Patrick G. O’Connor

Emergency Department–Initiated Buprenorphine/Naloxone Treatment for Opioid Dependence: A Randomized Clinical Trial

IMPORTANCE Opioid-dependent patients often use the emergency department (ED) for medical care. OBJECTIVE To test the efficacy of 3 interventions for opioid dependence: (1) screening and referral to treatment (referral); (2) screening, brief intervention, and facilitated referral to community-based treatment services (brief intervention); and (3) screening, brief intervention, ED-initiated treatment with buprenorphine/naloxone, and referral to primary care for 10-week follow-up (buprenorphine). DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial involving 329 opioid-dependent patients who were treated at an urban teaching hospital ED from April 7, 2009, through June 25, 2013. INTERVENTIONS After screening, 104 patients were randomized to the referral group, 111 to the brief intervention group, and 114 to the buprenorphine treatment group. MAIN OUTCOMES AND MEASURES Enrollment in and receiving addiction treatment 30 days after randomization was the primary outcome. Self-reported days of illicit opioid use, urine testing for illicit opioids, human immunodeficiency virus (HIV) risk, and use of addiction treatment services were the secondary outcomes. RESULTS Seventy-eight percent of patients in the buprenorphine group (89 of 114 [95% CI, 70%-85%]) vs 37% in the referral group (38 of 102 [95% CI, 28%-47%]) and 45% in the brief intervention group (50 of 111 [95% CI, 36%-54%]) were engaged in addiction treatment on the 30th day after randomization (P < .001). The buprenorphine group reduced the number of days of illicit opioid use per week from 5.4 days (95% CI, 5.1-5.7) to 0.9 days (95% CI, 0.5-1.3) vs a reduction from 5.4 days (95% CI, 5.1-5.7) to 2.3 days (95% CI, 1.7-3.0) in the referral group and from 5.6 days (95% CI, 5.3-5.9) to 2.4 days (95% CI, 1.8-3.0) in the brief intervention group (P < .001 for both time and intervention effects; P = .02 for the interaction effect). The rates of urine samples that tested negative for opioids did not differ statistically across groups, with 53.8% (95% CI, 42%-65%) in the referral group, 42.9% (95% CI, 31%-55%) in the brief intervention group, and 57.6% (95% CI, 47%-68%) in the buprenorphine group (P = .17). There were no statistically significant differences in HIV risk across groups (P = .66). Eleven percent of patients in the buprenorphine group (95% CI, 6%-19%) used inpatient addiction treatment services, whereas 37% in the referral group (95% CI, 27%-48%) and 35% in the brief intervention group (95% CI, 25%-37%) used inpatient addiction treatment services (P < .001). CONCLUSIONS AND RELEVANCE Among opioid-dependent patients, ED-initiated buprenorphine treatment vs brief intervention and referral significantly increased engagement in addiction treatment, reduced self-reported illicit opioid use, and decreased use of inpatient addiction treatment services but did not significantly decrease the rates of urine samples that tested positive for opioids or of HIV risk. These findings require replication in other centers before widespread adoption. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00913770.

Hypersensitivity pneumonitis induced by intranasal heroin use

locus ceruleus, since experimental bilateral pontine lesions that involve the peri-locus ceruleus produce REM sleep behavior disorder in animals (l6). Bisoprolol is a lipophilic agent that penetrates the blood-brain barrier and blocks pontomedullary b-receptors (3). We conclude that bisoprolol may induce REM sleep behavior disorder and that physicians who prescribe this antihypertensive agent should be aware of this possibility if patients report sleep disturbances shortly after the start of therapy.

Primary care-based ambulatory opioid detoxification: the results of a clinical trial.

