Does Conditioning With Open-Label Placebo Reduce Postsurgical Pain?

doctor explaining medication to patient
Researchers investigated whether conditioning with an open-label placebo right after spinal surgery could reduce patients’ opioid use and postsurgical pain.

After spinal surgery, conditioning with an open-label placebo (COLP) decreased opioid consumption. These findings from a randomized, controlled trial were published in Pain.

Patients (N=41) were recruited before surgery at Brigham and Women’s Hospital between 2018 and 2020. Patients were instructed about the placebo effect prior to inclusion in the study and were randomized to self-administer COLP after surgery with oxycodone (5-10 mg) or hydromorphone (1-2 mg) available every 4 to 6 hours (n=19) or to receive usual care (n=22). Patients were assessed for sensitization, pain tolerance and threshold, and consumption of opioids.

Patients in the COLP and usual care group were aged 59.1 (±13.1) and 61.2 (±13.0) years, and 37% and 59% were women, respectively. The Baseline Brief Pain Inventory score was average 5.3 (±2.6) and 5.4 (±1.4), and 11% and 18% were using opioids.

Surgery was performed on the cervical, thoracic, sacral, and/or lumbar spine, and 46% of surgeries required remifentanil and sufentanil infusions. Opioid consumption during surgery and in the inpatient unit were similar between groups.

For the 17 days following surgery, patients in the COLP group consumed 30% fewer opioids (b, -15.90; c2, 5.93; P =.015). At day 7, 68% of the COLP recipients remained on opioids compared with 94% of the usual care group, and by day 14, the percentage of those on opioids declined to 52.6% and 75%, respectively.

Patients in the COLP group reported lower values of maximum pain (b, -1.03; c2, 4.50; P =.034) but similar average pain (b, -0.70; c2, -1.59; P =.122).

Among the COLP group, stratified by baseline pain scores (out of 10), patients with greater pain were more likely to have lower maximum pain (7.25: -1.94; 95% CI, -2.46 to -1.43 vs 3: -0.20; 95% CI, -0.78 to 0.38). Women were more likely to have an effect from the placebo (-26.0; 95% CI, -33.22 to -18.73 morphine mg equivalents [MME]) compared with men (-4.89; 95% CI, -11.47 to 1.70 MME) as were younger patients (48 years: -28.64; 95% CI, -35.24 to -22.04 vs 72 years: -4.12; 95% CI, -10.67 to 2.43 MME).

This study was limited by its low sample size and by including only 1 type of surgery. Further exploration is needed to determine whether the open-label placebo may be useful for other surgery types.

These findings suggest that a subset of patients may be able to reduce their opioid consumption following spinal surgery with education about the placebo effect and self-administering placebo pills.


Flowers KM, Patton ME, Hruschak VJ, et al. Conditioned open-label placebo for opioid reduction following spine surgery: a randomized, controlled trial. Published online January 11, 2021. Pain. doi:10.1097/j.pain.0000000000002185