Kinetic principles of ParA2-ATP cycling guide dynamic subcellular localizations in Vibrio cholerae.

Dynamic protein gradients are exploited for the spatial organization and segregation of replicated chromosomes. However, mechanisms of protein gradient formation and how that spatially organizes chromosomes remain poorly understood. Here, we have determined the kinetic principles of subcellular localizations of ParA2 ATPase, an essential spatial regulator of chromosome 2 segregation in the multichromosome bacterium, Vibrio cholerae. We found that ParA2 gradients self-organize in V. cholerae cells into dynamic pole-to-pole oscillations. We examined the ParA2 ATPase cycle and ParA2 interactions with ParB2 and DNA. In vitro, ParA2-ATP dimers undergo a rate-limiting conformational switch, catalysed by DNA to achieve DNA-binding competence. This active ParA2 state loads onto DNA cooperatively as higher order oligomers. Our results indicate that the midcell localization of ParB2-parS2 complexes stimulate ATP hydrolysis and ParA2 release from the nucleoid, generating an asymmetric ParA2 gradient with maximal concentration toward the poles. This rapid dissociation coupled with slow nucleotide exchange and conformational switch provides for a temporal lag that allows the redistribution of ParA2 to the opposite pole for nucleoid reattachment. Based on our data, we propose a 'Tug-of-war' model that uses dynamic oscillations of ParA2 to spatially regulate symmetric segregation and positioning of bacterial chromosomes.

Reconstitutions of plasmid partition systems and their mechanisms.

Bacterial plasmid and chromosome segregation systems ensure that genetic material is efficiently transmitted to progeny cells. Cell-based studies have shed light on the dynamic nature and the molecular basis of plasmid partition systems. In vitro reconstitutions, on the other hand, have proved to be an invaluable tool for studying the minimal components required to elucidate the mechanism of DNA segregation. This allows us to gain insight into the biological and biophysical processes that enable bacterial cells to move and position DNA. Here, we review the reconstitutions of plasmid partition systems in cell-free reactions, and discuss recent work that has begun to challenge long standing models of DNA segregation in bacteria.

Examining multi-session brief intervention for substance use in primary care: research methods of a randomized controlled trial.

BACKGROUND: Brief interventions such as Screening, a single session of Brief Intervention, and Referral to Treatment (SBIRT) have shown mixed effectiveness in primary care. However, there are indications that multi-session brief interventions may demonstrate more consistently positive outcomes, and perhaps a more intensive approach would be of benefit in addressing substance use in primary care. This study compared the effectiveness of SBIRT with a single BI session (BI/RT) to a multi-session brief-treatment intervention (BI/RT+) in primary care. We also developed easy-to-use, evidence-based materials to assist clinicians in delivering these interventions. METHODS/DESIGN: This study was conducted in three Federally Qualified Healthcare Centers (FQHCs). A total of 10,935 patients were screened, and 600 individuals were recruited. The sample was primarily Black/African American (82 %) with a mean age of 40. Patients who attended a healthcare appointment were screened for substance use via the AUDIT and DAST. Patients were eligible for the study if they scored 8 or higher on the AUDIT, were using only marijuana and scored 2 or higher on the DAST, or were using other illicit drugs and scored 1 or higher on the DAST. Participants were randomly assigned to receive one-session BI/RT, or two to six sessions of brief intervention that incorporated elements of motivational enhancement therapy and cognitive-behavioral therapy (BI/RT+). Both interventions were delivered by behavioral health consultants at the FQHCs. Participants completed follow-up assessments every 3 months for 1 year. Primary outcome variables included substance use treatment sessions attended and days of substance use. Secondary outcomes included measures of health, employment, legal, and psychiatric functioning and HIV risk behaviors. Additionally, we will conduct an economic evaluation examining cost-effectiveness and will analyze outcomes from a process evaluation examining patient and provider experiences. DISCUSSION: The ability of brief interventions to impact substance use has great potential, but research findings have been mixed. By conducting a large-scale randomized controlled trial in real-world health centers, this study will answer important questions about the effectiveness of expanded BIs for patients who screen positive for risky substance use in primary care. Trial registration NCT01751672.

Implementation of a Brief Treatment Counseling Toolkit in Federally Qualified Healthcare Centers: Patient and Clinician Utilization and Satisfaction.

