Treatment Expectation across Open-Label Placebo and Pharmacological Contexts: A Randomized Clinical Trial in Chronic Low Back Pain

Abstract

Introduction Chronic low back pain (CLBP) markedly reduces quality of life and remains difficult to treat. Increasing opioid prescriptions highlight the need for effective innovative approaches. This randomized controlled trial aims to investigate whether social observational learning augments analgesic or open-label placebo treatment through treatment expectation modulation in CLBP patients. Methods One hundred thirty patients with CLBP were randomized into a 2 × 2 fully balanced placebo design plus a natural history (NH) control group. Patients received a 3-week treatment with novamine sulfone (analgesic) or open-label placebos (OLP), with follow-up at 3 months. Expectations were manipulated before treatment, using a positive social observational learning video (SoL) or a neutral control video (neutral). Pain intensity (numeric rating scale, NRS 0–10) was the primary outcome. Secondary outcomes included treatment expectations and functional capacity. Results Pain intensity decreased significantly over time in all treatment groups (p < .001), with the smallest reduction in NH. Pain reduction in OLP + SoL and in analgesic + neutral was significantly greater than NH (p < .05). Expectation manipulation produced significant group differences in expected pain relief (p < .05). Higher expected pain relief predicted greater pain reduction after 3 weeks and 3 months (both p < .001). Functional capacity improved over time (p < .001) without consistent group differences. Conclusion Open-label placebos combined with social observational learning produced clinically meaningful analgesia that did not significantly differ from active medication. Treatment expectation represents a key mechanism underlying pain relief in CLBP and calls for further investigation.