Here’s something most people in the field know: buprenorphine treatment lowers the risk of overdose and death in people with opioid use disorder (OUD).
And here’s what many don’t know: most patients don’t remain in buprenorphine treatment long enough to benefit from it. Six months is the shortest time endorsed by the National Quality Forum, but most patients—50% to 80%—stop taking buprenorphine after just a few weeks or months. Even the recommended six months of treatment is not long enough, an important new study shows. Patients still face a high risk of serious, potentially fatal problems when they do quit.
So, why do patients leave buprenorphine treatment so quickly?
And what length of buprenorphine treatment offers the best outcomes?
Answers to these questions, and others, are found in a recent article published online ahead of print in the American Journal of Psychiatry: “Acute care, prescription opioid use, and overdose following discontinuation of long-term buprenorphine treatment for opioid use disorder.” The investigators are from Columbia University Medical Center and Columbia’s Mailman School of Public Health, both in New York; and Rutgers University, in New Jersey.
Reasons Patients Quit Buprenorphine Therapy
Buprenorphine, the most widely used medication for OUD, is administered to about 700,000 people every year—a minority of the estimated 2 million to 5 million people who have OUD. Experts generally don’t put time limits on therapy to treat OUD, but –
- Insurance policies may restrict patients’ access to buprenorphine, or limit treatment to six-month intervals
- Patients often try to taper off treatment after early improvement; reasons include stigma, attitudinal factors (motivation, self-esteem), family pressure, and doctors’ lack of training
The result: patients stop taking buprenorphine much too soon.
The Study
This is the first study to look at data from patients who took buprenorphine continuously for at least six months, then discontinued treatment, and whose data were assessed during the six months after they stopped treatment. Other studies have assessed risks during treatment.
This was a retrospective study that tapped into the MarketScan multistate Medicaid claims database, a source that covers 12 million people each year. Study data are presented by three-month cohorts (patient groups), depending on treatment duration, shown in the table below.
Results
The analysis included 8,996 individuals on buprenorphine for a minimum of six months. Primary adverse outcomes were emergency department visits (all cause), inpatient hospitalizations (all cause), medically treated drug overdose (opioid and nonopioid), and receipt of full-agonist opioid prescriptions. (Because full-agonist opioids are generally contraindicated in OUD patients being treated with buprenorphine, such opioid prescriptions generally indicate relapse or poorly coordinated care.)
Adverse events were common in all study groups. More than one-fourth of patients had opioid prescription claims, and almost half had claims for one or more emergency department visits.
Overdoses: a special concern. The authors commented that medically treated overdoses occurred in about 5% of patients, across the board. So, overdose seems to remain a common event following discontinuation, regardless of the length of buprenorphine treatment. Another telling statistic: about two to three times as many people in the study groups had overdoses after discontinuation as are reported in the general population of people with OUD.
Six months: a high-risk period. The authors noted “a high-risk period for adverse events”—the six-month window after discontinuation. This was especially true for patients who also had a mental illness. The high risk existed no matter how long the patient had stayed in buprenorphine treatment, but was somewhat lower among those retained on medication for longer periods.
Outcomes over time. Outcomes for patients in the study did eventually improve somewhat, but not until 15 months of maintenance treatment with buprenorphine. Even then, substantial risks remained. Patients in the cohort with the longest treatment period,15 to 18 months, had the best clinical outcomes (see table below), although “rates of the primary adverse outcomes remained high,” the investigators commented.
Summary of Adverse Events (Table)
The table below summarizes findings on adverse events in the study group. To clarify: all patients remained in treatment for at least six months, but no longer than 18 months, then stopped taking buprenorphine. Investigators gathered the data on adverse events during the six months after treatment ended.
Thus, patients in the group in the first column on the left continued treatment for 6 to 9 months before stopping; data were analyzed during the six months that followed. Patients in the column on the far right remained in treatment for 15 to 18 months, then discontinued, and their data were analyzed during the next six months.
