Faculty Bibliography

BACKGROUND:Despite the existence of effective pharmacotherapies, rates of opioid use disorder and opioid overdose deaths have continued to increase. Emergency department (ED) visits provide an important opportunity to engage in treatment patients with untreated opioid use disorder (OUD). Case management implemented in other settings is effective in linking those with opioid and other drug use disorders to longer-term treatment, but research has not established its efficacy in the ED. Here we report the results of a trial of Strengths-Based Case Management (SBCM) for people with untreated OUD who are identified during ED visits, with the primary goal of linking them to pharmacologic treatment. METHODS:The study identified patients with untreated OUD during a treatment episode at a large urban ED. The study randomly assigned three hundred participants in 1:1 ratio to receive SBCM or screening, assessment, and referral (SAR) to OUD treatment. Those assigned to SBCM received up to six sessions of SBCM with the primary goal of linkage to treatment. Primary outcomes were initiation of treatment and engagement in pharmacotherapy for OUD. The study defined a "successful outcome" for opioid use as a 3-month urine negative for illicit opioids and no more than 2 days of self-reported opioid misuse in the 4 weeks prior to the 3-month interview. RESULTS:Rates of treatment initiation were not significantly different in the SBCM and SAR groups (57.4% vs. 49.7%, respectively, p > 0.05), nor did engagement in pharmacotherapy differ significantly between groups (p > 0.05). During the 90 days following the index ED visit, SBCM and SAR participants engaged in pharmacotherapy for a mean of 21.8% (SD = 35.1%) versus 17.7% (SD = 31.0%) of days, respectively. Likewise, no significant difference occurred between groups in rates of "successful opioid use outcome" as defined a priori (p > 0.05), although self-reported opioid use over the entire 6-month follow-up period was lower in the SBCM group (10.8 vs. 13.4 days/month, p = 0.042). CONCLUSIONS:SBCM-ED did not improve OUD treatment initiation and engagement in this ED study. Although these findings do not necessarily generalize to all EDs, other approaches, such as direct referral or initiation of treatment in the ED, have considerable empirical support, and should be implemented where they are feasible.

BACKGROUND:Risk of relapse within the first months after alcohol use disorder (AUD) interventions is substantial among older adults. For this vulnerable group, little information exists on how this risk is associated with residual DSM-5 AUD symptoms after treatment. AIMS/OBJECTIVE:To investigate among older adults who received short-term treatment for DSM-5 AUD (1) the prediction of drinking behaviors and quality of life 12 months after treatment initiation by 6-month DSM-5 AUD symptoms, AUD severity, and AUD remission, and (2) whether these DSM-5 AUD indicators provide prognostic information beyond that gained from 6-month alcohol use (AU) status. METHODS:The international multicenter RCT "ELDERLY-Study" enrolled adults aged 60+ with DSM-5 AUD. We used data from the subsample of 323 German and Danish participants with complete DSM-5 AUD criterion information 6 months after treatment initiation (61% male; mean age = 65.5 years). AU was assessed with Form 90, DSM-5 AUD with the M.I.N.I., and quality of life with the WHOQOL-BREF. Generalized linear models were applied to investigate the associations between 6-month AUD indicators and 12-month AU and quality of life. RESULTS:Independent of AU at 6 months, having 1 (vs. no) residual AUD symptom at 6 months predicted a 12-month "slip," defined as exceeding a blood alcohol concentration of 0.05% at least once during that time (OR: 3.7, 95% CI: 1.5 to 9.0), heavy episodic drinking, and hazardous use (p < 0.05). AUD remission was associated with a lower risk of a "slip" at 12 months (p < 0.05). Failed reduction/cessation was associated with poorer physical health (Coef.: -0.4, 95% CI -0.7 to -0.1). CONCLUSION/CONCLUSIONS:For older adults, residual AUD symptoms in the first months after short-term treatment predict problematic AU outcomes during the first 12 months after treatment entry. Thus, residual symptoms should be addressed in this patient population during posttreatment screenings.

