Gregory S. Brigham

Do Treatment Improvements in PTSD Severity Affect Substance Use Outcomes? A Secondary Analysis From a Randomized Clinical Trial in NIDA's Clinical Trials Network

OBJECTIVE The purpose of the analysis was to examine the temporal course of improvement in symptoms of posttraumatic stress disorder (PTSD) and substance use disorder among women in outpatient substance abuse treatment. METHOD Participants were 353 women randomly assigned to 12 sessions of either trauma-focused or health education group treatment. PTSD and substance use assessments were conducted during treatment and posttreatment at 1 week and after 3, 6, and 12 months. A continuous Markov model was fit on four defined response categories (nonresponse, substance use response, PTSD response, or global response [improvement in both PTSD and substance use]) to investigate the temporal association between improvement in PTSD and substance use symptom severity during the studys treatment phase. A generalized linear model was applied to test this relationship over the follow-up period. RESULTS Subjects exhibiting nonresponse, substance use response, or global response tended to maintain original classification; subjects exhibiting PTSD response were significantly more likely to transition to global response over time, indicating maintained PTSD improvement was associated with subsequent substance use improvement. Trauma-focused treatment was significantly more effective than health education in achieving substance use improvement, but only among those who were heavy substance users at baseline and had achieved significant PTSD reductions. CONCLUSIONS PTSD severity reductions were more likely to be associated with substance use improvement, with minimal evidence of substance use symptom reduction improving PTSD symptoms. Results support the self-medication model of coping with PTSD symptoms and an empirical basis for integrated interventions for improved substance use outcomes in patients with severe symptoms.

Multisite Randomized Trial of Behavioral Interventions for Women With Co-Occurring PTSD and Substance Use Disorders

The authors compared the effectiveness of the Seeking Safety group, cognitive-behavioral treatment for substance use disorder and posttraumatic stress disorder (PTSD), to an active comparison health education group (Womens Health Education [WHE]) within the National Institute on Drug Abuses Clinical Trials Network. The authors randomized 353 women to receive 12 sessions of Seeking Safety (M = 6.2 sessions) or WHE (M = 6.0 sessions) with follow-up assessment 1 week and 3, 6, and 12 months posttreatment. Primary outcomes were the Clinician Administered PTSD Scale (CAPS), the PTSD Symptom Scale-Self Report (PSS-SR), and a substance use inventory (self-reported abstinence and percentage of days of use over 7 days). Intention-to-treat analysis showed large, clinically significant reductions in CAPS and PSS-SR symptoms (d = 1.94 and 1.12, respectively) but no reliable difference between conditions. Substance use outcomes were not significantly different over time between the two treatments and at follow-up showed no significant change from baseline. Study results do not favor Seeking Safety over WHE as an adjunct to substance use disorder treatment for women with PTSD and reflect considerable opportunity to improve clinical outcomes in community-based treatments for these co-occurring conditions.

Primary outcome indices in illicit drug dependence treatment research: systematic approach to selection and measurement of drug use end-points in clinical trials.

AIMS Clinical trials test the safety and efficacy of behavioral and pharmacological interventions in drug-dependent individuals. However, there is no consensus about the most appropriate outcome(s) to consider in determining treatment efficacy or on the most appropriate methods for assessing selected outcome(s). We summarize the discussion and recommendations of treatment and research experts, convened by the US National Institute on Drug Abuse, to select appropriate primary outcomes for drug dependence treatment clinical trials, and in particular the feasibility of selecting a common outcome to be included in all or most trials. METHODS A brief history of outcomes employed in prior drug dependence treatment research, incorporating perspectives from tobacco and alcohol research, is included. The relative merits and limitations of focusing on drug-taking behavior, as measured by self-report and qualitative or quantitative biological markers, are evaluated. RESULTS Drug-taking behavior, measured ideally by a combination of self-report and biological indicators, is seen as the most appropriate proximal primary outcome in drug dependence treatment clinical trials. CONCLUSIONS We conclude that the most appropriate outcome will vary as a function of salient variables inherent in the clinical trial, such as the type of intervention, its target, treatment goals (e.g. abstinence or reduction of use) and the perspective being taken (e.g. researcher, clinical program, patient, society). It is recommended that a decision process, based on such trial variables, be developed to guide the selection of primary and secondary outcomes as well as the methods to assess them.

