Open-label dose-extending placebos for opioid use disorder: a protocol for a randomised controlled clinical trial with methadone treatment

Belcher, Annabelle M.; Cole, Thomas O.; Greenblatt, Aaron D.; Hoag, Stephen W.; Epstein, David H.; Wagner, Michael; Billing, Amy; Massey, Ebonie; Hamilton, Kristen R.; Kozak, Zofia K; Welsh, Christopher; Weintraub, Eric; Wickwire, Emerson M.; Wish, Eric D.; Kaptchuk, Ted J.; Colloca, Luana

doi:10.1136/bmjopen-2018-026604

Cited by 16 publications

(12 citation statements)

References 68 publications

(59 reference statements)

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“…Data were obtained as part of a randomized controlled trial employing a behavioral intervention ( ClinicalTrials.gov Identifier NCT02941809 ; Belcher et al, 2019 ). All data reported in this sub-study were obtained on the day of intake, prior to randomization and initiation of the clinical trial intervention.…”

Section: Methodsmentioning

confidence: 99%

“…All participants were recruited from a population of treatment-seeking patients presenting to the UMDTC clinic with a primary diagnosis of OUD. Recruitment methods are described in Belcher et al (2019) , but briefly: new patients requesting methadone treatment were approached on their first day of treatment in the clinic and asked if they were interested in hearing information about a compensated research study testing a novel behavioral approach to enhance methadone treatment outcomes. Following consent, participants were given several experimenter-administered assessments, one of which included a comprehensive drug use survey (described below).…”

Section: Methodsmentioning

confidence: 99%

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Race-based differences in drug use prior to onset of opioid use disorder

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Belcher

Massey

et al. 2021

Journal of Ethnicity in Substance Abuse

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Rates of opioid use disorder (OUD) have increased dramatically over the past two decades, a rise that has been accompanied by changing demographics of those affected. Early exposure to drugs is a known risk factor for later development of opioid use disorder; but how and whether this risk factor may differ between racial groups is unknown. Our study seeks to identify race differences in self-report of current and past substance use in OUD-diagnosed treatment-seeking individuals. Patients (n ¼ 157) presenting for methadone maintenance treatment at a racially diverse urban opioid treatment program were approached and consented for study involvement. Participants were administered substance use history questionnaires and urine drug screening at intake. Chi-square, t-tests, and rank-sum were used to assess race differences in demographic variables. Logistic and linear regressions assessed the relationship between race and substance use for binary and continuous variables, respectively. 61% of the population identified as Black and 39% as White. Black participants were significantly older; age was thus included as a covariate. Logistic regressions demonstrated that despite similar urine toxicology at intake, White participants were significantly more likely to report having used prescription opioids and psychedelic, stimulant, and sedative substance classes prior to their first use of non-pharmaceutical opioids. Compared to Black participants, White treatment-seeking OUD-diagnosed individuals reported using a wider range of substances ever and prior to first use of non-pharmaceutical opioids. There were no differences, however, in presentation for OUD treatment, suggesting different pathways to OUD, which may carry important clinical implications.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Race-based differences in drug use prior to onset of opioid use disorder

Deutsch‐Link

Belcher

Massey

et al. 2021

Journal of Ethnicity in Substance Abuse

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“…In particular, conditioning can be used to enhance an existing therapeutic response and, in some cases, to reduce one’s medication dosage in order to avoid side effects while maintaining the same level of efficacy (34, 39, 75). Dose reduction via placebo conditioning has been demonstrated to be effective with antihistamines for allergic reactions, methadone for those with opioid use disorder, melatonin for children with difficulties sleeping, antipsychotics for individuals diagnosed with schizophrenia, and corticosteroids for the treatment of psoriasis (76–80, 81). 7 This suggests that classically conditioned placebo responses can be used to support tapering or weaning off a medication entirely, opening up new avenues for patients for which treatments are effective but cannot be sustained.…”

