How Important is Suboxone Medication Adherence?

Buprenorphine, often prescribed with naloxone under the brand name Suboxone, is an evidence-based medication for people with opioid use disorder. Clinical wisdom suggests staying on the medication consistently is important to patient outcomes. But does consistent adherence really make a difference?

 WHAT PROBLEM DOES THIS STUDY ADDRESS?

As outlined in another highlighted article in this issue of the Recovery Bulletin, buprenorphine (Suboxone) is an effective medication-assisted treatment for opioid use disorder, especially at doses 16 mg or greater. This is also true over the long term, as individuals receiving buprenorphine treatment in one study example, had 8 fewer days of opioid use each month, on average, across a 5-year follow-up compared to individuals on no medication-assisted treatment.

Although there are not many naturalistic studies of patients in real-world buprenorphine (Suboxone) treatment, the studies that have been done suggest 50-90% will be in treatment 12-18 months later (see here). In this study, Lo-Ciganic and colleagues were interested in how different patterns of remaining versus dropping out of buprenorphine treatment across an entire year were related to two important health care outcomes: hospitalization and emergency room visits.

HOW WAS THIS STUDY CONDUCTED?

This study analyzed Pennsylvania Medicaid claims of 10,945 buprenorphine prescriptions from 2007 to 2012. In each case, the authors analyzed the data 12 months after this initial (sometimes called “index”) buprenorphine prescription.

READ MORE ON STUDY METHODS

They used a sophisticated analysis to establish six buprenorphine (Suboxone) prescription patterns over the course of the year:

 

1. Discontinued within 3 months of the original prescription (25%)
2. Discontinued 3-5 months after the original prescription (19%)
3. Discontinued 5-8 months after the original prescription (12%)
4. Discontinued more than 8 months after the original prescription (13%)
5. Discontinued but then refilled at a later time within the 12-month observation period (10%)
6. Refilled persistently throughout the 12-month observation period (21%)

 

To try and obtain a sample prescribed buprenorphine (Suboxone) just as a maintenance treatment medication for opioid use disorder, the authors excluded those with just one prescription – as this could have been for detoxification – and those with injection or transdermal (skin patch) formulations – as these are most often prescribed for pain management. Patients could not have had a buprenorphine prescription in the 6 months prior to the initial prescription used in this study. It is worth noting that one-third had a methadone prescription in the 6 months before the initial buprenorphine prescription used in the study. Consequently, these individuals had already experienced medication-assisted treatment, and with a full agonist (methadone) instead of the partial opioid agonist, buprenorphine, examined in this study.

Study authors compared five of the groups to the group who discontinued 3-5 months after the initial buprenorphine (Suboxone) prescription regarding their risk for being hospitalized (for any reason) and for being admitted to the emergency department across the entire 12 months. They controlled statistically for many demographic, social, and clinical factors that could influence these two primary outcomes. This statistical control was done to isolate the effect of these six different buprenorphine prescription patterns on the outcomes. The study sample was 18-64 years old (33 on average), 58% Female and 89% White. Most (85%) received buprenorphine from their primary care doctors.

Two Key Points:

 

1. First, 85% of the sample was covered by a buprenorphine (Suboxone) prescription in the first month after their initial prescription. However, the proportion covered by buprenorphine prescription dropped to 22% by the final month of analysis (month 12).
2. Second, those who discontinued at any point (versus those who refilled ongoing) were clinically more severe from the start, having greater likelihood of co-occurring alcohol use disorder, psychotic disorder, and use of clinical services more generally.

WHAT DID THIS STUDY FIND?

Before controlling statistically for demographic, social, and clinical factors, those who refilled persistently had:

• slightly lower rates of hospitalization (12% vs. 14-18% across the discontinuation groups)
• slightly lower rates of emergency department visits (31% vs. 35-44% across the discontinuation groups)

After controlling statistically for demographic, social, and clinical factors, those who refilled persistently had:

• 18% lower risk of hospitalization
• 14% lower risk of emergency department visits compared to those who discontinued 3-5 months after their initial prescription

As might be expected, overall, most of the hospitalizations were related to substance use or mental health disorders (76%).

Those who discontinued and restarted had 24% greater risk of an emergency department visit than those who discontinued during months 3-5.

WHY IS THIS STUDY IMPORTANT

For individuals who are prescribed Suboxone, this research highlights the importance of taking the medication on a consistent basis over the 1st year.

For those who restarted their medication after discontinuing, their greater “risk” of having visited the emergency department is probably best understood in the opposite direction. That is, they were likely restarted on buprenorphine after having visited the emergency room.

Also important was that rates of drop-out were much higher (69% of those initially prescribed the mediation) in this study than had been reported in previous studies. One possibility as to why is that engaging with a buprenorphine specialty program (i.e., that caters specifically to individuals receiving buprenorphine for opioid use disorder) provides services that help facilitate ongoing adherence to buprenorphine relative to a primary care physician. In this study, however, primary care physicians prescribed the medication for 85% of the sample in this study. Another possibility, is simply that individuals who engage with specialty programs are more motivated for treatment.

LIMITATIONS

1. While this large population based study had many strengths, it did not allow authors to determine actual rates of adherence to the medication. The data only allowed them to analyze whether or not a prescription was filled.
2. Also, these data were analyzed from a single state, and a single health care system/plan. We cannot be sure the results generalize to another state and to insurance apart from Medicaid. Perhaps most importantly, despite the authors best efforts to control statistically for other factors that might explain the worse outcomes for individuals who discontinued buprenorphine (Suboxone), this was an observational study design and there could have been influential factors for which the researchers could not account.
3. We also cannot be sure that the discontinuation caused the worse outcomes – just that they were related. Prior evidence and the statistical control, however, make it more likely that consistent adherence to buprenorphine versus discontinuation was responsible for lower rates of hospitalizations and emergency department visits.
4. Although the study authors also conducted analyses with several different kinds of outcome variables (e.g., only examining substance use and mental health related hospitalizations rather than any type of hospitalization), they reported that results were essentially unchanged and thus were not included in the article.
5. In this study, the timing of events (whether discontinuation came before or after the hospitalization/ emergency department visit) was not analyzed. So whether one caused the other cannot be determined.

NEXT STEPS

This timely and well done study should be replicated in other states and in samples of individuals with other health care plans. Also, studies of buprenorphine (Suboxone) outcomes for similar groups of individuals receiving treatment in specialty programs versus primary care physicians may be worthwhile.

BOTTOM LINE

CITATIONS

Lo‐Ciganic, W. H., Gellad, W. F., Gordon, A. J., Cochran, G., Zemaitis, M. A., Cathers, T., … & Donohue, J. M. (2016). Association between Trajectories of Buprenorphine Treatment and Emergency Department and In‐patient Utilization. Addiction.