OBJECTIVE: To determine the feasibility of primary care-based ambulatory opioid detoxification (AOD) using two protocols: clonidine and clonidine plus naltrexone.SETTING: The Central Medical Unit (CMU)—a freestanding primary care medical clinic staffed by physicians and nurse practitioners.PATIENTS: Injection drug users (IDUs) seeking substance abuse treatment between the ages of 18 and 50 years who were addicted to opioids (e.g., heroin) and not currently in drug treatment.INTERVENTIONS: In the clonidine protocol, clonidine was administered every 4 hours “as needed” for up to 12 days. In the clonidine plus naltrexone protocol, clonidine was administered and naltrexone was administered in increasing doses over five days. Both protocols included “adjuvant” medications for muscle cramps, insomnia, and vomiting. Successfully detoxified patients were referred to ongoing drug treatment.DESIGN: A prospective nonrandomized clinical trial.MEASUREMENTS AND MAIN RESULTS: One hundred forty opioid-addicted IDUs were referred to the medical clinic for AOD. Among the 125 patients who enrolled in the study, 57 selected clonidine and 68 selected clonidine/naltrexone. The treatment groups (clonidine vs clonidine/naltrexone) were similar at baseline with respect to: age at first heroin use (21 years vs 23 years), mean admission opioid craving score (45/100 vs 49/100), and withdrawal symptom score (19/72 vs 18/72). Overall, 70% (88/125) of the AODs were successful, including 42% (24/57) for clonidine and 94% (64/68) for clonidine/naltrexone (p<0.001).CONCLUSIONS: This study suggests that primary care-based AOD can be safely and effectively carried out by primary care providers and that clonidine/naltrexone may be more effective in this setting than is clonidine alone. Ambulatory opioid detoxification can give internists a larger role in initiating drug treatment for IDUs who are addicted to opioids.

Integrating Buprenorphine Treatment into Office-based Practice: a Qualitative Study

BACKGROUNDDespite the availability and demonstrated effectiveness of office-based buprenorphine maintenance treatment (BMT), the systematic examination of physicians’ attitudes towards this new medical practice has been largely neglected.OBJECTIVETo identify facilitators and barriers to the potential or actual implementation of BMT by office-based medical providers.DESIGNQualitative study using individual and group semi-structured interviews.PARTICIPANTSTwenty-three practicing office-based physicians in New England.APPROACHInterviews were audiotaped, transcribed, and entered into a qualitative software program. The transcripts were thematically coded using the constant comparative method by a multidisciplinary team.RESULTSEighty percent of the physicians were white; 55% were women. The mean number of years since graduating medical school was 14 (SD = 10). The primary areas of clinical specialization were internal medicine (50%), infectious disease (20%), and addiction medicine (15%). Physicians identified physician, patient, and logistical factors that would either facilitate or serve as a barrier to their integration of BMT into clinical practice. Physician facilitators included promoting continuity of patient care, positive perceptions of BMT, and viewing BMT as a positive alternative to methadone maintenance. Physician barriers included competing activities, lack of interest, and lack of expertise in addiction treatment. Physicians’ perceptions of patient-related barriers included concerns about confidentiality and cost, and low motivation for treatment. Perceived logistical barriers included lack of remuneration for BMT, limited ancillary support for physicians, not enough time, and a perceived low prevalence of opioid dependence in physicians’ practices.CONCLUSIONSAddressing physicians’ perceptions of facilitators and barriers to BMT is crucial to supporting the further expansion of BMT into primary care and office-based practices.

Primary Care–Based Buprenorphine Taper vs Maintenance Therapy for Prescription Opioid Dependence: A Randomized Clinical Trial

