Background

The harmful effects of opioid dependence are well known to ED providers and include overdose, high risk behaviors, and psychosocial instability. Patients with opioid dependence represent a significant proportion of ED visits annually, whether for overdose, addiction/withdrawal treatment, or general medical and psychiatric care. Previous studies have shown that buprenorphine/naloxone, a partial opioid agonist + antagonist, reduces withdrawal, craving and opioid use and is an effective pharmacological adjunct for addiction treatment. ED visits represent a potentially important intervention window to initiate addiction treatment in this population.

Clinical Question

Does ED-initiated buprenorphine coupled with a facilitated primary care follow-up, and follow-up office based buprenorphine treatment increase engagement in addiction treatment services at 30 days compared to a brief intervention in the ED and referral to treatment centers?

Population

Opioid dependent patients, >18 years of age, presenting to a large urban teaching hospital

Intervention

Buprenorphine. Patients received a 10-15 minute brief negotiation interview (BNI) followed by ED-initiated buprenorphine treatment, a scheduled 72 hour follow up at the hospital’s primary care center, followed by 10 weeks of office-based buprenorphine treatment. The BNI for opioid dependence contained 4 components: raise the subject, provide feedback, enhance motivation, negotiate and advise

Control

Two groups:
1. Referral: patients received a handout with names, locations and telephone numbers of treatment addiction services and were given telephone access to call a facility of their choice
2. Brief Intervention and Referral: patients received a BNI followed by a list of treatment addiction services. A research associate then directly linked the patient with the referral after reviewing the patient’s eligibility for services, insurance clearance. Transportation was arranged to the facility.

Outcomes

(Primary): Engagement in formal addiction treatment on the 30th day following randomization. This information was gathered by directly calling a facility or clinician to confirm a subject’s engagement in services.
(Secondary): Self-reported number of day of illicit opioid use, HIV risk-taking behavior, use of addiction treatment services- all on the 30th day after randomization.

Design

Randomized control trial- patients were randomly assigned in a 1:1:1 ratio to 1 of 3 groups using a computerized stratified randomization procedure.

Excluded

Non-English speaking, critically ill, unable to communicate due to dementia or psychosis, suicidal, in police custody, current enrollment in formal addiction treatment, medical or psychiatric condition requiring hospitalization, required opioid medication for a pain condition.

Primary Results

(listed in the following order: buprenorphine, brief intervention, referral)

  • Engagement in formal addiction treatment at 30 days: 78% (95% CI, 70-85%) vs. 45% (95% CI, 36-54%) vs. 37% (95% CI, 28-47%), p=<0.001
    • Difference of 33% for buprenorphine vs. brief intervention
    • Difference of 41% for buprenorphine vs. referral
  • Difference in mean # of days of illicit opioid use per week at 30 days: p=<0.001
    • Buprenorphine: 5.4 days (95% CI, 5.1-5.7) to 0.9 (95% CI, 0.5-1.3)
    • Brief Intervention: 5.6 days (95% CI, 5.3-5.9) to 2.4 (95% CI, 1.8-3.0)
    • Referral: 5.4 days (95% CI, 5.1-5.7) to 2.3 (95% CI, 1.7-3.0)
  • Rates of opioid negative urine toxicology screen did not significantly differ across the groups
  • HIV risk behaviors: patients in all 3 groups reported significantly reduced HIV risk behaviors from baseline but this difference was not statistically significant between the 3 groups
  • Decrease in the rate of inpatient addiction treatment services in buprenorphine compared with others: 11% (95%CI, 6-19% vs. 35% (95% CI, 25-37%) vs. 37 (95%CI, 27-48%), p=<0.001
  • No significant difference in mean number of ED visits for addiction treatment across all 3 groups
  • Post-hoc analysis that included only patients who presented to ED specifically seeking treatment for opioid dependence- rates of treatment engagement at 30 days were still higher in buprenorphine group as compared to others

Strengths

  • Study targeted a vulnerable population with frequent ED visits and potential for meaningful intervention
  • Many of the outcome measures were objective reducing bias
  • Follow up was ~99% for primary outcome

Limitations

  • Poor follow up for secondary outcomes
  • Non-blinded for secondary outcomes

Other Issues

  • Unclear separation of interventions- ex: the buprenorphine group had multiple components to it’s intervention in addition to buprenorphine including a brief intervention counseling, follow up with primary care in 72 hours, and 10 weeks of office-based buprenorphine treatment
  • No mention of adverse events associated with buprenorphine/naloxone use such as mortality, overdose or other adverse drug events
  • Did not assess compliance with buprenorphine therapy
  • All interventions and follow up were paid for by the study and did not take into account subject’s insurance eligibility which could impact engagement in treatment

Author's Conclusions

“…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.”

Our Conclusions

While ED-initiated buprenorphine poses a potentially beneficial treatment option for opioid users this study only promotes it’s use when prescribed in conjunction with other meaningful interventions such as: a brief psychosocial interview (BNI), facilitated referral to a primary care clinic, and continuous office-based buprenorphine treatment. All of these interventions are costly and go beyond the current standard of care- it is impossible to know from this study which of those interventions was the most meaningful. While this intervention did significantly increase engagement in addiction treatment at 30 days and self-reported decrease in mean number of days of opioid use per week, this study failed to demonstrate that those outcomes translated into a decrease in health-harming behaviors such as HIV risk behavior or overdoses. Addiction treatment exists on a continuum and in addition to pharmacological intervention, patients need maintenance therapy and psychosocial support, without linking patients to those services, simply prescribing a medication is likely to have little impact. D’Onofrio et al did a good job of combining buprenorphine treatment with those appropriate follow up measures.

Potential Impact To Current Practice

ED visits represent a potentially important invention point for opioid dependent patients and this study suggests a starting point for thinking about ways to intervene that go beyond the current standard of practice.

Bottom Line

The efficacy of buprenorphine for opioid addiction has been well-studied but it’s safety and efficacy when initiated in the ED setting still remains unclear.

Read More

Substance Abuse and Mental Health Services Administration: Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction: http://www.ncbi.nlm.nih.gov/books/NBK64245/?report=reader