Open-Label Placebo Improves Patient Retention in Methadone Treatment for Opioid Use Disorder

A pharmacologically conditioned open-label placebo (C-OLP) may be an effective methadone adjunct, as recipients with opioid use disorder (OUD) were more likely to remain in treatment, according to study findings published in JAMA Network Open.

Some emerging evidence suggests that harvesting the placebo effect in the treatment of OUD may result in favorable outcomes.

The single-center, randomized clinical trial (ClinicalTrials.gov Identifier: NCT02941809) enrolled patients (N=131) with OUD seeking medications for OUD. Study participants received education about the placebo effect and were randomly assigned to receive C-OLP (n=77) or treatment as usual (n=54) during a 12-week methadone intervention. The C-OLP recipients were instructed to take 1 placebo pill daily during the first 2 weeks followed by 2 pills daily up to week 12. The primary outcome was methadone dose at 3 months.

The study participants had a mean [SD] age of 45.9[11.2] years, 64.1% were men, 63.4% were Black, and they had been using opioids for 22.9[12.8] years. At the baseline urine screening, 93.1% were positive for opioids, 72.5% for cocaine, 33.6% for benzodiazepines, 22.9% for tetrahydrocannabinol, and 4.6% were methamphetamine.

No group differences in methadone dose were observed throughout the study and ranged between 10 and 40 mg. At 90 days, the mean dose was 83.1[25.1] mg for the control individuals and 79.4[19.6] mg for the C-OLP recipients (P =.43).

The treatment retention rate was higher for the C-OLP recipients (77.9%) compared with control individuals (61.1%; P =.04).

There were no significant group differences for secondary outcomes of self-reported drug use in the previous 2 weeks, withdrawal symptoms, cravings, or quality of life. However, the C-OLP recipients reported improved Pittsburgh Sleep Quality Index (PSQI) scores vs control individuals (mean, 8.12 vs 9.9; P =.047), respectively.

The limitations of this study include the low power; the study was not adequately powered to detect significant differences in the secondary outcomes.

These data indicated that a C-OLP may improve retention in methadone treatment for OUD. The study authors concluded, “Our findings of C-OLP-enhanced treatment retention and ameliorated sleep merit further investigation, especially considering the unchecked OUD epidemic that continues in the US.”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the author’s disclosures.