Section: An Alternative View: Placebos As a Source Of Agencymentioning

confidence: 99%

Placebos as a Source of Agency: Evidence and Implications

Friesen

2019

Front. Psychiatry

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Bioethical discussions surrounding the use of placebos in clinical practice have long revolved around the moral permissibility of deceiving a patient if it is likely to benefit them. While these discussions have been insightful and productive, they reinforce the notion that placebo effects can only be induced through deception. This paper challenges this notion, looking beyond the paradigmatic clinical encounter involving deceptive placebos and towards many other routes that bring about placebo effects. After briefly describing the bioethical terrain surrounding the deceptive use of placebos in clinical practice, section 1 offers an examination of the various mechanisms known to contribute to placebo effects: classical conditioning, expectations, affective pathways, open-label placebo treatments, and additional factors that do not fall easily into a single category. The following section explores how each of these routes can be harnessed to bring about clinical benefits without the use of deception. This provides grounding for reconceiving of the placebo effect as a clinical tool that is not always in conflict with patient autonomy and can even be seen as a source of agency. In the final section, implications of the shift away from seeing placebos as necessarily deceptive are discussed. These include the necessity of looking beyond the clinical encounter and mainstream medicine as the primary sites of placebo responses, how important acknowledging the limits of placebo effects will be when we do so, as well as the difficulties of disentangling agency, responsibility, and blame within medicine.

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“…Clinical investigation of OLP effects has mainly focused on chronic pain (13)(14)(15)(16)(17), allergic (18,19), opioid use disorder (20), mental illness and psychosomatic symptoms (21)(22)(23)(24)(25)(26)(27)(28)(29). Evidence on OLP effects in acute pain on the other hand is limited, yet promising: Findings of two studies investigating the potential of Conditioned OLP (COLP) to reduce pain intensity and opioid dose in patients with spinal cord injury/polytrauma (30) and following spine surgery (31) suggest that COLP might also be effective in acute pain by showing reductions of opioid doses compared to Treatment As Usual (TAU).…”

Section: Introductionmentioning

confidence: 99%

Open-Label Placebo Treatment for Acute Postoperative Pain (OLP-POP Study): Study Protocol of a Randomized Controlled Trial

et al. 2021

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Introduction: Open-label placebos have been proposed as way of using long recognized analgesic placebo effects in an ethical manner. Recent evidence shows efficacy of open-label placebos for clinical conditions, but there is need for more research on open-label placebos in acute pain. In the treatment of acute postoperative pain, minimization of opioid related side effects remains one of the key challenges. Therefore, this study aims at investigating the potential of adding unconditioned open-label placebos to treatment as usual as a means of reducing opioid consumption and its related side effects in patients with acute postoperative pain.Methods and Analysis: This is the protocol of an ongoing single site randomized controlled trial. The first patient was enrolled in May 2020. In total, 70 patients suffering from acute postoperative pain following dorsal lumbar interbody fusion are randomized to either a treatment as usual group or an experimental intervention group. The treatment as usual group consists of participants receiving a patient-controlled morphine pump. On day 1 and 2 post-surgery, patients in the intervention group receive, in addition to treatment as usual, two open-label placebo injections per day along with an evidence-based treatment rationale explaining the mechanisms of placebos. The primary outcome is measured by means of self-administered morphine during day 1 and 2 post-surgery. Several other outcome measures including pain intensity and adverse events as well as potential predictors of placebo response are assessed. Analysis of covariance will be used to answer the primary research question and additional statistical techniques such as generalized linear mixed models will be applied to model the temporal course of morphine consumption.Discussion: This study will provide valuable insights into the efficacy of open-label placebos in acute pain and will potentially constitute an important step toward the implementation of open-label placebos in the clinical management of acute postoperative pain. In addition, it will shed light on a cost-efficient and patient-centered strategy to reduce opioid consumption and its related side effects, without any loss in pain management efficacy.Ethics and Dissemination: The “Ethikkommission Nordwest- und Zentralschweiz” (BASEC2020-00099) approved the study protocol. Results of the analysis will be submitted for publication in a peer-reviewed journal.Clinical Trial Registration: The study is registered at ClinicalTrials.gov (NCT04339023) and is listed in the Swiss national registry at kofam.ch (SNCTP000003720).

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Open-label dose-extending placebos for opioid use disorder: a protocol for a randomised controlled clinical trial with methadone treatment

Cited by 16 publications

References 68 publications

Race-based differences in drug use prior to onset of opioid use disorder

Race-based differences in drug use prior to onset of opioid use disorder

Placebos as a Source of Agency: Evidence and Implications

Open-Label Placebo Treatment for Acute Postoperative Pain (OLP-POP Study): Study Protocol of a Randomized Controlled Trial

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