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Conditioned open-label placebo for opioid reduction after spine surgery: a randomized controlled trial.

ABSTRACT:

Abstract

Placebo effects have traditionally involved concealment or deception. However, recent evidence suggests that placebo effects can also be elicited when prescribed transparently as "open-label placebos" (OLPs), and that the pairing of an unconditioned stimulus (eg, opioid analgesic) with a conditioned stimulus (eg, placebo pill) can lead to the conditioned stimulus alone reducing pain. In this randomized control trial, we investigated whether combining conditioning with an OLP (COLP) in the immediate postoperative period could reduce daily opioid use and postsurgical pain among patients recovering from spine surgery. Patients were randomized to COLP or treatment as usual, with both groups receiving unrestricted access to a typical opioid-based postoperative analgesic regimen. The generalized estimating equations method was used to assess the treatment effect of COLP on daily opioid consumption and pain during postoperative period from postoperative day (POD) 1 to POD 17. Patients in the COLP group consumed approximately 30% less daily morphine milligram equivalents compared with patients in the treatment as usual group during POD 1 to 17 (-14.5 daily morphine milligram equivalents; 95% CI: [-26.8, -2.2]). Daily worst pain scores were also lower in the COLP group (-1.0 point on the 10-point scale; 95% CI: [-2.0, -0.1]), although a significant difference was not detected in average daily pain between the groups (-0.8 point; 95% CI: [-1.7, 0.2]). These findings suggest that COLP may serve as a potential adjuvant analgesic therapy to decrease opioid consumption in the early postoperative period, without increasing pain.

SUBMITTER: Flowers KM

PROVIDER: S-EPMC8378225 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceMethadone treatment is the most effective evidence-based treatment for opioid use disorder (OUD), but challenges related to dosing and premature treatment dropout argue for adjunct interventions to improve outcomes. One potential behavioral intervention with low risk involves harnessing placebo effects.ObjectiveTo determine the effect of a pharmacologically conditioned open-label placebo (C-OLP) on 90-day methadone dose, retention, drug use, withdrawal, craving, quality of life, and sleep.Design, setting, and participantsThis 2-arm, open-label, single-blind randomized clinical trial was conducted between December 5, 2017, and August 2, 2019, in an academically affiliated community opioid treatment program. Analyses were conducted between October 1, 2019, and April 30, 2020. A total of 320 newly enrolled adults seeking treatment for moderate to severe OUD were assessed for study eligibility; 131 met eligibility criteria, provided informed consent, and were randomized to either C-OLP or treatment as usual (TAU) in an unequal-block (3:2) manner. Exclusion criteria were pregnancy, hospital/program transfers, and court-ordered treatment.InterventionsParticipants randomized to C-OLP received pharmacologic conditioning and a placebo pill and methadone, and participants randomized to TAU were given methadone only. Participants met with the study team 5 times: at baseline (treatment intake) and 2, 4, 8, and 12 weeks postbaseline. Interactions were balanced between the 2 groups.Main outcomes and measuresOutcomes included 90-day methadone dose (primary) and treatment retention, drug use, withdrawal, craving, quality of life, and sleep quality (secondary). Analyses were conducted as intention-to-treat.ResultsOf the 131 people enrolled in the study, 54 were randomized to TAU and 77 to C-OLP. Mean (SD) age was 45.9 (11.2) years; most of the participants were Black or African American (83 [63.4%]) and male (84 [64.1%]). No significant group differences were observed in the mean (SD) 90-day methadone dose (83.1 [25.1] mg for group TAU, 79.4 [19.6] mg for group C-OLP; t = 0.621991; P = .43), but the groups differed significantly in their retention rates: 33 (61.1%) for TAU and 60 (77.9%) for C-OLP (χ21 = 4.356; P = .04; number needed to treat for the beneficial outcome of 3-month treatment retention, 6; 95% CI, 4-119). C-OLP participants also reported significantly better sleep quality.Conclusions and relevanceIn this randomized clinical trial, C-OLP had no effect on the primary outcome of 90-day methadone dose. However, C-OLP participants were significantly more likely to remain in treatment. These findings support the use of C-OLP as a methadone treatment adjunct, but larger trials are needed to further examine the use of C-OLP.Trial registrationClinicalTrials.gov Identifier: NCT02941809.

