been untreated. The 66 participants had had migraine for at least six years, with and without aura, with an average of four attacks per month. Seven attacks were documented for each patient with a pain intensity of zero to ten (visual analogue scale (VAS)), to be reported half an hour after the onset (concurrent with the intervention) and two hours later, the primary outcome. After the first untreated attack, each patient received, in randomised order, either placebo or rizatriptan for the six subsequent attacks with one of three labels: contains placebo, uncertain content, or contains rizatriptan. A total of 453 attacks were fully documented. RESULTS: Baseline pain scores did not differ between the seven attacks. Without treatment, the pain score was always higher after two hours than after half an hour, whereas for the six treated attacks it was on average always lower. Both the label text (positive, uncertain, negative) and the treatment (rizatriptan, placebo) were related to the reduction in pain score. Rizatriptan provided twice as much pain relief as placebo. This was especially true for the packaging with a positive text and to the same extent for the packaging with an uncertain text. The (placebo) effect also increased with a placebo as the label text became more positive. A placebo with the text rizatriptan reduced the headache almost as well as a 'real' rizatriptan with the text placebo. A placebo labelled as a placebo was more effective than no treatment. Compared to no treatment, more than 50% of the effect of the medication was due to the placebo, regardless of the label text. RESEARCHERS' CONCLUSION: Increasingly positively presented information on the packaging label enhances the pain-relieving effect of both a placebo and active medication in migraine attacks. Even with correct text, the placebo effect remains. It is clear that whether a treatment involves active medication or a placebo, the information provided is an important element of pain relief.