INTRODUCTION: The need to integrate behavioral health care within medical settings is widely recognized, and integrative care approaches are associated with improved outcomes for a range of disorders. As substance use treatment integration efforts expand within primary care settings, training behavioral health providers in evidence-based brief treatment models that are cost-effective and easily fit within the medical flow is essential. METHODS: Guided by principles drawn from Diffusion of Innovations theory (Rogers, 2003) and the Consolidated Framework of Implementation Research (Damschroder et al., 2009), we adapted elements of Motivational Enhancement Therapy, cognitive-behavioral therapy, and 12-step facilitation into a brief counseling toolkit. The toolkit is a menu driven assortment of 35 separate structured clinical interventions that each include client takeaway resources to reinforce brief clinical contacts. We then implemented this toolkit in the context of a randomized clinical trial in three Federally Qualified Healthcare Centers. Behavioral Health Consultants (BHCs) used a pre-screening model wherein 10,935 patients received a brief initial screener, and 2011 received more in-depth substance use screening. Six hundred patients were assigned to either a single session brief intervention or an expanded brief treatment encompassing up to five additional sessions. We conducted structured interviews with patients, medical providers, and BHCs to obtain feedback on toolkit implementation. RESULTS: On average, patients assigned to brief treatment attended 3.29 sessions. Fifty eight percent of patients reported using most or all of the educational materials provided to them. Patients assigned to brief treatment reported that the BHC sessions were somewhat more helpful than did patients assigned to a single session brief intervention (p=.072). BHCs generally reported that the addition of the toolkit was helpful to their work in delivering screening and brief treatment. DISCUSSION: This work is significant because it provides support to clinicians in delivering evidence-based brief interventions and has been formatted into presentation styles that can be presented flexibly depending on patient need.

The RoadMAP Relapse Prevention Group Counseling Toolkit™: counselor adherence and competence outcomes.

Training counselors in empirically supported treatments (ESTs) far exceeds the ever decreasing resources of community-based treatment agencies. The purpose of this study was to examine outpatient substance abuse group counselors' (n=19) adherence and competence in communicating and utilizing concepts associated with empirically-supported relapse prevention treatment following a brief multimedia toolkit (RoadMAP Toolkit™) training. Moderate or large baseline to post-training effect sizes for counselor adherence to toolkit content were identified for 13 of 21 targeted behaviors (overall d range=.06-2.85) with the largest gains on items measuring active skill practice. Post-training adherence gains were largely maintained at the 6-month follow-up, although no statistically significant improvements were identified over time for counselor competence. This study provides important preliminary support for using a multi-media curriculum approach to increase empirically-supported relapse prevention skills among group counselors. Future research should focus on finding ways to improve counselor skill level and to determine the impact of the Toolkit on client outcomes.

"Old dogs" and new skills: how clinician characteristics relate to motivational interviewing skills before, during, and after training.

OBJECTIVE: The relationships between the occupational, educational, and verbal-cognitive characteristics of health care professionals and their motivational interviewing (MI) skills before, during, and after training were investigated. METHOD: Fifty-eight community-based addiction clinicians (M = 42.1 years, SD = 10.0; 66% Female) were assessed prior to enrolling in a 2-day MI training workshop and being randomized to one of three post-workshop supervision programs: live supervision via tele-conferencing (TCS), standard tape-based supervision (Tape), or workshop training alone. Audiotaped sessions with clients were rated for MI skillfulness with the Motivational Interviewing Treatment Integrity (MITI) coding system v 2.0 at pre-workshop and 1, 8, and 20 weeks post-workshop. Correlation coefficients and generalized linear models were used to test the relationships between clinician characteristics and MI skill at each assessment point. RESULTS: Baseline MI skill levels were the most robust predictors of pre- and post-supervision performances. Clinician characteristics were associated with MI Spirit and reflective listening skill throughout training and moderated the effect of post-workshop supervision method on MI skill. TCS, which provided immediate feedback during practice sessions, was most effective for increasing MI Spirit and reflective listening among clinicians with no graduate degree and stronger vocabulary performances. Tape supervision was more effective for increasing these skills among clinicians with a graduate degree. Further, TCS and Tape were most likely to enhance MI Spirit among clinicians with low average to average verbal and abstract reasoning performances. CONCLUSIONS: Clinician attributes influence the effectiveness of methods used to promote the acquisition of evidence-based practices among community-based practitioners.

