Faculty Bibliography

Limited access to positive reinforcers is a central feature in behavioral formulations of substance use and depression, and evidence suggests both disorders share similar environmental contexts. The Behavioral Therapy for Depression in Drug Dependence (BTDD) was developed to target the density of potential reinforcers in a patient's environment to reduce both depression and illicit substance use using therapeutic techniques from three operant based treatment programs, Community Reinforcement Approach, Changing Reinforcement Events, and Treatment-plan Contingency Management. Results of an uncontrolled Stage Ia trial (n = 29), indicated 48% of the participants demonstrated at least a 50% reduction in baseline depression scores during the 16-session treatment program. Those designated as treatment responders completed more out-of-session behavioral activities, attended more treatment sessions, and demonstrated less benzodiazepine use during the program than non-responders. There were no changes in opiate and cocaine use. BTDD may be a useful adjunct to methadone maintenance for treating comorbid depressive disorders.

Cannabis is the most widely used illicit substance in the United States with especially high prevalence of use among those with psychiatric disorders. Few studies have examined the relationship between concurrent cannabis use and treatment outcome among patients receiving treatment for comorbid substance abuse and psychiatric disorders. This study investigated the effects of cannabis use on treatment retention and abstinence from cocaine among cocaine dependent patients with Attention Deficit Hyperactivity Disorder (ADHD). Cocaine dependent patients diagnosed with current ADHD (DSM-IV, N = 92) aged 25 to 51 participated in a randomized clinical trial of methylphenidate for treatment of ADHD and cocaine dependence in an outpatient setting. The majority of patients (69%) used cannabis during treatment. Results suggest that moderate/intermittent cannabis users had greater retention rates compared to abstainers and consistent users (p = .02). This study is the first to examine concurrent cannabis use in cocaine dependent patients diagnosed with ADHD.

The effectiveness of antagonist maintenance with oral naltrexone for opioid dependence has been limited by high dropout rates. Behavioral Naltrexone Therapy (BNT) was developed to improve retention on oral naltrexone by integrating voucher incentives, Motivational and Cognitive Behavioral therapies, and a significant other for monitoring medication adherence. In a 6-month, randomized, controlled trial in heroin dependent patients, BNT (N = 36) improved retention in treatment compared to a standard treatment control (Compliance Enhancement (CE); N = 33) (log rank = 4.28; p = .04). Most patients retained beyond 3 months achieved abstinence from opioids, but retention at 6 months was only 22% on BNT and 9% on CE. A systematic review of related controlled trials revealed similar effect sizes in the small to medium range, and substantial dropout. There may be a limit on the extent to which behavioral therapy can overcome poor adherence to oral naltrexone. Future research should consider combinations of behavioral methods with new long-acting injectable or implantable naltrexone formulations.

We examined whether drug use behaviors during a 2-week lead-in for a pharmacotherapy trial were predictive of retention in treatment and of the level of cocaine use during the subsequent 12 weeks of treatment. Fifty cocaine dependent patients were grouped based on: (1) principal route of cocaine administration: intranasal versus smoking, and (2) level of cocaine use during the 2-week lead-in: high versus low. Results indicate that level of cocaine use during the 2-week lead-in was a significant predictor of cocaine use during the subsequent 12 weeks of treatment. Patients with reported higher level of use during the lead-in period were more likely to continue using cocaine during the treatment. Patients who used smoking as their primary route of cocaine use were more likely to drop out early in the treatment. Findings of this study suggest that route and level of cocaine use during lead-in be used as a covariate in models testing treatment effect.

