Placebo Effect of Verbal Instructions Coupled with Pharmacological Treatment: Results from a Randomized Controlled Trial in Migraine Patients

Abstract – Introduction: Verbal instructions modulate the expectation concerning a given drug. Knowing that the prescribing clinician is positive and enthusiastic toward the prescribed treatment may lead to positive expectations. We tested whether administering strongly positive verbal instructions together with a pharmacological prescription might trigger a placebo effect in migraine patients. Methods: Outpatients (n = 102) were randomly assigned to: (a) an experimental condition: the pharmacological prescription was coupled to strongly positive verbal instructions; (b) a control condition: the prescription was coupled to positive verbal instructions. Subjects were assessed before the prescription (T0), 7 days (T1), 15 days (T2), 1 month (T3), 2 months (T4), and 3 months after it (T5). At each assessment point, Headache Impact Test (HIT-6) and two Numeric Rating Scales (NRSs) were proposed. Kellner’s scale of change was administered at T1–T5. Results: Patients who received strongly positive instructions had no HIT decrease (p = 0.177; η2 = 0.034). Patients who received positive instructions had HIT decrease (p = 0.006; η2 = 0.770). No difference was found between the groups. No significant across timepoints change of expectations was observed in the group who received strongly positive instructions (p = 0.433; η2 = 0.021) or in the group who received positive instructions (p = 0.151; η2 = 0.037). Since the first group had a decrease across timepoints of the score while the second group had a peak at T2, difference between them was statistically significant (p = 0.029; η2 = 0.049). Conclusion: Strongly positive verbal instructions did not produce placebo effect.