Training substance abuse clinicians in motivational interviewing using live supervision via teleconferencing.

OBJECTIVE: Training through traditional workshops is relatively ineffective for changing counseling practices. Teleconferencing supervision (TCS) was developed to provide remote, live supervision for training motivational interviewing (MI). METHOD: Ninety-seven drug treatment counselors completed a 2-day MI workshop and were randomized to live supervision via teleconferencing (TCS; n = 32), standard tape-based supervision (tape; n = 32), or workshop alone (workshop; n = 33). Supervision conditions received 5 weekly supervision sessions at their sites using actors as standard patients. Sessions with clients were rated for MI skill with the Motivational Interviewing Treatment Integrity (MITI) Coding System pre-workshop and 1, 8, and 20 weeks post-workshop. Mixed-effects linear models were used to test training condition on MI skill at 8 and 20 weeks. RESULTS: TCS scored better than workshop on the MITI for spirit (mean difference = 0.76; p < .0001; d = 1.01) and empathy (mean difference = 0.68; p < .001; d = 0.74). TCS was superior to workshop in reducing MI non-adherence and was superior to workshop and tape in increasing reflection to question ratio. Tape was superior to TCS in increasing complex reflections. Percentage of counselors meeting proficiency differed significantly between training conditions for the most stringent threshold (spirit and empathy scores ≥ 6). CONCLUSIONS: TCS shows promise for promoting new counseling behaviors following participation in workshop training. However, further work is needed to improve supervision methods to bring more clinicians to high levels of proficiency and facilitate dissemination of evidence-based practices.

Study protocol: a randomized controlled trial of a computer-based depression and substance abuse intervention for people attending residential substance abuse treatment.

BACKGROUND: A large proportion of people attending residential alcohol and other substance abuse treatment have a co-occurring mental illness. Empirical evidence suggests that it is important to treat both the substance abuse problem and co-occurring mental illness concurrently and in an integrated fashion. However, the majority of residential alcohol and other substance abuse services do not address mental illness in a systematic way. It is likely that computer delivered interventions could improve the ability of substance abuse services to address co-occurring mental illness. This protocol describes a study in which we will assess the effectiveness of adding a computer delivered depression and substance abuse intervention for people who are attending residential alcohol and other substance abuse treatment. METHODS/DESIGN: Participants will be recruited from residential rehabilitation programs operated by the Australian Salvation Army. All participants who satisfy the diagnostic criteria for an alcohol or other substance dependence disorder will be asked to participate in the study. After completion of a baseline assessment, participants will be randomly assigned to either a computer delivered substance abuse and depression intervention (treatment condition) or to a computer-delivered typing tutorial (active control condition). All participants will continue to complete The Salvation Army residential program, a predominantly 12-step based treatment facility. Randomisation will be stratified by gender (Male, Female), length of time the participant has been in the program at the commencement of the study (4 weeks or less, 4 weeks or more), and use of anti-depressant medication (currently prescribed medication, not prescribed medication). Participants in both conditions will complete computer sessions twice per week, over a five-week period. Research staff blind to treatment allocation will complete the assessments at baseline, and then 3, 6, 9, and 12 months post intervention. Participants will also complete weekly self-report measures during the treatment period. DISCUSSION: This study will provide comprehensive data on the effect of introducing a computer delivered, cognitive behavioral therapy based co-morbidity treatment program within a residential substance abuse setting. If shown to be effective, this intervention can be disseminated within other residential substance abuse programs. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000618954.

Developing an evidence-based, multimedia group counseling curriculum toolkit.

Training community-based addiction counselors in empirically supported treatments (ESTs) far exceeds the ever-decreasing resources of publicly funded treatment agencies. This feasibility study describes the development and pilot testing of a group counseling toolkit (an approach adapted from the education field) focused on relapse prevention (RP). When counselors (N = 17) used the RP toolkit after 3 hours of training, their content adherence scores on "coping with craving" and "drug refusal skills" showed significant improvement, as indicated by very large effect sizes (Cohen's d = 1.49 and 1.34, respectively). Counselor skillfulness, in the "adequate-to-average" range at baseline, did not change. Although this feasibility study indicates some benefit to counselor EST acquisition, it is important to note that the impact of the curriculum on client outcomes is unknown. Because a majority of addiction treatment is delivered in group format, a multimedia curriculum approach may assist counselors in applying ESTs in the context of actual service delivery.

