Albert Hasson

Buprenorphine tapering schedule and illicit opioid use

AIMS To compare the effects of a short or long taper schedule after buprenorphine stabilization on participant outcomes as measured by opioid-free urine tests at the end of each taper period. DESIGN This multi-site study sponsored by Clinical Trials Network (CTN, a branch of the US National Institute on Drug Abuse) was conducted from 2003 to 2005 to compare two taper conditions (7 days and 28 days). Data were collected at weekly clinic visits to the end of the taper periods, and at 1-month and 3-month post-taper follow-up visits. SETTING Eleven out-patient treatment programs in 10 US cities. INTERVENTION Non-blinded dosing with Suboxone during the 1-month stabilization phase included 3 weeks of flexible dosing as determined appropriate by the study physicians. A fixed dose was required for the final week before beginning the taper phase. MEASUREMENTS The percentage of participants in each taper group providing urine samples free of illicit opioids at the end of the taper and at follow-up. FINDINGS At the end of the taper, 44% of the 7-day taper group (n = 255) provided opioid-free urine specimens compared to 30% of the 28-day taper group (n = 261; P = 0.0007). There were no differences at the 1-month and 3-month follow-ups (7-day = 18% and 12%; 28-day = 18% and 13%, 1 month and 3 months, respectively). CONCLUSION For individuals terminating buprenorphine pharmacotherapy for opioid dependence, there appears to be no advantage in prolonging the duration of taper.

A multi-site, two-phase, Prescription Opioid Addiction Treatment Study (POATS): rationale, design, and methodology.

The National Institute on Drug Abuse Clinical Trials Network launched the Prescription Opioid Addiction Treatment Study (POATS) in response to rising rates of prescription opioid dependence and gaps in understanding the optimal course of treatment for this population. POATS employed a multi-site, two-phase adaptive, sequential treatment design to approximate clinical practice. The study took place at 10 community treatment programs around the United States. Participants included men and women age > or =18 who met Diagnostic and Statistical Manual, 4th Edition criteria for dependence upon prescription opioids, with physiologic features; those with a prominent history of heroin use (according to pre-specified criteria) were excluded. All participants received buprenorphine/naloxone (bup/nx). Phase 1 consisted of 4 weeks of bup/nx treatment, including a 14-day dose taper, with 8 weeks of follow-up. Phase 1 participants were monitored for treatment response during these 12 weeks. Those who relapsed to opioid use, as defined by pre-specified criteria, were invited to enter Phase 2; Phase 2 consisted of 12 weeks of bup/nx stabilization treatment, followed by a 4-week taper and 8 weeks of post-treatment follow-up. Participants were randomized at the beginning of Phase 1 to receive bup/nx, paired with either Standard Medical Management (SMM) or Enhanced Medical Management (EMM; defined as SMM plus individual drug counseling). Eligible participants entering Phase 2 were re-randomized to either EMM or SMM. POATS was developed to determine what benefit, if any, EMM offers over SMM in short-term and longer-term treatment paradigm. This paper describes the rationale and design of the study.

Telephone Enhancement of Long-term Engagement (TELE) in Continuing Care for Substance Abuse Treatment: A NIDA Clinical Trials Network (CTN) study

The TELE study examined the feasibility and potential efficacy of phone calls to patients after discharge from short- term inpatient and residential substance abuse treatment programs to encourage compliance with continuing care plans. After review of their continuing care plans, 339 patients from four programs were randomized either to receive calls or to have no planned contact. Ninety-two percent of patients randomized to receive calls received at least one call. No difference was found between groups in self-reported attendance at one or more outpatient counseling sessions after discharge (p = .89). When program records of all participants were examined, those receiving calls had a greater likelihood of documented attendance (48%) than those not called (37%). Results were not statistically significant (p < .003) because of the Hochberg correction for multiple tests. While the phone calls were feasible, the lack of clear evidence of efficacy of the calls suggests the need for further investigation of the role of telephone intervention to encourage compliance and improve outcomes.

