Faculty Bibliography

OBJECTIVE:This study is a secondary descriptive analysis that explores and compares the cognitive profiles of adults entering treatment at geographically diverse community-based substance use disorder treatment facilities. METHODS:Performance on cognitive measures at baseline was compared across 5 primary substance subgroups of individuals (alcohol = 104; cocaine = 102; stimulants = 69; opioids = 108; marijuana = 114) enrolled in a web-based psychosocial treatment study conducted within the National Drug Abuse Treatment Clinical Trials Network. MicroCog subtests were used to assess cognitive domains of attention and mental control, reasoning and cognitive flexibility, and spatial processing. RESULTS:The average age of onset for a substance use disorder was early to mid-20s, with marijuana users reporting the earliest age of onset (mean 19.9, SD 7.5) and stimulant users reporting the latest (mean 25.2, SD 9.9). Among the total sample, half (49.7%) demonstrated impairment in cognitive flexibility and reasoning, and over one-third (37.3%) had impairment in verbal learning and memory. Stimulant (37.68%) and cocaine (34.31%) users showed significantly greater clinical impairment in attention and mental control compared with alcohol users (17.31%) and opioid (21.30%) users (stimulant subgroup only) (χ [4] = 10.97, P = 0.027). Cocaine users showed the greatest overall impairment across total and proficiency subtest scores, although these were not statistically different from other subgroups. CONCLUSIONS:These findings confirmed previous studies, indicating a high prevalence of significant cognitive dysfunction across all substance use categories among treatment-seeking adults, and found that cocaine use appears to be associated with the most impairment. Increasing knowledge of similarities and differences between primary substance subgroups can help guide substance use disorder treatment planning.

Cognitive impairments are associated with poor outcomes when treating cocaine dependent patients, but behavioral interventions to mitigate this impact have not been developed. In this Stage 1A/1B treatment development study, several compensatory strategies (e.g., content repetition, daily logs, diaries, visual presentation) were combined to create a modified cognitive behavioral therapy (M-CBT) for treating cocaine dependence. Initially, a select group of therapists, neuropsychology experts, and patients were asked to provide input on early drafts of the treatment manual and companion patient workbook. After an uncontrolled small trial (N = 15) and two rounds of manual development (Stage 1A), a pilot randomized clinical trial (N = 102) of cocaine dependent outpatients with and without cognitive impairments was conducted (Stage 1B). Participants were randomized to M-CBT (N = 52) or CBT (N = 50). Both treatments were individually delivered over 12 weeks with assessments conducted at baseline, end-of-treatment, and 3-month follow-up. The primary outcome was frequency of cocaine use, measured by number of days used in the prior 7 days. Participants in the two treatment groups did not differ significantly on drug use reduction or retention in treatment. However, among participants who completed at least 9 weeks of treatment, those in M-CBT showed a trend toward greater reduction in cocaine use compared to those in the CBT group. M-CBT is feasible for impaired and nonimpaired cocaine dependent participants. However, M-CBT treatment did not show significant superiority over standard CBT in the present sample. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

BACKGROUND:Attention-deficit hyperactivity disorder (ADHD) is overrepresented among individuals seeking treatment for substance use disorders. We previously reported that treatment with extended release mixed amphetamine salts (MAS-XR) increased abstinence, compared to placebo, among patients with co-occurring ADHD and cocaine dependence. This secondary analysis investigates the temporal relationship between ADHD improvement and cocaine abstinence in the first six weeks of the trial. METHODS:The study was a three-arm, randomized, double-blinded, placebo-controlled, 14-week trial comparing MAS-XR (60 mg or 80 mg daily) versus placebo among 126 participants with ADHD and cocaine dependence. An autoregressive cross-lagged structural equation model was fit and evaluated weekly ADHD improvement (defined as ≥30% reduction in the Adult ADHD Investigator Symptom Rating Scale) and urine-confirmed abstinence over the first six weeks. RESULTS:The proportion of patients with each of the possible overall patterns of response was: ADHD improves before cocaine abstinence: 24%; Cocaine abstinence occurs before ADHD improvement: 12%; ADHD improvement and abstinence occur during the same week: 6%; ADHD improves but abstinence never achieved: 34%; Abstinence achieved but ADHD never improves: 6%; Neither ADHD improvement nor abstinence: 18%. A significant cross-lagged association was found; subjects with ADHD improvement at week 2 had significantly higher odds of cocaine abstinence at week 3 (p = .014). CONCLUSION:When treating co-occurring ADHD and cocaine dependence with stimulant medication, abstinence is most likely preceded by improvement in ADHD, which tends to occur early with medication treatment. Other observed temporal patterns suggest the potential complexity of the relationship between ADHD and cocaine dependence.