Long-acting injectable versus oral naltrexone maintenance therapy with psychosocial intervention for heroin dependence: a quasi-experiment.

OBJECTIVE: To conduct a quasi-experimental comparison of early clinical outcomes between injectable, sustained-release, depot naltrexone formulation versus oral naltrexone maintenance therapy in individuals with opiate dependence. METHOD: Early retention in treatment and urine-confirmed opiate use in the first 8 weeks postdetoxification were compared between patients (diagnosed as opiate-dependent according to DSM-IV criteria) participating in 2 concurrently run randomized clinical trials of oral (n = 69; patients treated from September 1999 to May 2002) and long-acting injectable (n = 42; patients treated from November 2000 to June 2003) naltrexone maintenance therapy with psychosocial therapy. RESULTS: Long-acting injectable naltrexone produced significantly better outcome than oral naltrexone on days retained in treatment (F(1,106) = 6.49, P = .012) and for 1 measure of opiate use (F(1,106) = 5.26, P = .024); other measures were not significantly different, but differences were in the same direction. In subanalyses, there were interaction effects between baseline heroin use severity and type of treatment. In subanalyses, heroin users with more severe baseline use showed better retention with oral naltrexone maintenance therapy combined with intensive psychotherapy (behavioral naltrexone therapy) as compared to retention shown by severe heroin users treated with long-acting naltrexone injections combined with standard cognitive-behavioral therapy (χ²(1)= 9.31, P = .002); less severe heroin users evidenced better outcomes when treated with long-acting injectable naltrexone. CONCLUSIONS: This quasi-experimental analysis provides tentative indications of superior outcomes for heroin-dependent patients treated with long-acting injectable naltrexone compared to oral naltrexone. The finding that heroin users with more severe baseline use achieved better outcomes with oral naltrexone is most probably attributable to the intensive nature of the psychosocial treatments provided and points to the opportunity for continued research in augmenting injectable naltrexone with psychosocial strategies to further improve outcome, especially in individuals with more severe use. The results should be considered exploratory given the quasi-experimental nature of the study.

Feasibility and effectiveness of computer-based therapy in community treatment.

Computerized therapy approaches may expand the reach of evidence-based treatment; however, it is unclear how to integrate these therapies into community-based treatment. We conducted a two-phase pilot study to explore (a) whether clients' use of the Therapeutic Education System (TES), a Web-based community reinforcement approach (CRA) learning program, would benefit them in the absence of counselor support and (b) whether counselors and clients would use the TES in the absence of tangible research-based reinforcement. In Phase 1, clients in the TES condition (n = 14) demonstrated large improvements in knowledge, F(1, 20) = 8.90, p = .007, d = 1.05, and were significantly more likely to select CRA style coping responses, F (1, 20) = 11.95, p = .002, d = 1.16, relative to the treatment-as-usual group (n = 14). We also detected small, nonsignificant, between-group effects indicating TES decreased cocaine use during treatment. In Phase 2, counselors referred only around 10% of their caseload to the TES, and the modal number of completed modules in the absence of tangible reinforcement was three. Computer-based therapy approaches are viable in community-based treatment but must be integrated with incentive systems to ensure engagement.

Barriers to Implementing Individualized Substance Abuse Treatment: Qualitative Findings from the CASPAR Replication Studies.

Problem-to-services matching is critical to patient-centered care. Further, the extent to which substance abuse treatment is individualized to meet specific client needs is a key predictor of success and represents "best practice" in substance abuse treatment. The CASPAR Resource Guide, an electronic database of local free and low-cost services, is an evidence-based tool designed to help counselors easily and quickly provide offsite referrals to services not available in most community treatment programs to increase problem-to-service matching. This paper examines system-level barriers to using the CASPAR Resource Guide among 30 counselors and 21 site directors across 16 sites in two different studies. Results from qualitative implementation analyses found that key program components needed to support the implementation of this evidence-based practice (e.g., individualized treatment planning, individual treatment sessions, and individual counselor supervision) were lacking, which jeopardized successful adoption of the CASPAR research interventions and prompted a redesign of the studies in order to enhance each program's ability to support individualized care.

Intermittent marijuana use is associated with improved retention in naltrexone treatment for opiate-dependence.