Impact of attention-deficit/hyperactivity disorder (ADHD) treatment on smoking cessation intervention in ADHD smokers: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE High smoking rates in adults with attention-deficit/hyperactivity disorder (ADHD) and nicotines amelioration of ADHD suggest that effective ADHD treatment might facilitate abstinence in smokers with ADHD. The present study evaluated if using osmotic-release oral system methylphenidate (OROS-MPH) to treat ADHD enhances response to smoking cessation treatment in smokers with ADHD. METHOD A randomized, double-blind, placebo-controlled, 11-week trial with a 1-month follow-up was conducted at 6 clinical sites between December 2005 and January 2008. Adults (aged 18-55 years) meeting DSM-IV criteria for ADHD and interested in quitting smoking were randomly assigned to OROS-MPH titrated to 72 mg/d (n = 127) or placebo (n = 128). All participants received brief weekly individual smoking cessation counseling for 11 weeks and 21 mg/d nicotine patches starting on the smoking quit day (day 27) through study week 11. Outcome measures included prolonged smoking abstinence and DSM-IV ADHD Rating Scale (ADHD-RS) score. RESULTS Of 255 randomly assigned participants, 204 (80%) completed the trial. Prolonged abstinence rates, 43.3% and 42.2%, for the OROS-MPH and placebo groups, respectively, did not differ significantly (OR = 1.1; 95% CI, 0.63-1.79; P = .81). Relative to placebo, OROS-MPH evidenced a greater reduction in DSM-IV ADHD-RS score (P < .0001) and in cigarettes per day during the post-quit phase (P = .016). Relative to placebo, OROS-MPH increased blood pressure and heart rate to a statistically, but not clinically, significant degree (P < .05); medication discontinuation did not differ significantly between treatments. CONCLUSIONS Treatment for ADHD did not improve smoking cessation success; OROS-MPH, relative to placebo, effectively treated ADHD and was safe and generally well tolerated in this healthy sample of adult ADHD smokers. TRIAL REGISTRATION clinical trials.gov Identifier: NCT00253747.

Partnerships and pathways of dissemination: The National Institute on Drug Abuse—Substance Abuse and Mental Health Services Administration Blending Initiative in the Clinical Trials Network

Since 2001, the National Drug Abuse Treatment Clinical Trials Network (CTN) has worked to put the results of its trials into the hands of community treatment programs, in large part through its participation in the National Institute on Drug Abuse-Substance Abuse and Mental Health Services Administration Blending Initiative and its close involvement with the Center for Substance Abuse Treatments Addiction Technology Transfer Centers. This article describes (a) the CTNs integral role in the Blending Initiative, (b) key partnerships and dissemination pathways through which the results of CTN trials are developed into blending products and then transferred to community treatment programs, and (c) three blending initiatives involving buprenorphine, motivational incentives, and motivational interviewing. The Blending Initiative has resulted in high utilization of its products, preparation of more than 200 regional trainers, widespread training of service providers in most U.S. States, Puerto Rico, and the U.S. Virgin Islands and movement toward the development of Web-based implementation supports and technical assistance. Implications for future directions of the Blending Initiative and opportunities for research are discussed.

From research to the real world: buprenorphine in the decade of the Clinical Trials Network.

