In this multi-site study, the first large randomized, controlled trial of patients dependent upon prescription opioids, the rate of unsuccessful outcomes following buprenorphine-naloxone taper, even after a 12-week treatment, was extraordinarily high, exceeding 90%. In contrast, patients stabilized on buprenorphine-naloxone had considerably better opioid use outcomes than those who had been tapered off the medication. Importantly, the addition of individual opioid dependence counseling to buprenorphine-naloxone plus medical management did not improve opioid use outcomes. The extremely high rate of unsuccessful outcomes following burenorphine-naloxone taper is notable in light of the good prognostic characteristics42
of the population (i.e., largely employed, well-educated, relatively brief opioid use histories, and little other current substance use), and prior research suggesting that patients dependent upon prescription opioids might have better outcomes than those dependent upon heroin.9
The number of psychiatric serious adverse events in the post-taper period was low, similar to other studies of opioid-dependent patients;40
nevertheless, physicians should monitor psychiatric symptoms when tapering these patients from opioids.
Our findings suggest that physicians can successfully treat many patients dependent upon prescription opioids, with or without chronic pain, using buprenorphine-naloxone with relatively brief weekly medical management visits; half of our sample did well during this 12-week regimen. Consistent with results from a previous study of predominantly heroin-dependent patients receiving buprenorphine-naloxone in a primary care setting,15
individual drug counseling did not improve opioid use outcomes when added to weekly medical management visits. Like that study, we did not include a condition providing infrequent or no medical management. It is unknown whether providing less intensive medical management, perhaps in conjunction with group counseling, would affect outcomes, which is of particular interest because not all physicians treating opioid dependence with buprenorphine see patients as often as weekly.7
Conversely, more frequent opioid drug counseling, such as that provided in an intensive outpatient treatment program, might have produced better outcomes than did SMM+ODC. Moreover, alternative models of behavioral intervention, e.g., contingency management,43
might improve outcomes in this population, given that approximately half of those receiving buprenorphine-naloxone stabilization did not achieve successful outcomes.
The length of our trial may have influenced our results as well. Studies of methadone maintenance treatment with heroin dependent patients have shown that patients who participate in longer-term treatment (e.g., a year or more) have better outcomes.44, 45
It is not known, however, whether SMM+ODC would have outperformed SMM if delivered for a longer period of time. Moreover, it is unclear whether a taper following longer treatment with buprenorphine-naloxone would yield a better outcome.
Our finding regarding the substantial drop in the rate of successful outcomes in Phase 2 that occurred following the buprenorphine-naloxone taper must be interpreted with some caution, because the study design did not include a control group of patients who were not tapered. However, this concern is mitigated by the aforementioned evidence from the literature regarding treatment of opioid dependence, which has consistently demonstrated the benefit of longer-term opioid agonist treatment.44, 45
Interestingly, the presence of chronic pain did not influence opioid use outcomes. Chronic pain is highly prevalent in patients dependent upon prescription opioids46–48
and was present in nearly half of our study population, albeit of relatively moderate intensity overall. Indeed, if treating physicians deemed their patients’ pain to be severe enough to require ongoing opioid therapy, they were excluded from the study. It is not known whether our findings can be generalized to patients with severe pain or patients seeking treatment for pain rather than for opioid dependence. Previous research had shown that individuals with co-occurring pain and substance dependence appear to respond poorly to addiction treatment24
except in the context of opioid maintenance therapy.49
This was the first study, however, to examine this topic prospectively in a population comprised exclusively of those dependent upon prescription opioids. The negative prognostic impact of even minimal lifetime heroin use on outcome while maintained on buprenorphine-naloxone was notable, especially since we excluded those with substantial heroin use histories, including any heroin injection. It is unclear whether this was attributable to heroin use itself, population differences, or some other factor.
Strengths of the study include the large, national, multi-site study sample and the broad inclusion criteria, including patients both with and without chronic pain. Consistent with other opioid dependence treatment studies,15, 40
our study was limited by the high dropout rate from Phase 1 to Phase 2, although dropout rate did not vary by treatment condition.
The study has important implications for clinical practice. The lack of a difference between SMM and SMM+ODC was similar to the finding of Fiellin et al.15
with a largely heroin-dependent population, despite the fact that we had a greater contrast in intensity of counseling conditions than that study. This supports the national trend toward treatment of opioid dependence by physicians in office-based practice.7
Further, patients dependent upon prescription opioids, with or without chronic pain, are most likely to reduce their opioid use during the first several months of treatment while receiving buprenorphine-naloxone; if tapered off this medication, the likelihood of relapse to opioid use or dropout from treatment is overwhelmingly high. Our findings raise an important question: what length of buprenorphine-naloxone treatment, if any, would lead to substantially better outcomes after a taper? This is a topic of clinical and research interest.