BACKGROUND:Previous studies have shown that repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex may serve as a potential treatment for cocaine use disorder (CUD), which remains a public health problem that is refractory to treatment. The goal of this pilot study was to investigate the effect of rTMS on cocaine self-administration in the laboratory. In the self-administration sessions, CUD participants chose between cocaine and an alternative reinforcer (money) in order to directly measure cocaine-seeking behavior. The rTMS was delivered with the H7 coil, which provides stimulation to the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). These brain regions were targeted based on previous imaging studies demonstrating alterations in their activation and connectivity in CUD. METHODS:Volunteers with CUD were admitted to an inpatient unit for the entire study and assigned to one of three rTMS groups: high frequency (10 Hz), low frequency (1 Hz), and sham. Six participants were included in each group and the rTMS was delivered on weekdays for 3 weeks. The cocaine self-administration sessions were performed at three time points: at baseline (pre-TMS, session 1), after 4 days of rTMS (session 2), and after 13 days of rTMS (session 3). During each self-administration session, the outcome measure was the number of choices for cocaine. RESULTS: = 0.02), where the choices for cocaine decreased between sessions 2 and 3 in the high frequency group. There was no effect of rTMS on cocaine self-administration in the low frequency or sham groups. CONCLUSION/CONCLUSIONS:Taken in the context of the existing literature, these results contribute to the data showing that high frequency rTMS to the prefrontal cortex may serve as a potential treatment for CUD.

OBJECTIVES:To estimate the costs of providing extended-release injectable naltrexone (XR-NTX) and buprenorphine-naloxone (BUP-NX) following inpatient detoxification using data derived from a multisite randomized controlled trial at 8 US community-based treatment programs. STUDY DESIGN:Cost data were collected for 3 intervention phases: program start-up, inpatient detoxification, and up to 24 weeks of medication induction and management visits (post detoxification). Cost analyses were from the healthcare sector perspective (2015 US$); patient costs are also reported. METHODS:We conducted site visits, administered a cost survey to treatment programs, and analyzed study data on medication and services utilization. Nationally representative sources were used to estimate unit costs. Uncertainty was evaluated in sensitivity analyses. RESULTS:Mean start-up costs were $1071 per program for XR-NTX and $828 per program for BUP-NX. Mean costs per participant were $5416 for XR-NTX (57% detoxification, 37% medication, 3% provider, 3% patient) and $4148 for BUP-NX (64% detoxification, 12% medication, 10% provider, 14% patient). Total cost per participant ranged by site from $2979 to $8963 for XR-NTX and from $2521 to $6486 for BUP-NX. CONCLUSIONS:For treatment providers, offering XR-NTX and/or BUP-NX as part of existing detoxification treatment modalities generates modest costs in addition to the costs of detoxification, which vary substantially among the 8 sites. From the patient's perspective, the costs associated with medication management visits may be a barrier for some individuals considering these treatments.

BACKGROUND AND OBJECTIVES:Substance use disorders are associated with lower cognitive functioning, and this impairment is associated with poorer outcomes. The Therapeutic Education System (TES) is an internet-based psychosocial intervention for substance use disorders that may provide enhanced treatment for individuals with cognitive deficits. This secondary analysis investigates the association between cognitive functioning and treatment outcomes in a large (N = 507) randomized controlled effectiveness trial of TES compared to treatment-as-usual conducted within outpatient programs in the National Drug Abuse Treatment Clinical Trials Network. METHODS:All participants completed a computer-based cognitive assessment (Microcog™ short version) at baseline. Scores on subtests of attention, reasoning, and spatial perception were tested as moderators of the treatment effect on abstinence and retention at the end of the 12-week treatment phase using mixed effects logistic regression. RESULTS:Cognitive functioning was not found to be a moderator of treatment on abstinence or retention. Post-hoc analysis of the main effect of cognitive functioning on retention and abstinence found impaired reasoning and cognitive flexibility were associated with lower retention. There were no other main effects of cognitive functioning on retention or abstinence. CONCLUSIONS:The benefit of internet delivered treatment over standard care was unchanged across a range of cognitive functioning. Consistent with previous research, mild to moderate impairment in reasoning and cognitive flexibility were associated with lower retention across both treatment arms. SCIENTIFIC SIGNIFICANCE:An internet-delivered cognitive behavioral intervention for substance use disorders, TES, is equally effective across a spectrum of cognitive functioning among diverse patients. (Am J Addict 2018;27:509-515).

