Faculty Bibliography

AIMS/OBJECTIVE:To describe drug use and safety with intramuscular injectable extended-release naltrexone (XR-NTX) in opioid dependence during a 1-year open-label extension phase. DESIGN/METHODS:Following 6 months of randomized, double-blind, placebo (PBO)-controlled injections given every 28 days, patients receiving XR-NTX 380 mg continued and PBO patients were switched to open-label XR-NTX, with monthly individual drug counseling, for a further year. SETTING/METHODS:Thirteen clinical sites in Russia. PARTICIPANTS/METHODS:Adult opioid-dependent outpatients. MEASUREMENTS/METHODS:Monthly urine samples; reports of craving and functioning; adverse events. FINDINGS/RESULTS:For the open-label extension (n = 114), 67 continued on XR-NTX and 47 switched from PBO during the double-blind phase to XR-NTX during the open-label phase. Overall, 62.3% (95% CI: 52.7%, 71.2%) completed the extension. Discontinuation occurred most commonly because of withdrawal of consent (18.4%) and loss to follow-up (11.4%); two patients discontinued as a result of lack of efficacy and one because of adverse events. Urine testing revealed that 50.9% (41.5%, 60.4%) were abstinent from opioids at all assessments during the 1-year open-label phase. Adverse events reported by 21.1% of patients were judged to be study drug-related. Injection site reactions were infrequent (6.1%) and the majority were mild. Elevations in liver function tests occurred for 16.7% of patients, but none of these elevations was judged to be clinically significant. No patients died, overdosed or discontinued as a result of severe adverse events. CONCLUSIONS:During a 1-year open-label extension phase of injectable XR-NTX for the prevention of relapse in opioid dependence, 62.3% of patients completed the phase and 50.9% were abstinent from opioids. No new safety concerns were evident.

OBJECTIVE:Evidence suggests that substance abuse is becoming more prevalent in middle-aged adults. The objective of this secondary analysis was to add to the growing empirical literature on the unique features of middle-aged substance abuse populations. METHODS:We descriptively compared baseline demographic and clinical characteristics of middle-aged (age 45-62 years, n = 111) and younger (age 18-44 years, n = 395) substance abusers entering a Web-based psychosocial treatment study as part of the National Institute on Drug Abuse Clinical Trials Network. RESULTS:A significantly greater percentage of middle-aged adults were nonwhite and had a marital status other than single/never married. There was a significant association between frequency of Internet use and the age group. Forty-six percent of middle-aged adults versus 21% of younger adults reported no Internet use in the prior 90 days. A significantly greater percentage of middle-aged adults used cocaine, and a significantly greater percentage of younger adults used marijuana and opioids. Clinically significant cognitive impairment (z < -1.0) was found for the average participant in both groups on logical association of familiar concepts. CONCLUSIONS:This secondary analysis of a National Institute on Drug Abuse Clinical Trials Network study provides additional information on the unique features of middle-aged substance abusers. Increasing knowledge of similarities and differences between younger and middle-aged substance abusers can help with potential age-specific substance abuse treatment planning.

