This article is more than 5 years old. Information may no longer be current.

Buprenorphine yields lower mortality risk during first weeks of opioid substitution therapy

Individuals receiving buprenorphine had lower mortality risk during the first 4 weeks of opioid substitution therapy compared with those receiving methadone; however, there was little difference between the two treatments thereafter.

“Methadone and buprenorphine, two opioid substitution pharmacotherapies, are WHO essential medicines. As a partial opioid receptor agonist, buprenorphine is less likely to induce respiratory depression than is methadone, and might pose a lower risk of opioid overdose, especially during treatment induction or unsanctioned opioid use during opioid substitution therapy,” Jo Kimber, PhD, of the National Drug and Alcohol Research Centre, Randwick, Australia, and colleagues wrote. “To date, however, no well powered studies have been done to directly compare the mortality risks in different periods in and out of treatment for these two medications for use in opioid substitution therapy, nor to compare in-treatment switching between buprenorphine and methadone.”

Researchers conducted a retrospective cohort study of 32,033 patients with opioid dependence who started methadone or buprenorphine treatment from August 2001 to December 2010 in New South Wales, Australia. There was a median follow-up of 6.7 years per person.

Individuals who initiated treatment with buprenorphine had lower all-cause (adjusted RR = 2.17; 95% CI, 1.29-3.67) and drug-related (aRR = 4.88; 95% CI, 1.73-13.69) mortality during the first four weeks of treatment compared with those who initiated treatment with methadone.

Drug-related mortality risk did not differ between treatment groups for the remainder of treatment (aRR = 1.18; 95% CI, 0.89-1.56), though researchers found weak evidence that all-cause mortality risk was lower among the buprenorphine group compared with the methadone group (RR = 1.66; 95% CI, 1.4-1.96).

Four weeks after treatment cessation, all-cause mortality did not differ (aRR = 1.12; 95% CI, 0.79-1.59); however, individuals who initiated with methadone had lower drug-related mortality compared with those who initiated with buprenorphine (aRR = 0.5; 95% CI, 0.29-0.86).

Individuals who switched from buprenorphine to methadone during treatment had lower mortality during the first 4 weeks of methadone treatment compared with matched controls who received methadone only, with a crude mortality rate of 7.1 per 1,000 person-years.

There was no difference in mortality when switching from buprenorphine to methadone or for switches to either medication beyond the first 4 weeks of treatment.

“Clinicians providing opioid substitution treatment face an important dilemma: which is more likely to reduce patient risk, buprenorphine or methadone? Buprenorphine is argued to have a superior safety profile to methadone but also has a higher dropout rate. Our data suggest that induction of patients on to buprenorphine has clear benefits in settings in which risk of death is elevated in the first 4 weeks of treatment, such as Australia and the U.K., but thereafter little evidence exists for any difference in mortality risk or dangers in switching opioid substitution therapy. This finding has direct clinical relevance to clinicians, patients and policy makers worldwide,” the researchers concluded. – by Amanda Oldt

Disclosure: Kimber reports no relevant financial disclosures. Please see the full study for a list of all authors’ relevant financial disclosures.