OBJECTIVE:Research on the effects of cannabis on the brain and behavior has been surprisingly scarce. In humans, laboratory studies document toxicity and psychoactive effects of cannabinoids. However, among substance abuse patients, only a few studies have prospectively examined the relationship of cannabis use to remission or relapse of use of other substances. Because cannabis is a widely used substance, the authors examined whether cannabis use during follow-up after discharge from inpatient treatment affected cocaine, alcohol, and/or heroin use. METHOD/METHODS:Two hundred fifty patients 18 years old or older from an inpatient psychiatric/substance abuse setting participated in a Psychiatric Research Interview for Substance and Mental Disorders. All patients were diagnosed according to DSM-IV as having current alcohol, cocaine, and/or heroin dependence. Sustained remission was defined as at least 26 weeks without use following hospital discharge. Data were analyzed with Cox proportional hazards models. RESULTS:About one-third of the patients (N=73) used cannabis after hospital discharge. Postdischarge cannabis use substantially and significantly increased the hazard of first use of any substance and strongly reduced the likelihood of stable remission from use of any substance. Examination of specific substances indicated that cannabis use affected first use of alcohol, stable remission, and subsequent relapse of alcohol use as well as first use of cocaine and stable remission but was unrelated to heroin outcomes. CONCLUSIONS:Potential negative clinical implications of cannabis use should be considered when treating dependence on other substances and planning aftercare. Clinical and laboratory research is needed to provide understanding of the mechanisms of cannabinoids in relapse to alcohol and cocaine use.

CONTEXT/BACKGROUND:Depression and substance abuse are common and costly disorders that frequently co-occur, but controversy about effective treatment for patients with both disorders persists. OBJECTIVE:To conduct a systematic review and meta-analysis to quantify the efficacy of antidepressant medications for treatment of combined depression and substance use disorders. DATA SOURCES/METHODS:PubMed, MEDLINE, and Cochrane database search (1970-2003), using the keywords antidepressant treatment or treatment depressed in conjunction with each of the following alcohol dependence, benzodiazepine dependence, opiate dependence, cocaine dependence, marijuana dependence, and methadone; a search of bibliographies; and consultation with experts in the field. STUDY SELECTION/METHODS:Among inclusion criteria used for study selection were prospective, parallel group, double-blind, controlled clinical trials with random assignment to an antidepressant medication or placebo for which trial patients met standard diagnostic criteria for current alcohol or other drug use and a current unipolar depressive disorder. Of the more than 300 citations extracted, 44 were placebo-controlled clinical trials, 14 of which were selected for this analysis and included 848 patients: 5 studies of tricyclic antidepressants, 7 of selective serotonin re-uptake inhibitors, and 2 from other classes DATA EXTRACTION/METHODS:We independently screened the titles and abstracts of each citation, identified placebo-controlled trials of patients with both substance dependence and depression, applied the inclusion criteria, and reached consensus. Data on study methods, sample characteristics, and depression and substance use outcomes were extracted. The principal measure of effect size was the standardized difference between means on the Hamilton Depression Scale (HDS). DATA SYNTHESIS/RESULTS:For the HDS score, the pooled effect size from the random-effects model was 0.38 (95% confidence interval, 0.18-0.58). Heterogeneity of effect on HDS across studies was significant (P <.02), and studies with low placebo response showed larger effects. Moderator analysis suggested that diagnostic methods and concurrent psychosocial interventions influenced outcome. Studies with larger depression effect sizes (>0.5) demonstrated favorable effects of medication on measures of quantity of substance use, but rates of sustained abstinence were low. CONCLUSIONS:Antidepressant medication exerts a modest beneficial effect for patients with combined depressive- and substance-use disorders. It is not a stand-alone treatment, and concurrent therapy directly targeting the addiction is also indicated. More research is needed to understand variations in the strength of the effect, but the data suggest that care be exercised in the diagnosis of depression-either by observing depression to persist during at least a brief period of abstinence or through efforts by clinical history to screen out substance-related depressive symptoms.

There is a noticeable lack of targeted treatment options for marijuana dependence, in particular pharmacologic approaches. This is the first study evaluating a targeted pharmacologic approach for marijuana dependence. The goals of the study were to determine if such patients would seek pharmacologic treatment, whether these patients could be retained in treatment using a design previously developed for cocaine-dependent patients, and especially whether divalproex sodium showed promise as a treatment agent for marijuana dependence. We found that marijuana-dependent patients will seek treatment, and such patients can be adequately maintained in a pharmacologic trial. Regardless of treatment group, patients reported a significant reduction in their frequency and amount of marijuana use as well as a reduction in irritability. Given the lack of proven effective treatments for marijuana dependence, pharmacotherapies should be sought. The design of a preliminary clinical trial should include a psychosocial/behavioral intervention emphasizing motivation and medication compliance and a placebo control group.

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.