Effects of open-label placebos across outcomes and populations: An updated systematic review and meta-analysis of randomized controlled trials

This work synthesizes and updates findings from four previous systematic-reviews and meta-analyses on open-label placebos (OLPs). For the first time, it directly tests whether OLPs have different effects on self-report versus objective outcomes and on clinical versus non-clinical samples. We searched eight data-bases up to November 9, 2023, and included 58 randomized controlled trials (RCTs), compromising 61 separate comparisons. OLPs yielded a small positive effect across various health-related conditions (k = 61, n = 4569, SMD = 0.36, 95% CI = 0.26; 0.45, p < 0.0001; I² = 56%). The OLP effect differed between self-report outcomes (k = 55, n = 3171, SMD = 0.40) and objective outcomes (k = 14, n = 1176, SMD = 0.02, Q = 9.81, p < 0.01), and between clinical samples (k = 22, n = 1398, SMD = 0.48) and non-clinical samples (k = 39, n = 3,171, SMD = 0.29, Q = 4.69, p < 0.05). Neithter the level of suggestiveness nor the type of control moderated the effect. These findings confirm on a large dataset that OLPs are effective for self-report but not for objective outcomes. They also point to potential differences in effectiveness and mechanisms in comparsion to deceptive placebos.