The prediction of the analgesic placebo response is moderated by outward-focused attention: A sham, randomized clinical trial of chronic back pain patients

The within-subject variability (WSV) of pain-intensity reports has gained attention as a predictor of the placebo response but has demonstrated mixed results. We hypothesized that participants’ inward- and outward-directed attention will moderate WSV's prediction of the analgesic placebo response. In this sham randomized clinical trial (protocol number NCT05994118); placebo response was induced in chronic back-pain patients (n=113) through a saline injection plus verbal suggestion. The WSV assessed by the focused analgesia selection test (FAST) served as a predictor. The revised Self-Consciousness Scale (SCS-R), evaluating a person's tendency to focus attention inward or outward was used to moderate the prediction. The placebo response prediction was significantly moderated by 2 SCS-R subscales: public self-consciousness (b = 46.36, SE = 23.08, t = 2.0, p = 0.047) and social anxiety (b = 44.01, SE = 18.02, t = 2.44, p = 0.016). The prediction was significant at low levels of both moderators (p < 0.01), but not at high levels of these traits. Prediction of the placebo response is of value and could promote personalized medical care. Better understanding of factors shaping the placebo response could further contribute to both clinical practice and clinical trials. Perspective: The current study demonstrates that the prediction of the analgesic placebo response could be improved if relevant personal characteristics are included as moderators of the prediction. Better predictions of the placebo response could contribute to improve both clinical research and clinical care.