Context No randomized trials have examined treatments for prescription opioid dependence, despite its increasing prevalence. Objective To evaluate the efficacy of brief and extended buprenorphine-naloxone treatment, with different counseling intensities, for patients dependent upon prescription opioids. Setting, Participants 653 treatment-seeking outpatients dependent on prescription opioids, at 10 U.S. sites from June 2006-July 2009. Design Multi-site, randomized clinical trial, using a two-phase adaptive treatment research design. Brief treatment (Phase 1) included 2-week buprenorphine-naloxone stabilization, 2-week taper, and 8-week post-medication follow-up. Patients with successful opioid use outcomes exited the study; unsuccessful patients entered Phase 2: extended (12-week) buprenorphine-naloxone treatment, 4-week taper, and 8-week post-medication follow-up. Main outcome measures Pre-defined “successful outcome” in each phase: composite measures indicating minimal or no opioid use, based on urine-confirmed self-reports. Interventions In both phases, patients were randomized to Standard Medical Management (SMM) or SMM+Opioid Drug Counseling (ODC); all received buprenorphine-naloxone. Results During Phase 1, only 6.6% (43/653) of patients had successful outcomes, with no difference between the SMM and SMM+ODC. In contrast, 49.2% (177/360) attained successful outcomes in Phase 2 during extended buprenorphine-naloxone treatment (week 12), with no difference between counseling conditions. Success rates 8 weeks after completing the buprenorphine-naloxone taper (Phase 2, week 24) dropped sharply to 8.6% (31/360), again with no counseling difference. In secondary analyses, successful Phase 2 outcomes were far more common while taking buprenorphine-naloxone than 8 weeks post-taper (49.2% (177/360) vs. 8.6% (31/360), p<0.001). Chronic pain did not affect opioid use outcomes; a history of ever using heroin was associated with lower Phase 2 success rates while taking buprenorphine-naloxone. Conclusions Prescription opioid-dependent patients are most likely to reduce opioid use during buprenorphine-naloxone treatment; if tapered off buprenorphine-naloxone, even after 12 weeks of treatment, the likelihood of unsuccessful outcome is extremely high, even among patients receiving counseling in addition to medical management. Trial Registration ClinicalTrials.gov number NCT00316277

Aim Modafinil was tested for efficacy in facilitating abstinence in cocaine-dependent patients, compared to placebo. Methods This was a double-blind placebo-controlled study, with 12 weeks of treatment and a 4-week follow-up. Six outpatient substance abuse treatment clinics participated in the study. There were 210 treatment-seekers randomized, having a diagnosis of cocaine dependence; 72 participants were randomized to placebo, 69 to modafinil 200 mg, and 69 to modafinil 400 mg, taken once daily on awakening. Participants came to the clinic three times per week for assessments and urine drug screens, and had one hour of individual psychotherapy weekly. The primary outcome measure was the weekly percentage of cocaine non-use days. Results The GEE regression analysis showed that for the total sample, there was no significant difference between either modafinil group and placebo in the change in average weekly percent of cocaine non-use days over the 12-week treatment period (p > 0.79). However, two secondary outcomes showed significant effects by modafinil 200 mg: the maximum number of consecutive non-use days for cocaine (p = 0.02), and a reduction in craving (p = 0.04). Also, a post hoc analysis showed a significant effect of modafinil that increased the weekly percentage of non-use days in the subgroup of those cocaine patients who did not have a history of alcohol dependence (p < 0.02). Conclusions These data suggest that modafinil, in combination with individual behavioral therapy, was effective for increasing cocaine non-use days in participants without co-morbid alcohol dependence, and in reducing cocaine craving.

Pregnant substance users can benefit significantly from substance abuse treatment but treatment retention can be challenging. Two hundred pregnant substance users entering outpatient substance abuse treatment at 1 of 4 treatment programs were randomized to receive either 3 individual sessions of Motivational Enhancement Therapy for pregnant substance users (MET-PS) or the first 3 individual sessions normally provided by the program. All participants were encouraged to participate in all other treatment offered by the program. Outcome measures included treatment utilization according to clinic records, qualitative urine toxicology measures, and self-report of substance use. One hundred and sixty two participants (i.e., 81%) completed the 1 month active phase. Participants attended 62% of scheduled treatment on average and reported decreased substance use during the first month of treatment, with no differences between MET-PS and treatment as usual participants. There was some evidence that the efficacy of MET-PS varied between sites and that MET-PS might be more beneficial than TAU in decreasing substance use in minority participants. These results suggest that MET-PS is not more effective than treatment as usual for pregnant substance users in general but that there might be particular subgroups or treatment programs for which MET-PS might be more or less effective than treatment as usual.