Naltrexone is a theoretically promising alternative to agonist substitution treatment for opioid dependence, but its effectiveness has been severely limited by poor adherence. This study examined, in an independent sample, a previously observed association between moderate cannabis use and improved retention in naltrexone treatment. Opioid dependent patients (N = 63), admitted for inpatient detoxification and induction onto oral naltrexone, and randomized into a six-month trial of intensive behavioral therapy (Behavioral Naltrexone Therapy) versus a control behavioral therapy (Compliance Enhancement), were classified into three levels of cannabis use during treatment based on biweekly urine toxicology: abstinent (0% cannabis positive urine samples); intermittent use (1% to 79% cannabis positive samples); and consistent use (80% or greater cannabis positive samples). Intermittent cannabis users showed superior retention in naltrexone treatment (median days retained = 133; mean = 112.8, SE = 17.5), compared to abstinent (median = 35; mean = 47.3, SE = 9.2) or consistent users (median = 35; mean = 68.3, SE = 14.1) (log rank = 12.2, df = 2, p = .002). The effect remained significant in a Cox model after adjustment for baseline level of heroin use and during treatment level of cocaine use. Intermittent cannabis use was also associated with greater adherence to naltrexone pill-taking. Treatment interacted with cannabis use level, such that intensive behavioral therapy appeared to moderate the adverse prognosis in the consistent cannabis use group. The association between moderate cannabis use and improved retention on naltrexone treatment was replicated. Experimental studies are needed to directly test the hypothesis that cannabinoid agonists exert a beneficial pharmacological effect on naltrexone maintenance and to understand the mechanism.

Betting on change: modeling transitional probabilities to guide therapy development for opioid dependence.

This study investigated the process of change by modeling transitions among four clinical states encountered in 64 detoxified opiate-dependent individuals treated with daily oral naltrexone: no opiate use, blocked opiate use (i.e., opiate use while adhering to oral naltrexone), unblocked opiate use (i.e., opiate use after having discontinued oral naltrexone), and treatment dropout. The effects of baseline characteristics and two psychosocial interventions of differing intensity, behavioral naltrexone therapy (BNT) and compliance enhancement (CE), on these transitions were studied. Participants using greater quantities of opiates were more likely than other participants to be retained in BNT relative to CE. Markov modeling indicated a transition from abstinence to treatment dropout was approximately 3.56 times greater among participants in CE relative to participants in BNT, indicating the more comprehensive psychosocial intervention kept participants engaged in treatment longer. Transitions to stopping treatment were more likely to occur after unblocked opiate use in both treatments. Continued opiate use while being blocked accounted for a relatively low proportion of transitions to abstinence and may have more deleterious effects later in a treatment episode. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

Cognitive deficits in marijuana users: Effects on motivational enhancement therapy plus cognitive behavioral therapy treatment outcome.

Clinical variables that affect treatment outcome for marijuana-dependent individuals are not yet well understood, including the effects of cognitive functioning. To address this, level of cognitive functioning and treatment outcome were investigated. Twenty marijuana-dependent outpatients were administered a neuropsychological battery at treatment entry. All patients received 12 weekly individual sessions of combined motivational enhancement therapy and cognitive behavioral therapy. The Wilcoxon Exact Test was used to compare cognitive functioning test scores between completers and dropouts, and the Fisher Exact Test was used to compare proportion of negative urines between those with higher and lower scores on the cognitive tests. Marijuana abstinence was unrelated to cognitive functioning. However, dropouts scored significantly lower than completers on measures of abstract reasoning and processing accuracy, providing initial evidence that cognitive functioning plays a role in treatment retention of adult marijuana-dependent patients. If supported by further studies, the findings may help inform the development of interventions tailored for cognitively impaired marijuana-dependent patients.

Management of relapse in naltrexone maintenance for heroin dependence.

