Supplemental Material for: Treatment Expectations across Open-Label Placebo and Pharmacological Contexts: A Randomized Clinical Trial in Chronic Low Back Pain

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.</p><p dir="ltr">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. </p><p dir="ltr">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.</p>