Estimated Mean of Secondary Outcomes With Mixed Effects Longitudinal Regression Estimates in the TAU (n = 54) and C-OLP (n = 77) Groups
Morales-Quezada, overdose
Abbreviations: C-OLP, conditioned open-label placebo; NA, not applicable; PSQI, Pittsburgh Sleep Quality Index; TAU, treatment as usual; WHOQOL-BREF, World Health Organization Quality of Life assessment.Scores range from 0 to 100, with higher scores indicating higher quality of life.Scores range from 0 to 21, with higher scores indicating worse quality of sleep.Our unique implementation combined 2 methods to harness placebo effects: OLP and pharmacologic conditioning. In open-label studies, no pretense is made concerning the fact that the pill or device is physiologically inert. Patient participants are oriented transparently to the possible beneficial effects of placebos. We did not guide participant expectations regarding our specific study aims; rather, participants were informed of the nonspecific therapeutic benefits that can accompany placebo therapy but were not informed of the operationalization of assessments.Few studies have combined conditioning and OLP. In a novel small feasibility study, Morales-Quezada and colleaguesAlthough our results do not speak to mechanism, the beneficial effect of C-OLP on methadone treatment retention could be related to the benefits observed in sleep quality or other not-yet-assessed effects on overall function. As part of this RCT, we also obtained qualitative data from C-OLP participants to understand perceptions of efficacy—data that could help elucidate perceived benefits of C-OLP. A forthcoming study will represent these data in full.The clinical implications of the C-OLP intervention described in this study are great. Retention in treatment is a serious challenge for the field of addiction medicine and calls abound for an all hands on deck approach to identify solutions to stave overdose rates and increase treatment engagement and retention. We have demonstrated the general feasibility of administering a placebo adjunct to standard-of-care methadone in a community-based opioid treatment setting. Our experience running this trial showed us that C-OLP did not produce a significant burden to clinic procedures. Future studies should rigorously evaluate implementation outcomes, however (eg, patient and staff acceptability, measures of feasibility), to better inform the practicality of implementing a placebo adjunct to methadone treatment. Notwithstanding, the low-cost, low-risk nature of this intervention suggests that C-OLP could provide an appealing strategy to target early methadone treatment adherence. Well-powered studies are needed to evaluate this intervention’s efficacy on methadone treatment retention.