Placebo and nocebo effects in headaches

As in the treatment of other pain conditions, the placebo and nocebo effects play an important role in the treatment of primary headache disorders, which are the most prevalent neurologic conditions worldwide with enormous personal and societal burden. Meta-analyses of randomized controlled trials (RCTs) for migraine prophylaxis revealed that 8 out of 20 participants treated with placebo experienced adverse events (AEs) and 1 out of 20 participants treated with placebo withdrew treatment because of AEs. Notably, the AEs in placebo groups mirrored the AEs expected of the medication in test, confirming that pretrial suggestions during the briefing of the participants by the researchers on the safety of the drug under test and the written consent to participate boost up the AEs in placebo-treated participants. In migraine RCTs, nocebo and placebo responses vary by the treatment duration, for example, nocebo response was higher in prophylactic than in symptomatic treatments, by treatment root of administration, for example, among prophylactic migraine treatments botulin toxin A showed the lowest nocebo response and the higher placebo response. Generally, the safer a treatment was (e.g., the less AEs recorded in the active treatment group) the less nocebo response was recorded (e.g., the less AEs recorded in the placebo treatment group). Nocebo and placebo responses were similar in trials for tension-type headache, but there is not enough evidence for cluster headache. To predict and prevent nocebo consequences a four-item self-fulfilled questionnaire (Q-No) has been developed, with 72% specificity and 67% sensitivity. This tool may help both investigators and practitioners to predict potential nocebo-behaviors and build personalized strategies to limit it, since nocebo effects are hampering treatment adherence and improve bad outcomes, in contrast to placebo effects. Large campaigns aiming to educate both physicians and citizens on the role of placebo and nocebo effects in medical therapeutics are required to improve headaches and public health, for example, vaccination and pharmaceutical prevention of several metabolic and vascular conditions.