Addiction Pharmacotherapy 2000: New Options, New Challenges

Abstract There are many indicators that substance abuse research and treatment are going to become better integrated. Hopefully, this development will produce new treatment options and will improve access and effectiveness of care. Among the most significant factors in this period of change are the advances in addiction pharmacotherapy. For the treatment of alcoholism, disulfiram has been joined by naltrexone. and soon acamprosate will be added to the list of available pharmacotherapies. Individuals with opiate dependence who, for 25 years. were limited to a single medication (methadone) now have LAAM as an available treatment. Furthermore, there is eager anticipation that buprenorphine/naloxone will bring many more opiate users into treatment since it appears that this medication will be available to doctors outside the traditional narcotics treatment program settings. Other opiate addiction treatment options, including sustained-release naltrexone and lofexidine, are in active development. The greatest area of challenge for pharmacotherapy research is the search for stimulant addiction medications. NIDA has extensive efforts underway to discover/develop medicines that can help in the treatment of cocaine and methamphetamine users. During the next decade, those who embrace these new treatments and integrate them into standard care will offer their patients the best chance for recovery.

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.

Cocaine Abuse Among Methadone Maintenance Patients: Are There Effective Treatment Strategies?

Cocaine abuse among patients in methadone maintenance treatment has substantially increased in the past decade. No standard treatment approaches exist to address this problem. Empirical evidence has been collected on the effectiveness of several categories of techniques for treating this problem, including pharmacotherapies, behavioral methods (contingency management and relapse prevention), and methadone dose adjustment. Data on the effectiveness of these techniques is summarized. In addition, other treatment interventions that may be efficacious for this population, including day treatment and sober-living facilities, are described. Finally, methadone clinic management procedures that may aid in the reduction of cocaine abuse by methadone patients are discussed. Although many of these efforts are in early stages of evaluation, there are some reasons for optimism in the development of treatment for these patients.

A Comparison of Buprenorphine Taper Outcomes Between Prescription Opioid and Heroin Users

Objectives: Dependence on prescription opioids (PO) is a growing problem. Although most research with buprenorphine has focused on heroin-dependent populations, we hypothesize that individuals dependent on PO display characteristics that may predict different outcomes in treatment, particularly in short-term taper procedures in which comorbidities such as pain conditions may complicate taper. Methods: This secondary data analysis examined differences in outcomes between PO users (n = 90) and heroin users (n = 426) after a buprenorphine taper. Data were collected in a multisite randomized clinical trial conducted by the National Drug Abuse Treatment Clinical Trials Network at 11 study sites across the United States. After a 4-week buprenorphine induction/stabilization phase, 516 opioid-dependent individuals were randomized into 1 of 2 taper lengths (7 vs 28 days) to assess the association between taper length and outcome. The primary outcome was measured by urine drug test for opioids at the end of the taper period. Craving, withdrawal, and buprenorphine dose were also examined. Results: After controlling for baseline demographic and drug use differences between the opioid use groups, results indicate that a higher percentage of the PO group (49%) provided an opioid-free urine drug specimen at the end of taper compared with the heroin group (36%; &khgr;21 = 6.592, P < 0.010). Conclusion Short-term taper is not recommended as a stand-alone treatment; however, patients may taper from buprenorphine as part of a treatment plan. Despite greater comorbidity, PO users seem to have favorable taper outcomes compared with heroin users. Further studies are required to examine longer-term treatment outcomes.

Reasons for discharge from methadone maintenance for addicts at high risk of HIV infection or transmission.