BACKGROUND: The Patient Health Questionnaire depression module (PHQ-9) is a brief (10 items) screening and monitoring measure designed for use in primary care settings that operationalizes most of the DSM-IV and ICD-9 diagnostic criteria for major depression. In the United States, the PHQ-9 has become the recommended depression measure in primary care settings. However, there are no published reports of its use in developing countries and no reports of the feasibility of using the Spanish version of the PHQ-9 to screen for depression. METHOD: During a medical brigade in October 2001, we tested the feasibility of using the Spanish PHQ-9 to screen for major depression in primary care clinics. A team of U.S. and Honduran physicians and medical students assessed 199 mothers of children under 10 years of age as part of a depression prevalence study in 5 rural sites. RESULTS: The PHQ-9 proved easy to administer to this population of poor, rural, young, and mostly illiterate Honduran women who had never participated in research before. Rater training required about 30 minutes of instruction for this group of physicians and medical students, plus occasional questions on the first day of use. Duration of administration of the PHQ-9 by interview ranged from 3 to 15 minutes. No items required major modification for cultural differences. The PHQ-9 identified a rate of 15% for major depression in this sample, and the PHQ-9 results showed a sensitivity of 77% and a specificity of 100% compared with the Structured Clinical Interview for DSM-IV mood disorders module. CONCLUSION: Like the English PHQ-9, the Spanish PHQ-9 is an efficient and reliable screening measure for major depression in primary care. It is useful as a research measure for estimating the prevalence of major depression and as an aid to the primary care clinician in rural Honduras.

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.

Objective High smoking rates in adults with attention deficit hyperactivity disorder (ADHD) and nicotine’s amelioration of ADHD suggest that effective ADHD treatment might facilitate abstinence in smokers with ADHD. The present study evaluated if using osmotic release 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 one month follow-up conducted at six clinical sites between December 2005 and January 2008. Adults (18–55), meeting DSM-IV criteria for ADHD and interested in quitting smoking were randomized to OROS-MPH titrated to 72 mg/day (n=127) or placebo (n=128). All participants received brief weekly individual smoking cessation counseling for 11 weeks and 21 mg/day nicotine patch 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 randomized, 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 (odds ratio, 1.1; 95% confidence interval, 0.63 – 1.79; p=0.81). OROS-MPH, relative to placebo, evidenced a greater reduction in DSM-IV ADHD-RS score (p<0.0001) and in cigarettes per day during the post-quit phase (p=.016). OROS-MPH, relative to placebo, increased blood pressure and heart rate to a statistically, but not clinically, significant degree; medication discontinuation did not differ significantly between treatments. Conclusions ADHD treatment 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.

Aims We evaluated the immunogenicity, efficacy, and safety of succinylnorcocaine conjugated to cholera toxin B protein as a vaccine for cocaine dependence. Methods This 6-site, 24 week Phase III randomized double-blind placebo-controlled trial assessed efficacy during weeks 8 to 16. We measured urine cocaine metabolites thrice weekly as the main outcome. Results The 300 subjects (76% male, 72% African-American, mean age 46 years) had smoked cocaine on average for 13 days monthly at baseline. We hypothesized that retention might be better and positive urines lower for subjects with anti-cocaine IgG levels of ≥ 42 μg/mL (high IgG), which was attained by 67% of the 130 vaccine subjects receiving five vaccinations. Almost 3-times fewer high than low IgG subjects dropped out (7% vs 20%). Although for the full 16 weeks cocaine positive urine rates showed no significant difference between the three groups (placebo, high, low IgG), after week 8, more vaccinated than placebo subjects attained abstinence for at least two weeks of the trial (24% vs 18%), and the high IgG group had the most cocaine-free urines for the last 2 weeks of treatment (OR=3.02), but neither were significant. Injection site reactions of induration and tenderness differed between placebo and active vaccine, and the 29 serious adverse events did not lead to treatment related withdrawals, or deaths. Conclusions The vaccine was safe, but it only partially replicated the efficacy found in the previous study based on retention and attaining abstinence.

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.