The National Institute on Drug Abuse (NIDA) established the National Drug Abuse Treatment Clinical Trials Network (CTN) in 1999 to bring researchers and treatment providers together to develop a clinically relevant research agenda. Initial CTN efforts addressed the use of buprenorphine, a mu-opioid partial agonist, as treatment for opioid dependence. Strong evidence of buprenorphines therapeutic efficacy was demonstrated in clinical trials involving several thousand opioid-dependent participants, and in 2002, the Food and Drug Administration approved buprenorphine for the treatment of opioid dependence. With the advent of a sublingual tablet containing both buprenorphine and naloxone to mitigate abuse and diversion (Suboxone), buprenorphine appeared poised to be the first-line treatment for opioid addiction. Notwithstanding its many attributes, certain implementation barriers remained to be addressed in CTN studies, and these efforts have brought a body of knowledge on buprenorphine to frontline clinicians. The purpose of this article is to review CTN-based buprenorphine research and related efforts to overcome challenges to the implementation of buprenorphine therapy in mainstream practice. Furthermore, this article explores current issues and future challenges that may require additional CTN efforts.

A randomized trial of concurrent smoking-cessation and substance use disorder treatment in stimulant-dependent smokers

OBJECTIVE To evaluate the impact of concurrent treatments for substance use disorder and nicotine-dependence for stimulant-dependent patients. METHOD A randomized, 10-week trial with follow-up at 3 and 6 months after smoking quit date conducted at 12 substance use disorder treatment programs between February 2010 and July 2012. Adults meeting DSM-IV-TR criteria for cocaine and/or methamphetamine dependence and interested in quitting smoking were randomized to treatment as usual (n = 271) or treatment as usual with smoking-cessation treatment (n = 267). All participants received treatment as usual for substance use disorder treatment. Participants assigned to treatment as usual with concurrent smoking-cessation treatment received weekly individual smoking cessation counseling and extended-release bupropion (300 mg/d) during weeks 1-10. During post-quit treatment (weeks 4-10), participants assigned to treatment as usual with smoking-cessation treatment received a nicotine inhaler and contingency management for smoking abstinence. Weekly proportion of stimulant-abstinent participants during the treatment phase, as assessed by urine drug screens and self-report, was the primary outcome. Secondary measures included other substance/nicotine use outcomes and treatment attendance. RESULTS There were no significant treatment effects on stimulant-use outcomes, as measured by the primary outcome and stimulant-free days, on drug-abstinence, or on attendance. Participants assigned to treatment as usual with smoking-cessation treatment, relative to those assigned to treatment as usual, had significantly better outcomes for drug-free days at 6-month follow-up (χ(2)(1) = 4.09, P <.05), with a decrease in drug-free days from baseline of -1.3% in treatment as usual with smoking-cessation treatment and of -7.6% in treatment as usual. Participants receiving treatment as usual with smoking-cessation treatment, relative to those receiving treatment as usual, had significantly better outcomes on smoking point-prevalence abstinence (25.5% vs 2.2%; χ(2)(1) = 44.69, P < .001; OR =18.2). CONCLUSIONS These results suggest that providing smoking-cessation treatment to illicit stimulant-dependent patients in outpatient substance use disorder treatment will not worsen, and may enhance, abstinence from nonnicotine substance use. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01077024.

Stimulant abuser groups to engage in 12-Step: A multisite trial in the National Institute on Drug Abuse Clinical Trials Network