This article reports on a methadone maintenance program that had the goal of retaining in treatment heroin addicts at high risk of HIV infection and/or transmission. Subjects were recruited from four-high-risk target groups and randomly assigned to either an enhanced or standard methadone maintenance group. The analysis examined predictors of any type of discharge, negative discharge, and circumstantial discharge. Discharge for any reason was more likely for younger individuals, sex industry workers, and high-risk sex partners. Legal supervision at intake and coercion into treatment reduced the probability of discharge for any reason. HIV-positive individuals were more likely to discharge for circumstantial reasons than negative reasons. The probability of circumstantial discharge was increased for males, individuals reporting suicidal ideation, and those scoring higher on an impulse expression scale. The likelihood of circumstantial discharge was decreased for individuals who reported more sources of legal income or who lived someone using illegal drugs. Participation in the enhanced treatment group appeared to reduce the probability of negative, compared with circumstantial, discharge. The findings should assist methadone treatment providers in targeting individuals at high probability of discharge for special efforts to increase treatment retention and to reengage them back into treatment after discharge, as part of a harm-reduction strategy to minimize risks of HIV infection and/or transmission.

Cocaine Use Reduction with Buprenorphine (CURB): Rationale, design, and methodology

BACKGROUND Effective medications to treat cocaine dependence have not been identified. Recent pharmacotherapy trials demonstrate the potential efficacy of buprenorphine (BUP) (alone or with naltrexone) for reducing cocaine use. The National Institute on Drug Abuse Clinical Trials Network (CTN) launched the Cocaine Use Reduction with Buprenorphine (CURB) investigation to examine the safety and efficacy of sublingual BUP (as Suboxone®) in the presence of extended-release injectable naltrexone (XR-NTX, as Vivitrol®) for the treatment of cocaine dependence. This paper describes the design and rationale for this study. METHODS This multi-site, double-blind, placebo-controlled study will randomize 300 participants across 11 sites. Participants must meet the DSM-IV criteria for cocaine dependence and past or current opioid dependence or abuse. Participants are inducted onto XR-NTX after self-reporting at least 7 days of abstinence from opioids and tolerating a naloxone challenge followed by oral naltrexone and are then randomly assigned to one of three medication conditions (4 mg BUP, 16 mg BUP, or placebo) for 8 weeks. Participants receive a second injection of XR-NTX 4 weeks after the initial injection, and follow-up visits are scheduled at 1 and 3 months post-treatment. Participants receive weekly cognitive behavioral therapy (CBT). Recruitment commenced in September, 2011. Enrollment, active medication, and follow-up phases are ongoing, and recruitment is exceeding targeted enrollment rates. CONCLUSIONS This research using 2 medications will demonstrate whether BUP, administered in the presence of XR-NTX, reduces cocaine use in adults with cocaine dependence and opioid use disorders and will demonstrate if XR-NTX prevents development of physiologic dependence on BUP.

A randomized placebo-controlled trial of N-acetylcysteine for cannabis use disorder in adults

BACKGROUND Cannabis use disorder (CUD) is a prevalent and impairing condition, and established psychosocial treatments convey limited efficacy. In light of recent findings supporting the efficacy of N-acetylcysteine (NAC) for CUD in adolescents, the objective of this trial was to evaluate its efficacy in adults. METHODS In a 12-week double-blind randomized placebo-controlled trial, treatment-seeking adults ages 18-50 with CUD (N=302), enrolled across six National Drug Abuse Treatment Clinical Trials Network-affiliated clinical sites, were randomized in a 1:1 ratio to a 12-week course of NAC 1200mg (n=153) or placebo (n=149) twice daily. All participants received contingency management (CM) and medical management. The primary efficacy measure was the odds of negative urine cannabinoid tests during treatment, compared between NAC and placebo participants. RESULTS There was not statistically significant evidence that the NAC and placebo groups differed in cannabis abstinence (odds ratio=1.00, 95% confidence interval 0.63-1.59, p=0.984). Overall, 22.3% of urine cannabinoid tests in the NAC group were negative, compared with 22.4% in the placebo group. Many participants were medication non-adherent; exploratory analysis within medication-adherent subgroups revealed no significant differential abstinence outcomes by treatment group. CONCLUSIONS In contrast with prior findings in adolescents, there is no evidence that NAC 1200mg twice daily plus CM is differentially efficacious for CUD in adults when compared to placebo plus CM. This discrepant finding between adolescents and adults with CUD may have been influenced by differences in development, cannabis use profiles, responses to embedded behavioral treatment, medication adherence, and other factors.