Effectiveness of Conditioned Open-label Placebo With Methadone in Treatment of Opioid Use Disorder: A Randomized Clinical Trial.

Importance: Methadone 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. Objective: To 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 Participants: This 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. Interventions: Participants 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 Measures: Outcomes 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. Results: Of 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 Relevance: In 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 Registration: ClinicalTrials.gov Identifier: NCT02941809.

Adversity, Maltreatment, and Resilience in Young Children.

BACKGROUND: Much of the research on children in high risk environments, particularly those who have been maltreated, has focused on negative outcomes. Yet, much can be learned from some of these children who fare relatively well. The objective was to examine resilience in high-risk preschoolers, and to probe contributors to their adaptive functioning. METHODS: The sample of 943 families was from the Longitudinal Studies of Child Abuse and Neglect, a consortium of 5 sites, prospectively examining the antecedents and outcomes of maltreatment. Most of the families were at high risk for maltreatment, and many had been reported to Child Protective Services (CPS) by the time the children were aged 4 years. Standardized measures were used at ages 4 and 6 to assess the children's functioning in behavioral, social and developmental domains, and parental depressive symptoms and demographic characteristics. Maltreatment was determined on the basis of CPS reports. Logistic regressions were conducted to predict resilience, defined as competencies in all 3 domains, over time. RESULTS: Forty-eight percent of the sample appeared resilient. This was associated with no history of maltreatment (odds ratio = 1.50; 95% confidence interval [CI], 1.02-2.20; P = .04), a primary caregiver reporting few depressive symptoms (odds ratio = 2.19; 95% CI, 1.63-2.94; P < .001), (P = .014), and fewer children in the home (P = .03). CONCLUSIONS: Almost half of the sample appeared resilient during this important developmental period of transition to school. This enables clinicians to be cautiously optimistic in their work with high-risk children and their families. However, more than half the sample was not faring well. Child maltreatment and caregiver depressive symptoms were strongly associated with poor outcomes. These children and families deserve careful attention by pediatric practitioners and referral for prevention and early intervention services.

High rates of behavioral problems in perinatally HIV-infected children are not linked to HIV disease.

OBJECTIVE: Descriptive studies and clinical reports have suggested that human immunodeficiency virus (HIV)-positive children are at risk for behavioral problems. Inadequate control groups and sample sizes have limited the ability of investigators to consider multiple influences that place HIV-positive children at risk for poor behavioral outcomes. We examined the unique and combined influences of HIV, prenatal drug exposure, and environmental factors on behavior in children who were perinatally exposed to HIV. METHODS: Participants included 307 children who were born to HIV-positive mothers (96 HIV infected and 211 seroreverters) and enrolled in a natural history, longitudinal study of women to infant HIV transmission. Caregivers completed parent behavioral rating scales, beginning when the children were 3 years old. Data were also collected on prenatal drug exposure; child age, gender, and ethnicity; caregiver relationship to child; and birth complications. RESULTS: Multivariate analyses comparing the HIV-infected children with perinatally exposed but uninfected children from similar backgrounds failed to find an association between either HIV status or prenatal drug exposure and poor behavioral outcomes. The strongest correlates of increased behavioral symptoms were demographic characteristics. CONCLUSIONS: This study suggests that although a high prevalence of behavioral problems does exist among HIV-infected children, neither HIV infection nor prenatal drug exposure is the underlying cause. Rather, other biological and environmental factors are likely contributors toward poor behavioral outcomes.