Project description:IntroductionPatients with head and neck cancer have a substantial risk of chronic opioid dependence following surgery due to pain and psychosocial consequences from both the disease process and its treatments. Conditioned open-label placebos (COLPs) have been effective for reducing the dose of active medication required for a clinical response across a wide range of medical conditions. We hypothesise that the addition of COLPs to standard multimodal analgesia will be associated with reduced baseline opioid consumption by 5 days after surgery in comparison to standard multimodal analgesia alone in patients with head and neck cancer.Methods and analysisThis randomised controlled trial will evaluate the use of COLP for adjunctive pain management in patients with head and neck cancer. Participants will be randomised with 1:1 allocation to either the treatment as usual or COLP group. All participants will receive standard multimodal analgesia, including opioids. The COLP group will additionally receive conditioning (ie, exposure to a clove oil scent) paired with active and placebo opioids for 5 days. Participants will complete surveys on pain, opioid consumption and depression symptoms through 6 months after surgery. Average change in baseline opioid consumption by postoperative day 5 and average pain levels and opioid consumption through 6 months will be compared between groups.Ethics and disseminationThere remains a demand for more effective and safer strategies for postoperative pain management in patients with head and neck cancer as chronic opioid dependence has been associated with decreased survival in this patient population. Results from this study may lay the groundwork for further investigation of COLPs as a strategy for adjunctive pain management in patients with head and neck cancer. This clinical trial has been approved by the Johns Hopkins University Institutional Review Board (IRB00276225) and is registered on the National Institutes of Health Clinical Trials Database.Trial registration numberNCT04973748.

Project description:ObjectiveAbnormal glutamatergic neurotransmission is implicated in the pathophysiology of autism spectrum disorder (ASD). In this study, the safety, tolerability, and efficacy of the glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist memantine (once-daily extended-release [ER]) were investigated in children with autism in a randomized, placebo-controlled, 12 week trial and a 48 week open-label extension.MethodsA total of 121 children 6-12 years of age with Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR)-defined autistic disorder were randomized (1:1) to placebo or memantine ER for 12 weeks; 104 children entered the subsequent extension trial. Maximum memantine doses were determined by body weight and ranged from 3 to 15?mg/day.ResultsThere was one serious adverse event (SAE) (affective disorder, with memantine) in the 12 week study and one SAE (lobar pneumonia) in the 48 week extension; both were deemed unrelated to treatment. Other AEs were considered mild or moderate and most were deemed not related to treatment. No clinically significant changes occurred in clinical laboratory values, vital signs, or electrocardiogram (ECG). There was no significant between-group difference on the primary efficacy outcome of caregiver/parent ratings on the Social Responsiveness Scale (SRS), although an improvement over baseline at Week 12 was observed in both groups. A trend for improvement at the end of the 48 week extension was observed. No improvements in the active group were observed on any of the secondary end-points, with one communication measure showing significant worsening with memantine compared with placebo (p?=?0.02) after 12 weeks.ConclusionsThis trial did not demonstrate clinical efficacy of memantine ER in autism; however, the tolerability and safety data were reassuring. Our results could inform future trial design in this population and may facilitate the investigation of memantine ER for other clinical applications.

Project description:BackgroundRecent studies indicate that the administration of open-label placebos (OLP) can improve symptoms in various medical conditions. The primary aim of this 3-week randomized controlled trial was to examine the effects of OLP treatments on pain, functional disability, and mobility in patients with arthritic knee pain.MethodsSixty patients (55% females; mean age, 66.9 ± 9.7 SD years) were randomized to one of two OLP treatments (n = 41) or no treatment (NT; n = 19). OLP treatments were accompanied by the verbal suggestion "to decrease pain" (OLP-pain, n = 20) or "to improve mood" (OLP-mood, n = 21). Pain and mood levels were monitored on 11-point Numeric Rating Scales (NRSs) in a patient diary, and global clinical improvement (CGI-I) was assessed at the end of the study. At baseline and after 21 days, patients filled in validated questionnaires to assess symptoms and functional disability of the knee (WOMAC), mental and physical quality of life (SF-36), state anxiety (STAI-state), perceived stress (PSQ-20), and self-efficacy (GSE). In addition, knee mobility (neutral zero-method), heart rate variability (HRV), and diurnal cortisol levels were evaluated before and after treatment.ResultsEvaluation of daily pain ratings indicated significant pain decrease in the OLP groups compared to NT (p = 0.013, d = 0.64), with no difference between the OLP-pain and the OLP-mood groups (p = 0.856, d = 0.05). OLP treatment also improved WOMAC pain (p = 0.036, d = 0.55), again with no difference between the two OLP groups (p = 0.65, d = 0.17). WOMAC function and stiffness, knee mobility, stress, state anxiety, quality of life, and self-efficacy did not change differently between groups.ConclusionOLP treatment improved knee pain in elderly patients with symptomatic knee osteoarthritis (OA), while functional disability and mobility of the knee did not change. The content of the verbal suggestion was of minor importance. OLP administration may be considered as supportive analgesic treatment in elderly patients with symptomatic knee OA.Trial registrationGerman Clinical Trials Register (https://www.drks.de/), DRKS00015191 (retrospectively registered).

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Conditioned open-label placebo for opioid reduction after spine surgery: a randomized controlled trial.

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