IMPORTANCE Prescription opioid dependence is increasing and creates a significant public health burden, but primary care physicians lack evidence-based guidelines to decide between tapering doses followed by discontinuation of buprenorphine hydrochloride and naloxone hydrochloride therapy (hereinafter referred to as buprenorphine therapy) or ongoing maintenance therapy. OBJECTIVE To determine the efficacy of buprenorphine taper vs ongoing maintenance therapy in primary care-based treatment for prescription opioid dependence. DESIGN, SETTING, AND PARTICIPANTS We conducted a 14-week randomized clinical trial that enrolled 113 patients with prescription opioid dependence from February 17, 2009, through February 1, 2013, in a single primary care site. INTERVENTIONS Patients were randomized to buprenorphine taper (taper condition) or ongoing buprenorphine maintenance therapy (maintenance condition). The buprenorphine taper was initiated after 6 weeks of stabilization, lasted for 3 weeks, and included medications for opioid withdrawal, after which patients were offered naltrexone treatment. The maintenance group received ongoing buprenorphine therapy. All patients received physician and nurse support and drug counseling. MAIN OUTCOMES AND MEASURES Illicit opioid use via results of urinanalysis and patient report, treatment retention, and reinitiation of buprenorphine therapy (taper group only). RESULTS During the trial, the mean percentage of urine samples negative for opioids was lower for patients in the taper group (35.2% [95% CI, 26.2%-44.2%]) compared with those in the maintenance group (53.2% [95% CI, 44.3%-62.0%]). Patients in the taper group reported more days per week of illicit opioid use than those in the maintenance group once they were no longer receiving buprenorphine (mean use, 1.27 [95% CI, 0.60-1.94] vs 0.47 [95% CI, 0.19-0.74] days). Patients in the taper group had fewer maximum consecutive weeks of opioid abstinence compared with those in the maintenance group (mean abstinence, 2.70 [95% CI, 1.72-3.75] vs 5.20 [95% CI, 4.16-6.20] weeks). Patients in the taper group were less likely to complete the trial (6 of 57 [11%] vs 37 of 56 [66%]; P < .001). Sixteen patients in the taper group reinitiated buprenorphine treatment after the taper owing to relapse. CONCLUSIONS AND RELEVANCE Tapering is less efficacious than ongoing maintenance treatment in patients with prescription opioid dependence who receive buprenorphine therapy in primary care. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00555425.

Thrice-weekly versus daily buprenorphine maintenance

BACKGROUND Buprenorphine is a promising alternative to methadone or levo-acetyl alpha methadol for opioid agonist maintenance treatment, and thrice-weekly dosing would facilitate its use for this purpose. METHODS After a 3-day induction, opioid-dependent patients (n = 92) were randomly assigned to daily clinic attendance and 12-weeks maintenance treatment with sublingual buprenorphine administered double blind either daily (n = 45; 16 mg/70 kg) or thrice weekly (n = 47; 34 mg/70 kg on Fridays and Sundays and 44 mg/70 kg on Tuesdays). Outcome measures include retention, results of 3x/week urine toxicology tests, and weekly self-reported illicit drug use. RESULTS There were no significant differences at baseline in important social, demographic, and drug-use features. Retention was 71% in the daily and 77% in the 3x/week conditions. The proportion of opioid-positive urine tests decreased significantly from baseline in both groups and averaged 57% (daily) and 58% in 3x/week. There were no significant differences between groups in self-reported number of bags of heroin used for any day of the week, including Thursdays (48-72 hours following the last buprenorphine dose for subjects in the 3x/week condition), or in medication compliance (92%, 91%) and counseling attendance (82%, 82%). CONCLUSIONS At an equivalent weekly dose of 112 mg/70 kg, thrice-weekly and daily sublingual buprenorphine appear comparable in efficacy with regard to retention and reductions in illicit opioid and other drug use. These findings support the potential for utilizing thrice-weekly buprenorphine dosing in novel settings.

Cost Analysis of Clinic and Office-based Treatment of Opioid Dependence: Results with Methadone and Buprenorphine in Clinically Stable Patients

The cost of providing and receiving treatment for opioid dependence can determine its adoption. To compare the cost of clinic-based methadone (MC, n=23), office-based methadone (MO, n=21), and office-based buprenorphine (BO, n=34) we performed an analysis of treatment and patient costs over 6 months of maintenance in patients who had previously been stabilized for at least 1 year. We performed statistical comparisons using ANOVA and chi-square tests and performed a sensitivity analysis varying cost estimates and intensity of clinical contact. The cost of providing 1 month of treatment per patient was

Social and clinical features as predictors of outcome in outpatient alcohol withdrawal

147 (MC),

Plasma concentrations of buprenorphine 24 to 72 hours after dosing

220 (MO) and

Health system factors and antihypertensive adherence in a racially and ethnically diverse cohort of new users.

336 (BO) (p<0.001). Mean monthly medication cost was