AIM/OBJECTIVE:To evaluate whether venlafaxine-extended release (VEN-XR) is an effective treatment for cannabis dependence with concurrent depressive disorders. DESIGN/METHODS:This was a randomized, 12-week, double-blind, placebo-controlled trial of out-patients (n = 103) with DSM-IV cannabis dependence and major depressive disorder or dysthymia. Participants received up to 375 mg VEN-XR on a fixed-flexible schedule or placebo. All patients received weekly individual cognitive-behavioral psychotherapy that primarily targeted marijuana use. SETTINGS/METHODS:The trial was conducted at two university research centers in the United States. PARTICIPANTS/METHODS:One hundred and three cannabis-dependent adults participated in the trial. MEASUREMENTS/METHODS:The primary outcome measures were (i) abstinence from marijuana defined as at least two consecutive urine-confirmed abstinent weeks and (ii) improvement in depressive symptoms based on the Hamilton Depression Rating Scale. FINDINGS/RESULTS:The proportion of patients achieving a clinically significant mood improvement (50% decrease in Hamilton Depression score from baseline) was high and did not differ between groups receiving VEN-XR (63%) and placebo (69%) (χ1 (2)  = 0.48, P = 0.49). The proportion of patients achieving abstinence was low overall, but was significantly worse on VEN-XR (11.8%) compared to placebo (36.5%) (χ1 (2)  = 7.46, P < 0.01; odds ratio = 4.51, 95% confidence interval: 1.53, 13.3). Mood improvement was associated with reduction in marijuana use in the placebo group (F1,179  = 30.49, P < 0.01), but not the VEN-XR group (F1,186  = 0.02, P = 0.89). CONCLUSIONS:For depressed, cannabis-dependent patients, venlafaxine-extended release does not appear to be effective at reducing depression and may lead to an increase in cannabis use.

AIMS/OBJECTIVE:Little is known about the differential effects of independent and substance-induced major depression on the longitudinal course of alcohol, cocaine and heroin disorders when studied prospectively. DESIGN/METHODS:Consecutively admitted in-patients, evaluated at baseline, 6-, 12- and 18-month follow-ups. SETTING/METHODS:Baseline evaluations in a short-stay in-patient urban community psychiatric hospital unit. PARTICIPANTS/METHODS:Adults (n = 250) with current DSM-IV cocaine, heroin and/or alcohol dependence at baseline. MEASUREMENTS/METHODS:The Psychiatric Research Interview for Substance and Mental Disorders (PRISM), used to evaluate independent and substance-induced major depression, alcohol, cocaine and heroin dependence, and other psychiatric disorders. Outcomes for each substance: (i) time (weeks) from hospital discharge to first use; (ii) time from discharge to onset of sustained (≥26 weeks) remission from dependence; (iii) time from onset of sustained remission to relapse. FINDINGS/RESULTS:Substance-induced major depression significantly predicted post-discharge use of alcohol, cocaine and heroin (hazard ratios 4.7, 5.3 and 6.5, respectively). Among patients achieving stable remissions from dependence, independent major depression predicted relapse to alcohol and cocaine dependence (hazard ratios 2.3 and 2.7, respectively). CONCLUSIONS:Substance-induced and independent major depressions were both related to post-discharge use of alcohol, cocaine and heroin. The findings suggest the importance of clinical attention to both types of depression in substance abusing patients.

BACKGROUND: During the past decade, several novel medication treatments and psychosocial interventions have been tested. Overall, their impact on reducing alcohol use and preventing relapse has been modest. These outcomes have spurred researchers to investigate whether the addition of manualized psychosocial therapies with demonstrated efficacy to pharmacotherpy would have a synergistic effect. OBJECTIVES/OBJECTIVE: We conducted a meta-analysis to test the hypothesis that the addition of manualized psychosocial therapies would reduce the frequency of relapse. RESULTS: This review analyzed data from six studies. Among studies that used random assignment to manually guided psychosocial interventions, the rates of relapse between the naltrexone plus a psychosocial intervention and naltrexone without a psychosocial intervention were very similar. Among patients allocated to placebo, similar rates of relapse were also found between Cognitive Behavioral Therapy (CBT) and non-CBT. In studies which used manualized psychotherapies as a platform, relapse rates were similar between naltrexone and placebo. In contrast, studies using Treatment As Usual psychotherapy as a platform demonstrated lower rates of relapse in the naltrexone group, compared to placebo group. CONCLUSIONS: We conclude that CBT does not appear to offer benefits beyond those derived from study medications. SCIENTIFIC SIGNIFICANCE/CONCLUSIONS: The benefit of the addition of CBT to medication in preventing relapse may be limited.

