Buprenorphine implants for treatment of opioid dependence: randomized comparison to placebo and sublingual buprenorphine/naloxone.

AIMS: To evaluate the safety and efficacy of buprenorphine implants (BI) versus placebo implants (PI) for the treatment of opioid dependence. A secondary aim compared BI to open-label sublingual buprenorphine/naloxone tablets (BNX). DESIGN: Randomized, double-blind, placebo-controlled trial. Subjects received either four buprenorphine implants (80 mg/implant) (n = 114), four placebo implants (n = 54) or open-label BNX (12-16 mg/day) (n = 119). SETTING: Twenty addiction treatment centers. PARTICIPANTS: Adult out-patients (ages 18-65) with DSM-IV-TR opioid dependence. MEASUREMENTS: The primary efficacy end-point was the percentage of urine samples negative for opioids collected from weeks 1 to 24, examined as a cumulative distribution function (CDF). FINDINGS: The BI CDF was significantly different from placebo (P < 0.0001). Mean [95% confidence interval (CI)] proportions of urines negative for opioids were: BI = 31.2% (25.3, 37.1) and PI = 13.4% (8.3, 18.6). BI subjects had a higher study completion rate relative to placebo (64 versus 26%, P < 0.0001), lower clinician-rated (P < 0.0001) and patient-rated (P < 0.0001) withdrawal, lower patient-ratings of craving (P < 0.0001) and better subjects' (P = 0.031) and clinicians' (P = 0.022) global ratings of improvement. BI also resulted in significantly lower cocaine use (P = 0.0016). Minor implant-site reactions were comparable in the buprenorphine [27.2% (31 of 114)] and placebo groups [25.9% (14 of 54)]. BI were non-inferior to BNX on percentage of urines negative for opioids [mean (95% CI) = 33.5 (27.3, 39.6); 95% CI for the difference of proportions = (-10.7, 6.2)]. CONCLUSIONS: Compared with placebo, buprenorphine implants result in significantly less frequent opioid use and are non-inferior to sublingual buprenorphine/naloxone tablets.

Buprenorphine implants for treatment of opioid dependence: a randomized controlled trial.

CONTEXT: Limitations of existing pharmacological treatments for opioid dependence include low adherence, medication diversion, and emergence of withdrawal symptoms. OBJECTIVE: To determine the efficacy of buprenorphine implants that provide a low, steady level of buprenorphine over 6 months for the treatment of opioid dependence. DESIGN, SETTING, AND PARTICIPANTS: A randomized, placebo-controlled, 6-month trial conducted at 18 sites in the United States between April 2007 and June 2008. One hundred sixty-three adults, aged 18 to 65 years, diagnosed with opioid dependence. One hundred eight were randomized to receive buprenorphine implants and 55 to receive placebo implants. INTERVENTION: After induction with sublingual buprenorphine-naloxone tablets, patients received either 4 buprenorphine implants (80 mg per implant) or 4 placebo implants. A fifth implant was available if a threshold for rescue use of sublingual buprenorphine-naloxone treatment was exceeded. Standardized individual drug counseling was provided to all patients. MAIN OUTCOME MEASURE: The percentage of urine samples negative for illicit opioids for weeks 1 through 16 and for weeks 17 through 24. RESULTS: The buprenorphine implant group had significantly more urine samples negative for illicit opioids during weeks 1 through 16 (P = .04). Patients with buprenorphine implants had a mean percentage of urine samples that tested negative for illicit opioids across weeks 1 through 16 of 40.4% (95% confidence interval [CI], 34.2%-46.7%) and a median of 40.7%; whereas those in the placebo group had a mean of 28.3% (95% CI, 20.3%-36.3%) and a median of 20.8%. A total of 71 of 108 patients (65.7%) who received buprenorphine implants completed the study vs 17 of 55 (30.9%) who received placebo implants (P < .001). Those who received buprenorphine implants also had fewer clinician-rated (P <.001) and patient-rated (P = .004) withdrawal symptoms, had lower patient ratings of craving (P <.001), and experienced a greater change on clinician global ratings of severity of opioid dependence (P<.001) and on the clinician global ratings of improvement (P < .001) than those who received placebo implants. Minor implant site reactions were the most common adverse events: 61 patients (56.5%) in the buprenorphine group and 29 (52.7%) in the placebo group. CONCLUSION: Among persons with opioid dependence, the use of buprenorphine implants compared with placebo resulted in less opioid use over 16 weeks as assessed by urine samples. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00447564.

