The role of cognitive and affective determinants in open-label placebo efficacy for migraine prevention

This dissertation examines the individual factors that moderate the effects of open-label placebos (OLPs) in migraine prophylaxis. Migraine is a common and highly disabling neurological disorder, and its pharmacological treatment is often limited by side effects. Placebo effects, mediated by expectations and conditioning, have substantial clinical relevance but usually require deception. In contrast, OLPs are administered transparently and thus offer an ethically acceptable way to harness placebo effects. In a randomized controlled trial, 120 patients with migraine received either OLPs in addition to treatment as usual (TAU) or TAU alone for 12 weeks. In addition to clinical endpoints (headache and migraine days, average pain intensity, pain-related disability, tolerability), potential moderators of OLP effects were assessed, including pain catastrophizing, fear of pain, stress, treatment expectations, as well as anxiety and depression. The aim was to examine whether and how these factors influenced treatment outcomes. While OLP treatment did not significantly reduce the number of headache or migraine days, it was associated with clinically relevant improvements in mental and physical health and increased perceived treatment efficacy. Moderation analyses indicated that stress, anxiety, and depression, in particular, influenced the effect of treatment on mental health and functional pain-related impairment. Notably, OLP treatment appeared to buffer the negative impact of these factors. Treatment expectations were also associated with positive changes in headache-related disability; however, the mediation analyses provided no evidence for a mediating role. In summary, this work provides key insights into the conditions under which OLPs exert their effects. The findings suggest that individual psychological characteristics—such as stress levels, emotional distress, and expectations—play a crucial role in shaping OLP efficacy. This dissertation thus offers a basis for more targeted, personalized applications of OLPs in clinical practice.