Naloxone is not absorbed in sublingual form and serves only to deter IV diversion of buprenorphine. Induction with buprenorphine alone is reserved for patients with documented allergy to naloxone or who are being detoxified from long-acting opiates such as methadone.
Dosing strategies are identical for both formulations. The usual starting dosage is 4 mg once daily, with a maximum dosage of 32 mg/d (Table). Withdrawal symptoms are typically controlled with 12 to 24 mg/d.14
If the patient is in active opiate withdrawal, the starting dose usually relieves symptoms in 30 to 45 minutes. If not, a second 4-mg dose can be given. Most patients do not require >8 mg the first day, but some may require 16 to 24 mg to suppress withdrawal symptoms.15
Some clinicians—such as solo practitioners who lack the resources of an outpatient clinic—prefer to have the patient take the first dose at home. Patients are instructed to take the first dose after withdrawal symptoms begin and to repeat the dose in 1 hour if symptoms persist. Thus, patients titrate their own dosages, but the clinician must be immediately available to handle complications. Induction continues until withdrawal symptoms are controlled.
The next day, patients return for evaluation. An objective scale such as the 11-item COWS can quantify withdrawal symptom severity.16 For each symptom—heart rate, nausea, diaphoresis, or restlessness—the COWS assigns a number corresponding to its severity. A total score >25 indicates moderately severe withdrawal.
After withdrawal symptoms are controlled, follow-up visits are scheduled every 2 to 3 days the first week and then weekly. Some physicians maintain daily contact with patients via e-mail or telephone to track symptoms.
Case continued: Steady improvement
By day 3, Mr. T gradually increased his buprenorphine/naloxone dosage to 16 mg once daily. He continued that dosage for 10 days before his next visit. At that point, he was slightly anxious but physically comfortable. He came into the office on days 2, 5, and 10 and his COWS scores decreased each time.
Stabilization and maintenance
When withdrawal symptoms are stabilized, patients begin maintenance therapy at the dosage that stabilized their symptoms. During maintenance therapy, the average buprenorphine dosage is 16 to 24 mg/d. Because of its long half-life, buprenorphine can be taken once daily, though some patients prefer twice-daily dosing for psychological comfort. Several studies comparing buprenorphine with methadone have found that buprenorphine, 8 to 16 mg/d, is similar in effect to approximately 60 mg/d of methadone.5
During the maintenance phase, it is important to have a policy for patients who relapse to substance abuse while taking buprenorphine (Box 2). During buprenorphine maintenance treatment, the estimated relapse rate to opiate use (chance of one positive test for opiates) ranges from 20% to 60%, compared with a relapse rate of 80% to 90% seen with placebo during clinical trials.5
Case continued: Time to taper?
After taking buprenorphine 2 months, Mr. T wants to taper off. He has been seen weekly and receives individual psychotherapy and group counseling. All urine drug screens have been negative for opiates.
With the psychiatrist’s observation, Mr. T. begins to taper his dosage of 16 mg/d by 4 mg a week. He is comfortable when he reaches 4 mg/d, but notices increased anxiety and general achiness when he reduces buprenorphine to 2 mg/d. He elects to remain at 4 mg/d for another 2 months.
Discontinuation
After the patient has reached a stable dose of buprenorphine, the clinician and patient together consider two treatment options:
- sustain the dose as maintenance therapy
- or taper and discontinue buprenorphine.
Tips for prescribing buprenorphine
Screening
Screen patients for alcohol or benzodiazepine use, which may trigger symptoms similar to opiate withdrawal (buprenorphine does not treat withdrawal from these substances)
Induction
Worsening symptoms with buprenorphine indicate that withdrawal was precipitated; repeat buprenorphine dosing until symptoms are relieved (do not exceed 24 mg the first day)
Tell patients:
- to wait as long as possible before taking the first dose to reduce risk of precipitating withdrawal
- not to swallow the sublingual tablet, as this inactivates the medication
- the tablet can take 5 minutes or more to dissolve under the tongue
Maintenance
Set a policy for patients who relapse to substance use while taking buprenorphine. Consequences may include immediate buprenorphine cessation, transfer to methadone treatment, re-induction of buprenorphine, or referral to an inpatient substance abuse treatment center
Tracking
Log how many of your patients are taking buprenorphine; you may not treat more than 30 at a time
Patients who have had multiple relapses and endured severe opiate withdrawal might consider remaining on buprenorphine for several months before tapering. Mild opiate withdrawal may occur if buprenorphine is tapered too rapidly, though this is not as severe or distressing as a full agonist withdrawal.