The Physician Clinical Support System-Buprenorphine (PCSS-B): a novel project to expand/improve buprenorphine treatment.

Opioid dependence is largely an undertreated medical condition in the United States. The introduction of buprenorphine has created the potential to expand access to and use of opioid agonist treatment in generalist settings. Physicians, however, often have limited training and experience providing this type of care. Some physicians believe having a mentoring relationship with an experienced provider during their initial introduction to the use of buprenorphine would ease implementation. Our goal was to describe the development, implementation, resources, and evaluation of the Physician Clinical Support System-Buprenorphine (PCSS-B), a federally funded program to improve access to and quality of treatment with buprenorphine. We provide a description of the PCSS-B, a national network of 88 trained physician mentors with expertise in buprenorphine treatment and skills in clinical education. We provide information regarding the use the PCSS-B core services including telephone, email and in-person support, a website, clinical guidances, a warmline and outreach to primary care and specialty organizations. Between July 2005 and July 2009, 67 mentors and 4 clinical experts reported providing mentoring services to 632 participants in 48 states, Washington DC and Puerto Rico. A total of 1,455 contacts were provided through email (45%), telephone (34%) and in-person visits (20%). Seventy-six percent of contacts addressed a clinical issue. Eighteen percent of contacts addressed a logistical issue. The number of contacts per participant ranged from 1-125. Between August 2005 and April 2009 there were 72,822 visits to the PCSS-B website with 179,678 pages viewed. Seven guidances were downloaded more than 1000 times. The warmline averaged more than 100 calls per month. The PCSS-B model provides support for a mentorship program to assist non-specialty physicians in the provision of buprenorphine and may serve as a model for dissemination of other types of care.

Pharmacists' and technicians' perceptions and attitudes toward dispensing buprenorphine/ naloxone to patients with opioid dependence.

OBJECTIVE: To assess the perceptions and attitudes of pharmacists and pharmacy technicians involved in an office-based opioid dependence treatment program using buprenorphine/naloxone. DESIGN: Cross-sectional attitudinal assessment. SETTING: Community, outpatient hospital, and clinic pharmacies. PARTICIPANTS: Pharmacists and technicians participating in a clinical trial of opioid dependence treatment using buprenorphine/naloxone. INTERVENTION: Written and telephone surveys followed by interviews with open-ended items. MAIN OUTCOME MEASURES: Attitudes and perceptions regarding opioid-dependent patients and use of buprenorphine/naloxone for treatment of opioid dependence. RESULTS: Pharmacies in seven states (New York, Virginia, Illinois, Florida, Texas, California, and Washington) participated in the clinical trial. A total of 40 pharmacists and pharmacy technicians responded to the initial written survey, representing 27 of the 32 pharmacies (84%). Follow-up interviews were obtained from one individual at 30 of those pharmacies (93.8%). Most pharmacy personnel (77.5%) involved with this study were not more concerned about theft or break-ins and would be willing to participate in opioid dependence treatment as the medication became available commercially (70%). The majority of respondents (85%) indicated that patients did not cause problems at their pharmacies. Compared with their experiences in administering other narcotic medications, most respondents did not express increased concern regarding prescription forgery (75%) or diversion (80%) of buprenorphine/naloxone. CONCLUSION: The majority of respondents expressed positive attitudes and perceptions regarding patients treated for opioid dependence with buprenorphine/naloxone.