Psychedelic substances have been central to religious and shamanic healing practices of various cultures for generations. More recently, in western medicine, psychedelic substances have demonstrated promise in the treatment of various mental health indications. A growing evidence base supports not only the therapeutic potential of psychedelic-assisted psychotherapy, but also the importance of integrating spiritual aspects of psychedelic experiences into the traditional therapeutic process. Psilocybin, a classic psychedelic, is a serotonergic hallucinogen that can elicit profound spiritual experiences even in the research setting. Our group is currently conducting a randomized controlled trial exploring the therapeutic potential of psilocybin-assisted psychotherapy for alcohol dependence. Over the course of the trial, many individuals have reported experiences that take a variety of forms, including spiritual insights, beatific visions, and communion with the Divine. Here we present three case studies of experiences involving communion with a deceased loved one, with a holy figure, and with the Divine from our clinical trial. These cases have been selected to illustrate the diverse nature of the spiritual experiences observed in this clinical trial, and to also explore elements of spiritual care that may be supportive in the psychotherapeutic process during and after the medication experiences. Should psychedelic medicine continue to show treatment promise in clinical trial stages, there is a strong possibility that these medicines will become an integral part of psychotherapy, which will require integration of direct spiritual experiences and spiritual care into the healing process. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P < 0.0001, d = 0.91) and to significantly decrease the SDS total score (P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was -24.4 (s.d. 11.6) in the MDMA group and -13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation.

BACKGROUND:Studies have found that reductions in World Health Organization (WHO) drinking risk levels may be a stable outcome of treatment for alcohol use disorder (AUD) and associated with functional improvements. The aim of this study was to investigate whether posttreatment reductions in WHO drinking risk levels are stable over time among older adults and associated with a decrease in consequences of drinking and AUD symptoms and improved quality of life. METHODS:Participants. Individuals 60+ years old, suffering from DSM-5 AUD (n = 693), and seeking outpatient treatment. MEASUREMENTS:WHO drinking risk levels, prior to treatment and at all follow-up points up to 1 year after treatment start, were assessed with Form 90. Outcomes at follow-up included consequences of drinking (Drinker Inventory of Consequences), quality of life (WHOQOL-BREF), and DSM-5 AUD symptoms (Mini International Neuropsychiatric Interview). Logistic regression and linear mixed models were used to examine the probability of maintaining risk-level reductions at follow-up and the association between risk-level reductions and outcomes, respectively. RESULTS:Reductions in risk levels were maintained over time (at least 1 level: OR 5.39, 95% CI 3.43, 8.47; at least 2 levels: OR 9.30, 95% CI 6.14, 14.07). Reductions were associated with reduced consequences of drinking and number of AUD symptoms, and minor, but statistically significant, improvements in quality of life. CONCLUSIONS:Maintaining reductions in WHO risk levels appears achievable for older adults seeking treatment for AUD. The small reduction of AUD symptoms and improvement of quality of life indicates that these reductions may not be adequate as the only treatment goal.

BACKGROUND:Relatively little is known about the prognostic value of comorbid mental disorders in alcohol use disorder (AUD) treatment for older adults (OA). AIMS/OBJECTIVE:This article aimed to investigate 1) the impact of current unipolar mood and anxiety disorders in AUD treatment success in OA, 2) the timing of this putative comorbidity impact over six months, and 3) the role of treatment length in comorbidity effects. METHODS:We analyzed baseline and one-, three-, and six-month follow-up data from the international multicenter RCT "ELDERLY-Study" (baseline n = 693, median age: 64.0 years) using mixed effects regression models. In adults aged 60+ with DSM-5 AUD "ELDERLY" compared outpatient motivational enhancement therapy (MET, four sessions) with outpatient MET plus community reinforcement approach for seniors (MET & CRA-S; up to 12 sessions). Aiming for abstinence or minimal alcohol use (AU), both conditions included CBT-elements. We assessed AU with Form 90, and mental disorders with the Mini International Neuropsychiatric Interview (M.I.N.I.). RESULTS:Mood-related disorders were associated with more drinks per day at baseline and greater reductions in drinks per day at one and six months (main effect mood disorder: Coef. 2.1, 95% CI 0.6-3.6; one month interaction effect: Coef. -1.9, 95% CI -3.3- -0.5; six months interaction effect: Coef. -2.1, 95% CI -3.5 - -0.6). These results were replicated within MET & CRA-S but not within MET. CONCLUSION/CONCLUSIONS:Comorbid mental disorders had modest effects on short-term outpatient treatment outcomes. OA with AUD and unipolar mood-related disorders may profit from short interventions based on motivational interviewing and CBT-elements. ClinicalTrials.gov:NCT02084173.

