Prevalence of the placebo and nocebo responses in patients with migraine and tension- type headache

Introduction Placebo and nocebo responses have not been adequately investigated in patients with primary headaches. In randomized clinical trials of analgesic, approximately 30% of the patients with migraine showed a placebo effect. However, a tremendous variation among the different studies was observed. The purpose of this study was to evaluate the prevalence of placebo and nocebo responses in a large group of patients with migraine or tension-type headache recruited from a university-based Headache Centre. Methods A total of 726 consecutive patients (208 men, 518 women; mean age±SD=41.9±16.0 years), attending the Headache Centre of the University of Turin (Italy), were involved in the study. The diagnosis of migraine was made according to ICHD-II criteria. The patients underwent an extensive physical and neurological examination. Psychological evaluation was performed using the BDI, the STAI X-1 and STAI X-2 tests. A standardized record of all the clinical and psychological characteristics of headache was obtained. Patients were divided into three groups: A) migraine (with and without aura): 258 patients; B) tension-type headache (episodic and chronic): 137 patients, and C) mixed headaches (migraine and tension-type headache): 331 patients. Patients received a tablet containing talcum powder and were told, according to the presence or absence of pain, that the pill was able to produce a pain decrease or increase (extinction or induction of pain). Three hundred and twenty-five patients performed the placebo test and 401 the nocebo test. Patients recorded on the headache diary the presence or absence of headache in the 4 hours following the test. Results A placebo response was observed in 31.1% of migraine patients, in 38.7% of patients with tension-type headache and in 270 34.0% of patients with mixed headache. A nocebo effect was reported by 12.% of migraine patients, 22.7% of patients with tension-type headache and 19.7% of patients with mixed headache. Placebo and nocebo effects were not influenced by age, gender or headache diagnosis. Nocebo responders had a longer duration of the disease than non-responders. Discussion Our study showed that approximately one-third of patients with migraine or tension-type headache presented a placebo response. The nocebo effect was reported by 15% of the patients. The placebo and nocebo responses were not influenced by age, gender or disease diagnosis. Duration of the disease may influence the nocebo response.