AIMS The study evaluated the effectiveness of an 8-week combined group plus individual 12-step facilitative intervention on stimulant drug use and 12-step meeting attendance and service. DESIGN Multisite randomized controlled trial, with assessments at baseline, mid-treatment, end of treatment, and 3- and 6-month post-randomization follow-ups (FUs). SETTING Intensive outpatient substance treatment programs. PARTICIPANTS Individuals with stimulant use disorders (n = 471) randomly assigned to treatment as usual (TAU) or TAU into which the Stimulant Abuser Groups to Engage in 12-Step (STAGE-12) intervention was integrated. MEASUREMENTS Urinalysis and self-reports of substance use and 12-step attendance and activities. INTERVENTION Group sessions focused on increasing acceptance of 12-step principles; individual sessions incorporated an intensive referral procedure connecting participants to 12-step volunteers. FINDINGS Compared with TAU, STAGE-12 participants had significantly greater odds of self-reported stimulant abstinence during the active 8-week treatment phase; however, among those who had not achieved abstinence during this period, STAGE-12 participants had more days of use. STAGE-12 participants had lower Addiction Severity Index Drug Composite scores at and a significant reduction from baseline to the 3-month FU, attended 12-step meetings on a greater number of days during the early phase of active treatment, engaged in more other types of 12-step activities throughout the active treatment phase and the entire FU period, and had more days of self-reported service at meetings from mid-treatment through the 6-month FU. CONCLUSIONS The present findings are mixed with respect to the impact of integrating the STAGE-12 intervention into intensive outpatient drug treatment compared with TAU on stimulant drug use. However, the results more clearly indicate that individuals in STAGE-12 had higher rates of 12-step meeting attendance and were engaged in more related activities throughout both the active treatment phase and the entire 6-month FU period than did those in TAU.

Multisite, randomized, double-blind, placebo-controlled pilot clinical trial to evaluate the efficacy of buspirone as a relapse-prevention treatment for cocaine dependence.

OBJECTIVE To evaluate the potential efficacy of buspirone as a relapse-prevention treatment for cocaine dependence. METHOD A randomized, double-blind, placebo-controlled, 16-week pilot trial was conducted at 6 clinical sites between August 2012 and June 2013. Adult crack cocaine users meeting DSM-IV-TR criteria for current cocaine dependence who were scheduled to be in inpatient/residential substance use disorder (SUD) treatment for 12-19 days when randomized and planning to enroll in local outpatient treatment through the end of the active treatment phase were randomized to buspirone titrated to 60 mg/d (n = 35) or placebo (n = 27). All participants received psychosocial treatment as usually provided by the SUD treatment programs in which they were enrolled. Outcome measures included maximum days of continuous cocaine abstinence (primary), proportion of cocaine use days, and days to first cocaine use during the outpatient treatment phase (study weeks 4-15) as assessed by self-report and urine drug screens. RESULTS There were no significant treatment effects on maximum continuous days of cocaine abstinence or days to first cocaine use. In the female participants (n = 23), there was a significant treatment-by-time interaction effect (χ²₁ = 15.26, P < .0001), reflecting an increase in cocaine use by those receiving buspirone, relative to placebo, early in the outpatient treatment phase. A similar effect was not detected in the male participants (n = 39; χ²₁ = 0.14, P = .70). CONCLUSIONS The results suggest that buspirone is unlikely to have a beneficial effect on preventing relapse to cocaine use and that buspirone for cocaine-dependent women may worsen their cocaine use outcomes. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT01641159.

Impulsivity is associated with treatment non-completion in cocaine- and methamphetamine-dependent patients but differs in nature as a function of stimulant-dependence diagnosis.

Greater impulsivity, assessed by the Barratt Impulsiveness Scale-11 (BIS-11) and Stroop interference scores, has been associated with treatment completion in cocaine-dependent patients. This study evaluated the relationships among impulsivity, stimulant-dependence diagnosis, and treatment completion. Six sites evaluating 12-step facilitation for stimulant abusers obtained the BIS-11 and Stroop from 182 methamphetamine- and/or cocaine-dependent participants. Methamphetamine-dependent, relative to cocaine-dependent, participants evidenced significantly greater BIS-11 non-planning and total scores. There was a trend for poorer response inhibition, measured by the Stroop, in cocaine-dependent, relative to methamphetamine-dependent, participants. Accounting for other factors related to treatment completion, BIS-11 motor score, assessing the tendency to act without thinking, predicted treatment completion for both cocaine-dependent and methamphetamine-dependent patients. These results suggest that methamphetamine-dependent and cocaine-dependent patients may have different impulsivity profiles but that the BIS-11 may be useful in identifying both methamphetamine-dependent and cocaine-dependent patients who are at risk for treatment non-completion.