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 16^th 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, 4^th 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%).

Dosing Guide:

• Low Dose = less than 8 mg
• Medium Dose 8 – 24 mg
• High Dose = 24 mg or more

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).

LIMITATIONS

1. 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.
2. 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.

NEXT STEPS

A randomized trial to test whether low buprenorphine doses are as effective as placebo may help determine their overall utility.

BOTTOM LINE

CITATIONS

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.