BACKGROUND:As the USA grapples with an opioid epidemic, medical emergency departments (EDs) have become a critical setting for intervening with opioid-dependent patients. Brief interventions designed to bridge the gap from acute ED care to longer-term treatment have shown limited efficacy for this population. Strength-based case management (SBCM) has shown strong effects on treatment linkage among patients with substance use disorders in other healthcare settings. This study aimed to investigate whether SBCM is an effective model for linking opioid-dependent ED patients with addiction treatment and pharmacotherapy. Here, we describe the implementation and challenges of adapting SBCM for the ED (SBCM-ED). Study rationale, design, and baseline characteristics are also described. METHODS:This study compared the effects of SBCM-ED to screening, assessment, and referral alone (SAR) on treatment linkage, substance use, and functioning. We recruited participants from a public hospital in NYC. Working alliance between case managers and participants and the feasibility of SBCM implementation were evaluated. Baseline data from the randomized sample were analyzed for group equivalency. Outcomes analyses are forthcoming. RESULTS:Three hundred adult participants meeting DSM-IV criteria for opioid dependence were randomly assigned to either SBCM, in which they received a maximum of six case management sessions within 90 days of enrollment, or SAR, in which they received a comprehensive referral list and pamphlet outlining drug use consequences. No significant differences were found between groups at baseline on demographic or substance use characteristics. All SAR participants and 92.6% of SBCM-ED participants initiated their assigned intervention. Over half of SBCM-ED first sessions occurred in the ED on the day of enrollment. Case managers developed a strong working alliance with SBCM-ED participants after just one session. CONCLUSION/CONCLUSIONS:Interventions that exceed SBIRT were accepted by an opioid-dependent patient population seen in an urban medical ED. At the time of study funding, this trial was one of the first to focus specifically on this population in this challenging setting. The successful implementation of SBCM demonstrates its adaptability to the ED and may serve as a potential model for EDs seeking to adopt an intervention that overcomes the barrier between the ED encounter and more intensive treatment. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT02586896 . Registered on 27 October 2015.

BACKGROUND:We reanalyzed a multisite 26-week randomized double-blind placebo-controlled clinical trial of 600 mg twice-a-day Gabapentin Enacarbil Extended-Release (GE-XR), a gabapentin prodrug, designed to evaluate safety and efficacy for treating alcohol use disorder. In the original analysis (n = 338), published in 2019, GE-XR did not differ from placebo. Our aim is to advance precision medicine by identifying likely responders to GE-XR from the trial data and to determine for likely responders if GE-XR is causally superior to placebo. METHODS:The primary outcome measure in the reanalysis is the reduction from baseline of the number of heavy drinking days (ΔHDD). Baseline features including measures of alcohol use, anxiety, depression, mood states, sleep, and impulsivity were used in a random forest (RF) model to predict ΔHDD to treatment with GE-XR based on those assigned to GE-XR. The resulting RF model was used to obtain predicted outcomes for those randomized to GE-XR and counterfactually to those randomized to placebo. Likely responders to GE-XR were defined as those predicted to have a reduction of 14 days or more. Tests of causal superiority of GE-XR to placebo were obtained for likely responders and for the whole sample. RESULTS:For likely responders, GE-XR was causally superior to placebo (p < 0.0033), while for the whole sample, there was no difference. Likely responders exhibited improved outcomes for the related outcomes of percent HDD and drinks per week. Compared with unlikely responders, at baseline likely responders had higher HDDs; lower levels of anxiety, depression, and general mood disturbances; and higher levels of cognitive and motor impulsivity. CONCLUSIONS:There are substantial causal benefits of treatment with GE-XR for a subset of patients predicted to be likely responders. The likely responder statistical paradigm is a promising approach for analyzing randomized clinical trials to advance personalized treatment.

Impairment in cognitive control in alcohol use disorder (AUD) contributes to difficulty controlling alcohol use and, in many populations, difficulties with emotion regulation. However, the most reliable and robust marker of clinically-relevant deficits in cognitive control in AUD is unclear. Our aims were to measure relationships between BOLD signal during a Stroop task and AUD severity and change in BOLD signal and change in drinking over three weeks. We also aimed to explore the relationships between BOLD signal and subjective negative affect. Thirty-three individuals with AUD underwent a multisensory Stroop task during functional magnetic resonance imaging (fMRI), as well as a battery of neuropsychological tests and self-report assessments of negative affect and AUD severity. Greater activation in temporal gyrus and cerebellum during incongruent trials compared to congruent trials was observed, and percent signal change (incongruent minus congruent) in both clusters was positively correlated with AUD severity and self-reported negative affect. Neuropsychological task performance and self-reported impulsivity were not highly correlated with AUD severity. Hierarchical regression analyses indicated that percent signal change (incongruent minus congruent) in cerebellum was independently associated with negative affect after controlling for recent and chronic drinking. In a subset of individuals (n = 23) reduction in cerebellar percent signal change (incongruent minus congruent) was correlated with increases in percent days abstinent over 3 weeks. BOLD activation during this Stroop task may therefore be an important objective marker of AUD severity and negative affect. The potential importance of the cerebellum in emotion regulation and AUD severity is highlighted.