A placebo-controlled screening trial of olanzapine, valproate, and coenzyme Q10/L-carnitine for the treatment of cocaine dependence.

AIMS: To conduct a medication screening trial on the efficacy of olanzapine, valproate or coenzyme Q10/L-carnitine combination versus placebo for the treatment of cocaine dependence. DESIGN: A four-arm, modified blinded, parallel group study in an out-patient setting using the Cocaine Rapid Efficacy and Safety Trials (CREST) study design. SETTING: The study was performed at the New York Medications Development Research Unit (MDRU). PARTICIPANTS: All participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence and provided at least two urine samples positive for benzoylecgonine (BE) during the 2-week screening period. Sixty-eight participants were enrolled with 39 completing the study. INTERVENTION: After a 2-week screening period, 68 subjects were assigned randomly to receive either olanzapine (10 mg/day), valproate (1500 mg/day), coenzyme Q10 (200 mg/day) and L-carnitine (500 mg/day) combination or placebo for an 8-week treatment period. All subjects also received individual cognitive behavioral counseling during treatment. MEASUREMENTS: Primary outcome measures included quantitative urine benzoylecgonine (BE) levels, self-report of drug use, and global impression scores. Secondary outcomes included cocaine craving, study retention and related psychosocial measures. Safety measures included adverse event monitoring, vital signs, and extrapyramidal side-effects tests. RESULTS: Study retention was similar across all treatment groups, and all groups showed improvement across most measures of treatment efficacy over the duration of the study. None of the study medications, however, were superior to placebo on any of the primary or secondary outcome measures. Cocaine use, as measured by urine BE levels and self-report, was not significantly lower than placebo in any of the drug treatment groups. All study medications were equally well tolerated, and few medication side effects were observed. CONCLUSION: This pilot study does not support the effectiveness of olanzapine, valproate or coenzyme Q10/L-carnitine combination for the treatment of cocaine dependence.

Community treatment programs take up buprenorphine.

Clinicians have been working out ways to incorporate buprenorphine into their treatment models. Representatives of three addiction treatment programs - a Veterans Affairs methadone clinic, a group of outpatient mental health centers, and a nationwide organization of therapeutic communities - talk about their plans and experiences.

Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone.

BACKGROUND: Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone has been proposed, but its efficacy and safety have not been well studied. METHODS: We conducted a multicenter, randomized, placebo-controlled trial involving 326 opiate-addicted persons who were assigned to office-based treatment with sublingual tablets consisting of buprenorphine (16 mg) in combination with naloxone (4 mg), buprenorphine alone (16 mg), or placebo given daily for four weeks. The primary outcome measures were the percentage of urine samples negative for opiates and the subjects' self-reported craving for opiates. Safety data were obtained on 461 opiate-addicted persons who participated in an open-label study of buprenorphine and naloxone (at daily doses of up to 24 mg and 6 mg, respectively) and another 11 persons who received this combination only during the trial. RESULTS: The double-blind trial was terminated early because buprenorphine and naloxone in combination and buprenorphine alone were found to have greater efficacy than placebo. The proportion of urine samples that were negative for opiates was greater in the combined-treatment and buprenorphine groups (17.8 percent and 20.7 percent, respectively) than in the placebo group (5.8 percent, P<0.001 for both comparisons); the active-treatment groups also reported less opiate craving (P<0.001 for both comparisons with placebo). Rates of adverse events were similar in the active-treatment and placebo groups. During the open-label phase, the percentage of urine samples negative for opiates ranged from 35.2 percent to 67.4 percent. Results from the open-label follow-up study indicated that the combined treatment was safe and well tolerated. CONCLUSIONS: Buprenorphine and naloxone in combination and buprenorphine alone are safe and reduce the use of opiates and the craving for opiates among opiate-addicted persons who receive these medications in an office-based setting.