After 10 years of heroin dependence, Mr. T, age 36, calls your office and says, “I want to get off heroin.” For 8 months, he’s been using IV heroin 2 to 3 times daily. He says he has tried methadone treatment but found daily dosing cumbersome.
He found your office number on the Substance Abuse and Mental Health Services Administration Web site, which lists physicians qualified to prescribe buprenorphine for opiate detoxification. He has heard about “bup” on the street and wants to know if he is eligible and what he can expect from treatment.
Like Mr. T, 1 million Americans are addicted to opiates.1 As qualified physicians gain experience with using buprenorphine, this agent could revolutionize how opiate-dependent patients are routinely treated. Instead of receiving methadone only in specialized clinics, they can now choose to be treated in physicians’ offices.
Several obstacles, however, are preventing widespread buprenorphine use:
- Too few physicians are trained to offer this office-based treatment.
- Many of the 2,000 doctors who are trained remain uncertain about using buprenorphine.
This article is intended to help overcome obstacles to opiate-dependence treatment by familiarizing psychiatrists—whether trained or not in using buprenorphine—with evidence of this agent’s efficacy and its advantages compared with other treatments.
Efficacy and obstacles
Buprenorphine is a partial opioid agonist that binds to the mu receptor (Box 1).2-5 It is a controlled substance (schedule-III narcotic). Outpatient trials have shown that buprenorphine is more effective than placebo and as effective as methadone for opiate detoxification.6-10
In one of the largest trials, 326 opiate-dependent outpatients were randomly assigned to buprenorphine, buprenorphine/naloxone combination, or placebo for 4 weeks. Both buprenorphine forms were more effective than placebo, as measured by clean urine samples and patient reports of reduced opiate cravings.7
In maintenance treatment, buprenorphine has been shown to be more effective than placebo and as effective as methadone, 60 mg/d, in preventing relapse. In a randomized comparison study, 220 opiate-dependent patients received levomethadyl acetate (LAAM), 75 to 115 mg three times a week; buprenorphine, 16 to 32 mg three times a week; high-dose methadone (60 to 100 mg/d); or low-dose methadone (20 mg/d). Subjects reported using opiates 20 to 30 times in the week before study enrollment. After 17 weeks, treatment retention rates were 58% for buprenorphine, 73% for high-dose methadone, and 20% for low-dose methadone. At the same point, urine samples were negative for opiate use in 40% of patients receiving buprenorphine compared with 39% of those receiving high-dose methadone.10
How buprenorphine works
Buprenorphine is a partial opioid agonist derived from thebaine, an anodyne alkaloid from opium. It binds tightly to the muopiate receptor and produces expected opiate effects such as analgesia and mild euphoria.2 Its partial agonist properties create a ceiling effect and thus a lower likelihood of overdose than with opioid agonists.3
Pharmacokinetics
Buprenorphine has low bioavailability, but its 24- to 60-hour half-life allows once-daily dosing. Because common urine drug screens cannot detect buprenorphine, its use does not cause positive tests for opiates or morphine. Overdose risk is minimal when taken sublingually, with no respiratory depression reported in clinical trials.3,4 The drug is metabolized by the cytochrome P-450 3A4 isoenzyme system and demethylated to norbuprenorphine, which is not significantly bioactive.
Side effects
Nausea, fatigue, constipation, and occasional dysphoria
Abuse potential
Euphoria is less likely with buprenorphine than with opioid agonists because of buprenorphine’s ceiling effects. Theoretically, buprenorphine can be abused by being crushed and injected. The buprenorphine/naloxone combination, if taken parenterally, precipitates opiate withdrawal and thus is preferred for most patients with opioid dependence.
Buprenorphine may be fatal when abused, especially in combination with CNS depressants such as alcohol or high-dose benzodiazepines. However, buprenorphine’s mortality risk remains lower than that of methadone.5
Special precautions
Buprenorphine may precipitate opiate withdrawal during induction when an opioid agonist remains bound to the opiate receptor. Buprenorphine will displace the opiate from the receptor, creating an imbalance in opiate binding that the body interprets as opiate withdrawal.2
To avoid withdrawal, tell the patient not to start buprenorphine until mild withdrawal symptoms occur. In case of withdrawal, tell the patient to continue taking buprenorphine until symptoms are relieved. Adjunctive medications such as benzodiazepines, antiemetics, and antidiarrheals also can be given to control symptoms.
Table
Buprenorphine: A typical dosing strategy
| Phase | Dosage* | Comment |
|---|---|---|
| Induction | Maximum dosage is 32 mg/d; 12 to 24 mg/d typically controls withdrawal symptoms | |
| Day 1 | 4 mg bid (total 8 mg) | |
| Day 2 | 12 mg qd | |
| Day 3 | 16 mg qd | |
| Maintenance | 16 to 24 mg/d is average stabilization dosage | Consider severity of withdrawal symptoms and duration of addiction when deciding when to begin discontinuation |
| Discontinuation | Taper dosage by 2 to 4 mg every 3 to 5 days, then discontinue | Most patients remain on final 2 mg/d at least 1 week; consider alternate-day dosing for patients who experience side effects when attempting to reduce from 2 mg/d to 0 mg/d |
| * Buprenorphine/naloxone is preferred formulation | ||