Dosing of Suboxone & Opioid Dependency Treatment Outcomes
Buprenorphine (often prescribed in a combined formulation with naloxone, under the brand name “Suboxone”) has received much attention as an evidence-based medication-assisted treatment for individuals with opioid use disorder. However, some questions remain about its effectiveness at lower doses.
Do individuals have similar outcomes regardless of their buprenorphine dose? Or does buprenorphine dose factor into patient outcomes?
WHAT PROBLEM DOES THIS STUDY ADDRESS?
Buprenorphine (Suboxone) is effective in reducing opioid use short term relative to placebo particularly at higher doses. To illustrate, studies have shown overall that, relative to placebo, the average buprenorphine patient would be using opioids far less often (at about the 16th percentile in the placebo group in terms of opioid use).
This benefit is true when patients are followed up longer term as well. This particular study took a closer look at the earliest days of buprenorphine treatment, also called the “induction” period. This is the time when doctors initially start an individual on a medication. Clinical research on this induction period, like in the current investigation, can help practitioners understand whether there are clinical decisions during these early critical days that impact how individuals fare later on while taking buprenorphine to help prevent illicit opioid use.
HOW WAS THIS STUDY CONDUCTED?
This study analyzed data from a large trial of buprenorphine (Suboxone) compared to methadone, to evaluate their safety when used in real-world settings (see here for more information on this trial, and a comparison of the two medications over several years). The researchers examined just the 740 who were randomized to the buprenorphine group in that trial, all of whom had opioid dependence based on criteria from the diagnostic and statistical manual of mental disorders, 4th edition (DSM-IV).
On average, the sample was 37 years old, and used opioids 27 of 30 days before they entered the study. Most were male (90%) and White (95%).
- Low Dose = less than 8 mg
- Medium Dose 8 – 24 mg
- High Dose = 24 mg or more
Researchers used a sophisticated statistical approach to identify six groups of individuals based on their initial buprenorphine (Suboxone) dose during induction, and how it changed over 4 weeks, the time experts believe it takes to stabilize a buprenorphine dose.
- Group 1: started and remained on low dose (n = 180)
- Group 2: started on low dose and shifted gradually to moderate dose (n = 50)
- Group 3: started on low dose and shifted quickly to a moderate dose (n = 217)
- Group 4: started on moderate dose and shifted to a low dose (n = 54)
- Group 5: started and remained on moderate dose (n = 111)
- Group 6: started on moderate dose and shifted to high dose (n = 114)
The groups were then compared on treatment drop-out, opioid use, and adverse events as outlined above over the 6 months during which they were enrolled in the study. These analyses comparing groups also controlled statistically for several variables at once that were related to the groups, and that one might think would also be related to these treatment outcomes.
This helped to increase the likelihood that any advantage or disadvantage found for one of the groups was caused by their different initial buprenorphine (Suboxone) dosing pattern. These included both demographic characteristics (e.g., gender) and clinical variables, including whether or not they injected opioids.
WHAT DID THIS STUDY FIND?
Jacobs and colleagues found that how someone is initially started and stabilized on buprenorphine (Suboxone) in a real-world treatment setting is related to treatment outcomes, but only in some respects.
Generally, there are few differences in how individuals fare in Suboxone treatment based purely on their dose. One exception is that those on higher doses (e.g., 16mg or more) are more likely to remain in treatment during the 1st month.
In comparing groups of individuals receiving different doses of buprenorphine, individuals on higher doses (e.g., 16 or more mg) during the first month of the 6-month treatment were less likely to drop out of treatment.
However, someone’s buprenorphine (Suboxone) dose was not related to drop-out during the last month of treatment. Someone’s buprenorphine dose was generally unrelated to how often they used illicit opioids during the study. One exception was that individuals stably on a moderate dose (8-24mg) used illicit opioids on fewer days during the last month than those stably on a low dose, although this difference was not large (about 1 day of opioid use in a month).
Buprenorphine use was generally unrelated to negative health outcomes from the medication itself. In fact, those on a higher dose may be at lower risk for medication-related adverse events during the initial month.
Not surprisingly, individuals who took longer to achieve a stable dose, defined as the highest dose a patient took for greater than 1 month, had more opioid use days during the last month of treatment. These individuals may be more complicated from a clinical perspective, contributing both to the difficulty establishing a stable dose, and to their poorer outcomes. How quickly they achieved this stable dose, on the other hand, was unrelated to treatment drop-out or adverse events.
WHY IS THIS STUDY IMPORTANT
The study examined differences in outcomes based on dosing patterns of individuals with opioid use disorder in medication-assisted treatment with buprenorphine (Suboxone).
Clinically it may be worth starting individuals at a higher dose, & maintaining that dose or lowering it over time if indicated. This practice could help initially engage patients in Suboxone treatment which prior studies suggest increases someone’s likelihood of opioid abstinence over time.
In fact, while there is general consensus that buprenorphine treatment is one clinical strategy to reduce relapse and overdose risk among those with opioid use disorder, a combined review of several studies (meta-analysis) suggests buprenorphine may only be more effective at reducing opioid use than placebo at these higher doses (see here).
- This study compared groups of patients based on their buprenorphine dose patterns, but they were not randomized to groups. The researchers’ made efforts to rigorously account and control for factors that could be related both to buprenorphine dose and treatment outcomes, such as how clinically severe they were when they first entered the study. Nevertheless, in the absence of a randomized design, as the study authors noted, there always remains a degree of uncertainty around whether any differences in group outcomes were caused by the group differences themselves.
- Also as noted, these individuals received their buprenorphine (Suboxone) as part of a daily dose at the outpatient treatment program. As some may know, buprenorphine is not often prescribed this way; one of its advantages relative to methadone is the ability to send patients home with 1 week or more of medication. Greater monitoring overall could have a number of implications, including reducing any potential effects of higher doses, as well as reducing the likelihood of adverse events, such as taking more study medication than prescribed.
A randomized trial to test whether low buprenorphine doses are as effective as placebo may help determine their overall utility.
- For Individuals & families seeking recovery: Individuals with opioid use disorder are unlikely to be harmed by higher doses of buprenorphine prescribed and monitored by a licensed physician with addiction treatment expertise. Nor, however, are they likely to have better opioid use outcomes than those on lower buprenorphine doses early on. That said, doses about 16mg or more may help you remain in treatment early on, because it helps lower withdrawal symptoms and cravings relative to doses less than 16mg.
- For Scientists: This study used latent class analysis to identify six trajectories of buprenorphine dosing in those randomly assigned to this condition in a multisite randomized controlled trial (see below for more information). Controlling for propensity scores associated with these dosing patterns, study analyses tended to find few differences among the groups on treatment retention or outcomes, including adverse events. Future studies might use a controlled design to compare these dosing patterns, rather than a secondary analysis, which despite the strong design, still leaves open some questions of causality.
- For Policy makers: Given the data from this study as well as formative meta-analysis suggesting only buprenorphine doses above 16 mg may only be more effective than placebo, consider funding controlled trials to investigate whether doses below 16mg can be effective.
- For Treatment professionals and treatment systems: Because individuals in this study had generally similar outcomes irrespective of buprenorphine dose, including adverse events, consider starting individuals at a higher dose (16mg or greater) to increase their chances of initial treatment engagement.
Jacobs, P., Ang, A., Hillhouse, M. P., Saxon, A. J., Nielsen, S., Wakim, P. G., … & Blaine, J. D. (2015). Treatment outcomes in opioid dependent patients with different buprenorphine/naloxone induction dosing patterns and trajectories. The American Journal on Addictions, 24(7), 667-675.