Among patients dependent on prescription opioids, ongoing maintenance therapy using a legal opiate substitute (buprenorphine–naloxone) produced better outcomes than tapered withdrawal, with patients less likely to have used illicit opioids and considerably more likely to have remained in their allocated treatment.
Summary Drug overdose is a leading cause of accidental death in the United States, with most of these deaths due to prescription opioids (
1 2). However, limited research data is available to guide the decisions that physicians and patients routinely make between facilitating medication-assisted withdrawal from opioids (also known as ‘tapering’) and ongoing maintenance treatment.
Studies with patients dependent on heroin have demonstrated improved outcomes with methadone maintenance therapy compared with methadone taper (
3 4), including reduced mortality, risk of HIV transmission, and criminal behaviour (
5 6
7). Patients dependent on prescription opioids can differ in important ways, however, often having shorter histories of opioid dependence, lower levels of physical dependence, better occupational and social functioning, and improved treatment outcomes (
8 9 10 11) – leading to questions about whether they might require ongoing maintenance treatment or might instead benefit more from shorter-term taper followed by continued counselling and treatment with the ‘opioid-blocking’ drug naltrexone.
To aid the development of evidence-based guidelines for patients dependent on prescription opioids, the featured study compared medication-assisted withdrawal using buprenorphine with buprenorphine maintenance treatment in a primary care setting, assessing the subsequent illicit use of prescription opioids.
A tablet formulation of buprenorphine–naloxone was used in a 4:1 ratio of buprenorphine hydrochloride to naloxone hydrochloride. [If taken as intended, the naloxone component remains inactive, and is there to deter misuse, any injecting, or diversion of the medication to other people.]
For all patients, treatment started with a two-week induction and stabilisation period, at a target dose of 16 mg of buprenorphine hydrochloride per day (though the average in practice was 15 mg per day). During this time, patients underwent evaluation and education by nurses in brief (5–10 minute) sessions, three times a week.
After the induction and stabilisation period, patients were assigned at random to receive gradual withdrawal or maintenance therapy.
Patients assigned to the taper group:
• were offered a stable dose of buprenorphine–naloxone for an additional four weeks followed by a gradual taper (2 mg decrease every three days) for three weeks;
• were provided prescriptions to use for opioid withdrawal symptoms (including anti-sickness medication and a sleeping aid).
Those who achieved seven days or more of opioid abstinence after their last dose of buprenorphine were also offered oral naltrexone (25 mg on day one, followed by 50 mg per day). The availability of injectable naltrexone was discussed with these patients.
Patients assigned to the maintenance condition:
• were offered a further 14 weeks maintenance prescribing of buprenorphine–naloxone at doses which could be raised to 20 or 24 mg per day depending on patient comfort or evidence of ongoing (for three successive weeks) illicit opioid use.
All patients received physician and nurse support and drug counselling.
Main findings
On average patients allocated to the tapering programme left treatment sooner than those allocated to maintenance (staying 58 vs. 99 days after randomisation).
Overall, patients assigned to receive a buprenorphine–naloxone taper were less likely to submit urine samples indicative of abstinence from illicit opioids than patients assigned to buprenorphine–naloxone maintenance (35% vs. 53%).
Analyses conducted after seeing the data [performed to see
where statistically significant differences occurred] indicated that patients in the taper and maintenance groups had similar percentages of urine samples testing ‘negative’ for opioids during the first seven weeks of the trial when all patients were receiving medication (46% vs. 49%), but not during the last seven weeks when patients in the taper group were no longer receiving buprenorphine–naloxone and became less likely to submit samples indicative of abstinence from illicit opioids (33% vs. 64%).
Further analyses conducted after seeing the data indicated that during the first seven weeks of the trial patients in the taper and maintenance groups reported a similar average number of days per week of illicit opioid use (1.08 vs. 0.97 days); in contrast, self-reported illicit opioid use differed during the last seven weeks (1.27 vs. 0.47 days). Patients assigned to the taper group achieved fewer average maximum consecutive weeks of opioid abstinence than those assigned to the maintenance group – the average period of abstinence was three vs. five weeks.
Patients in the taper group were more likely to require protective transfer (16 of 57 vs. 3 of 56) at the end of the first six weeks of the study for ‘persistent relapse’, defined as more than two consecutive weeks of daily opioid use and urine samples testing ‘positive’ for opioid use. A study doctor worked with these participants to identify a clinically appropriate treatment plan, for example referral for methadone maintenance therapy, inpatient or intensive outpatient treatment, or for participants assigned to buprenorphine taper, resuming buprenorphine therapy using the initial induction procedure.
In outcomes specific to the taper group, two patients accepted prescriptions for naltrexone, and 16 patients re-initiated buprenorphine therapy.
The authors’ conclusions
The buprenorphine taper resulted in fewer urine samples testing ‘negative’ for opioids, more days of illicit opioid use, fewer weeks of continuous abstinence, and poorer retention in treatment. Very few patients undergoing buprenorphine taper initiated naltrexone therapy or completed treatment, and 28% required reinitiation of buprenorphine therapy owing to relapse after their buprenorphine dose started to taper off.
Based on these findings, medication-assisted withdrawal using a buprenorphine–naloxone taper should be used sparingly (if at all) in primary care for patients who are dependent on prescription opioids; and given the established efficacy of maintenance treatment with methadone and buprenorphine–naloxone, expanded use of maintenance therapy should be the primary response to chronic and relapsing dependence on prescription opioids.
Policies that restrict access to, create financial burdens for, or place arbitrary limits on the duration of maintenance treatment should be reconsidered in the face of evidence that medication tapers lead to relatively poor outcomes (
12 13 14 15 16).
Source :
http://findings.org.uk/