BACKGROUND:Despite increasing opioid overdose mortality, problems persist in the availability and quality of treatment for opioid use disorder (OUD). Three FDA-approved medications (methadone, buprenorphine, and naltrexone) have high quality evidence supporting their use, but most individuals with OUD do not receive them and many experience relapse following care episodes. Developing and organizing quality measures under a unified framework such as a Cascade of Care could improve system level practice and treatment outcomes. In this context, a review was performed of existing quality measures relevant to the treatment of OUD and the literature assessing the utility of these measures in community practice. METHODS:Systematic searches of two national quality measure clearinghouses (National Quality Forum and Agency for Healthcare Research and Quality) were performed for measures that can be applied to the treatment of OUD. Measures were categorized as structural, process, or outcome measures. Second stage searches were then performed within Ovid/Medline focused on published studies investigating the feasibility, reliability, and validity of identified measures, predictors of their satisfaction, and related clinical outcomes. RESULTS:Seven quality measures were identified that are applicable to the treatment of OUD. All seven were process measures that assess patterns of service delivery. One recently approved measure addresses retention in medication-assisted treatment for patients with OUD. Twenty-nine published studies were identified that evaluate the quality measures, primarily focused on initiation and engagement in care for addiction treatment generally. Most measures and related studies do not specifically incorporate the evidence base for the treatment of OUD or assess patient level outcomes such as overdose. CONCLUSION:Despite considerable progress, gaps exist in quality measures for OUD treatment. Development of a unified quality measurement framework such as an OUD Treatment Cascade will require further elaboration and refinement of existing measures across populations and settings. Such a framework could form the basis for applying strategies at clinical, organizational, and policy levels to expand access to quality care and reduce opioid-related mortality.

IMPORTANCE:Buprenorphine treatment for opioid use disorder may be improved by sustained-release formulations. OBJECTIVE:To determine whether treatment involving novel weekly and monthly subcutaneous (SC) buprenorphine depot formulations is noninferior to a daily sublingual (SL) combination of buprenorphine hydrochloride and naloxone hydrochloride in the treatment of opioid use disorder. DESIGN, SETTING, AND PARTICIPANTS:This outpatient, double-blind, double-dummy randomized clinical trial was conducted at 35 sites in the United States from December 29, 2015, through October 19, 2016. Participants were treatment-seeking adults with moderate-to-severe opioid use disorder. INTERVENTIONS:Randomization to daily SL placebo and weekly (first 12 weeks; phase 1) and monthly (last 12 weeks; phase 2) SC buprenorphine (SC-BPN group) or to daily SL buprenorphine with naloxone (24 weeks) with matched weekly and monthly SC placebo injections (SL-BPN/NX group). MAIN OUTCOMES AND MEASURES:Primary end points tested for noninferiority were response rate (10% margin) and the mean proportion of opioid-negative urine samples for 24 weeks (11% margin). Responder status was defined as having no evidence of illicit opioid use for at least 8 of 10 prespecified points during weeks 9 to 24, with 2 of these at week 12 and during month 6 (weeks 21-24). The mean proportion of samples with no evidence of illicit opioid use (weeks 4-24) evaluated by a cumulative distribution function (CDF) was an a priori secondary outcome with planned superiority testing if the response rate demonstrated noninferiority. RESULTS:A total of 428 participants (263 men [61.4%] and 165 women [38.6%]; mean [SD] age, 38.4 [11.0] years) were randomized to the SL-BPN/NX group (n = 215) or the SC-BPN group (n = 213). The response rates were 31 of 215 (14.4%) for the SL-BPN/NX group and 37 of 213 (17.4%) for the SC-BPN group, a 3.0% difference (95% CI, -4.0% to 9.9%; P < .001). The proportion of opioid-negative urine samples was 1099 of 3870 (28.4%) for the SL-BPN/NX group and 1347 of 3834 (35.1%) for the SC-BPN group, a 6.7% difference (95% CI, -0.1% to 13.6%; P < .001). The CDF for the SC-BPN group (26.7%) was statistically superior to the CDF for the SL-BPN/NX group (0; P = .004). Injection site adverse events (none severe) occurred in 48 participants (22.3%) in the SL-BPN/NX group and 40 (18.8%) in the SC-BPN group. CONCLUSIONS AND RELEVANCE:Compared with SL buprenorphine, depot buprenorphine did not result in an inferior likelihood of being a responder or having urine test results negative for opioids and produced superior results on the CDF of no illicit opioid use. These data suggest that depot buprenorphine is efficacious and may have advantages. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT02651584.