UNLABELLED: Opioid dependence is a growing public health problem. Maintenance on the antagonist naltrexone for clinic- or office-based treatment of opioid dependence is plagued by high rates of relapse. This paper identifies critical determinants of lapses to opioid use during naltrexone maintenance. Time retained in treatment was examined as a function of whether lapses to opioid use occurred while adherent to naltrexone (blocked use), or after having missed naltrexone doses (unblocked). METHOD: Participants (N=83) met DSM-IV criteria for opioid dependence and identified a significant other willing to participate in their treatment. Following inpatient detoxification, participants were enrolled in a 26-week outpatient course of therapy and naltrexone maintenance. RESULTS: Patients with unblocked use had a very high rate of dropout (10% retained at 6 months), dropout usually occurring within 2 weeks after unblocked use. Patients with only blocked use had less dropout (33% retained at 6 months). However, episodes of blocked use were often followed by unblocked use and dropout. CONCLUSIONS: During naltrexone maintenance for opioid dependence unblocked opioid use calls for immediate intervention, such as detoxification or switching to the partial agonist buprenorphine. Episodes of blocked use warrant increased clinical attention, such as direct observation of naltrexone ingestion, increased dose, or increased intensity of treatment contact. Maintenance on oral naltrexone is a fragile treatment because it is so easily undermined by episodes of opioid use while non-compliant. New long-acting injectable or implantable formulations of naltrexone may address this limitation and should be investigated for treatment of opioid dependence.

Providing live supervision via teleconferencing improves acquisition of motivational interviewing skills after workshop attendance.

Teleconferencing Supervision is a method for training community-based substance abuse clinicians in Motivational Interviewing (MI). Following a 2-day workshop, 13 clinicians received live supervision via telephone during 5 counseling sessions conducted at their community treatment facilities. Clinicians were assessed for skill level at post-workshop, at post-training, and 3 months later; learning was assessed using the MI Treatment Integrity instrument. All summary scores and therapist behavior frequency counts improved by post-training or by the 3 month follow-up, although some gains were not statistically significant. Teleconferencing Supervision may help facilitate the proficient use of MI community clinicians following workshop instruction.

Cognitive deficits predict low treatment retention in cocaine dependent patients.

Previously, we found that impaired cognition predicted treatment dropout from cognitive behavioral therapy (CBT) in a small sample of cocaine dependent patients. To further address the role of impaired cognition in retention and treatment outcome of cocaine-dependent patients in CBT, we expanded a previous investigation to a larger sample, added depressed cocaine patients, and added an additional cognitive assessment. Fifty-six cocaine dependent patients receiving CBT in outpatient clinical trials were assessed for cognitive performance at treatment entry with the computerized MicroCog (MC) and the Wisconsin Card Sort Test (WCST). Treatment completion was defined as 12 or more weeks. Treatment dropouts had significantly lower MC scores (poorer cognitive functioning) than completers on attention, memory, spatial ability, speed, accuracy, global functioning, and cognitive proficiency, with effect sizes in the moderate to large range. These findings were not affected by depression, demographics (age, gender, race, sex, marital status) or drug use (years of cocaine use or average weekly cocaine expenditure in the prior 30 days). In contrast, patients' performance on the WCST was in the average or near-average range, and WCST scores did not differentiate between completers and dropouts. Consistent with previous research, results suggest that mild cognitive impairments (< or =1 S.D. below the mean) negatively affect retention in outpatient CBT treatment for cocaine dependence. Future studies should examine whether there are specific effects of different executive functioning abilities on treatment outcome. Modified behavioral and pharmacologic interventions should be considered to target mild cognitive impairments to improve substance treatment outcome.

The effect of sertraline and environmental context on treating depression and illicit substance use among methadone maintained opiate dependent patients: a controlled clinical trial.

Psychiatric comorbidity, particularly depressive disorders, is associated with continued substance use and poor social functioning among methadone maintained patients. Evidence suggests similar neurochemical and environmental pathways may link the two disorders and it is reasonable to hypothesize that pharmacological and environmental factors play important roles in the treating comorbid depression and substance use. The present study tested the efficacy of sertraline for treating syndromally defined depressive disorders among non-abstinent methadone maintained opiate dependent patients. The moderating effects of environmental context on treatment outcome were also examined. Ninety-five patients were randomized in a 12-week, double-blind, placebo-controlled trial of sertraline, a serotonin-selective re-uptake inhibitor. There was no main effect of sertraline on either depression or substance use outcomes. However, sertraline demonstrated significant ameliorative effects on depression among patients with a more positive environment or less negative environment. The odds of being abstinent from heroin and cocaine were greater for patients on sertraline in environments with relatively less adversity. The findings support the hypothesis that contextual factors moderate the efficacy of pharmacological treatment for depression among methadone patients. They also suggest future research should examine a pharmacological treatment that is combined with a behavioral intervention targeting the accessibility of reinforcement or reducing the impact of aversive environmental interactions.