UNLABELLED:We aimed to assess the efficacy and safety of an injectable, once monthly extended-release formulation of the opioid antagonist naltrexone (XR-NTX) for treatment of patients with opioid dependence after detoxification. Two hundreds and fifty patients with opioid dependence were enrolled into the double-blind, placebo-controlled, randomized, 24-week trial. Patients aged 18 years or over who had inpatient detoxification and 7 days or more off all opioids were enrolled at 13 clinical sites in Russia. We randomly assigned patients (1:1) to either 380 mg XR-NTX (n=124) or placebo (n=126). Participants also received 12 biweekly counseling sessions. The primary endpoint was the response profile for confirmed abstinence during weeks 5-24 assessed by urine drug tests and self report of non-use. Secondary endpoints were self-reported opioid- free days, opioid craving scores, number of days of retention, and relapse to physiological opioid dependence. IN CONCLUSION/CONCLUSIONS:XR-NTX represents a new treatment option. XR-NTX in conjunction with psychosocial treatment was more effective for treatment of opioid dependence compare to psychosocial support and placebo.

BACKGROUND:Cocaine dependence is a substantial public health problem, yet there are no clearly effective medication treatments. Amphetamine and topiramate have both shown promise for the treatment of cocaine dependence in preclinical and early-stage clinical studies. METHODS:Eighty-one cocaine-dependent adults were randomized to receive a combination of extended-release mixed amphetamine salts (MAS-ER) and topiramate or placebo for 12 weeks under double-blind conditions. MAS-ER doses were titrated over 2 weeks to a maximum dose of 60 mg daily, and topiramate doses were titrated over 6 weeks to a maximum dose of 150 mg twice daily. All participants received a supportive behavioral intervention. The primary outcome was the proportion of individuals who achieved 3 consecutive weeks of abstinence as measured by urine toxicology confirmed self-report. RESULTS:The overall proportion of participants who achieved 3 consecutive weeks of abstinence was larger in the extended-release mixed amphetamine salts and topiramate group (33.3%) than in placebo group (16.7%). There was a significant moderating effect of baseline total number of cocaine use days (Wald χ(2) = 3.75, df = 1, p = .05) on outcome, suggesting that the combination treatment was most effective for participants with a high baseline frequency of cocaine use. CONCLUSIONS:The results of this study supported our hypothesis that the combination of MAS-ER and topiramate would be superior to placebo in achieving 3 weeks of consecutive abstinence. These findings provide evidence that the combination of MAS-ER and topiramate is efficacious in promoting abstinence in cocaine-dependent individuals.

The purpose of this multisite clinical trial was to evaluate the effectiveness of a web-based version of the Community Reinforcement Approach, plus motivational incentives, within community-based, outpatient substance abuse treatment. This ongoing study is being conducted within the National Drug Abuse Treatment Clinical Trials Network, funded by the National Institute on Drug Abuse. Midway through the enrollment of 500 participants, the study is being implemented in 10 treatment programs across the United States. Information is provided on design, sample, intervention and technology, and preliminary lessons learned.

Gender-based relationship power is frequently linked to women's capacity to reduce sexual risk behaviors. This study offers an exploration of predictors of relationship power, as measured by the multidimensional and theoretically grounded sexual relationship power scale, among women in outpatient substance abuse treatment. Linear models were used to test nine predictors (age, race/ethnicity, education, time in treatment, economic dependence, substance use, sexual concurrency, partner abuse, and sex role orientation) of relationship power among 513 women participating in a multi-site HIV risk reduction intervention study. Significant predictors of relationship control included having a non-abusive male partner, only one male partner, and endorsing traditional masculine (or both masculine and feminine) sex role attributes. Predictors of decision-making dominance were interrelated, with substance use × partner abuse and age × sex role orientation interactions. Results contribute to the understanding of factors which may influence relationship power and to their potential role in HIV sexual risk reduction interventions.

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/METHODS: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.