Incidence of Adverse Events
During the Six Months
After Buprenorphine Was Discontinued
| Reference Group 6–9 Months N=4,126 | 9–12 Months N=2,440 | 12–15 Months N=1,499 | 15–18 Months N=931 |
|---|---|---|---|
| Highest rates of adverse events occurred in this group,a although overdose was equivalent across all groups | Types of adverse events in this group were similar to those in the reference group | Findings for those in treatment for 12-15 months showed only lower rates of ED visits and opioid prescription use | The risk of three key adverse events was lower in this group than in the other cohorts,b but remained high |
aRates of adverse events were statistically significantly lower in all groups than they were in the reference group.
bThe difference in rates of adverse events between groups reached the highest level of statistical significance in the 15-18 Month group.
Key Findings
- Buprenorphine discontinuation is associated with serious risks, even after long-term (15 to 18 months) care episodes
- Rates of overdose after buprenorphine is discontinued are “approximately two to three times higher than those observed in a general sample of patients with opioid use disorder”
Recommendations
Ways to improve long-term retention, the authors noted, include directing “greater efforts at the clinical and systems levels,” with priority given to redesigning systems of care. Redesigning means emphasizing chronic disease management models under collaborative care teams. The teams should have “emergency response capabilities for reaching patients who discontinue medication or disengage from care,” by “leveraging public and private insurance benefit design, utilization management, and clinical policies.”
To improve patient outcomes, the authors suggested considering “structural interventions, such as placement of care coordinators, development and routine monitoring or quality measures, and capitated or enhanced provider reimbursement for extended buprenorphine treatment.”
The bottom line. The authors noted that in their study, “eventual treatment discontinuation was associated with high rates of potentially fatal adverse events in the ensuing months.” They added that the results of their investigation are consistent with those from a growing number of studies emphasizing the protective effects of long-term therapy in OUD—in sharp contrast to short-term therapy or brief detoxification. In a communication with Addiction Treatment Forum, the study’s lead author, Arthur Robin Williams, MD, MBE, commented: “Discontinuation of buprenorphine is a life-threatening event for many patients, and should be treated as such.”
Reference
Williams AR, Samples H, Crystal S, Olfson M. Acute care, prescription opioid use, and overdose following discontinuation of long-term buprenorphine treatment for opioid use disorder. AJP in Advance. 2019; doi: 10.1176/appi.ajp.2019.19060612
Additional Reading
Dennis ML, Foss MA, Scott CK. An eight-year perspective on the relationship between the duration of abstinence and other aspects of recovery. Eval Rev. 2007; 31:585-6122. doi: 10.1177/0193841X07307771
Sordo L, Barrio G, Bravo MJ, et al. Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. BMJ. 2017; 357:j1550. doi: https://doi.org/10.1136/bmj.j1550
Here’s something most people in the field know: buprenorphine treatment lowers the risk of overdose and death in people with opioid use disorder (OUD).
And here’s what many don’t know: most patients don’t remain in buprenorphine treatment long enough to benefit from it. Six months is the shortest time endorsed by the National Quality Forum, but most patients—50% to 80%—stop taking buprenorphine after just a few weeks or months. Even the recommended six months of treatment is not long enough, an important new study shows. Patients still face a high risk of serious, potentially fatal problems when they do quit.
So, why do patients leave buprenorphine treatment so quickly?
And what length of buprenorphine treatment offers the best outcomes?
Answers to these questions, and others, are found in a recent article published online ahead of print in the American Journal of Psychiatry: “Acute care, prescription opioid use, and overdose following discontinuation of long-term buprenorphine treatment for opioid use disorder.” The investigators are from Columbia University Medical Center and Columbia’s Mailman School of Public Health, both in New York; and Rutgers University, in New Jersey.
Reasons Patients Quit Buprenorphine Therapy
Buprenorphine, the most widely used medication for OUD, is administered to about 700,000 people every year—a minority of the estimated 2 million to 5 million people who have OUD. Experts generally don’t put time limits on therapy to treat OUD, but –
- Insurance policies may restrict patients’ access to buprenorphine, or limit treatment to six-month intervals
- Patients often try to taper off treatment after early improvement; reasons include stigma, attitudinal factors (motivation, self-esteem), family pressure, and doctors’ lack of training
The result: patients stop taking buprenorphine much too soon.
The Study
This is the first study to look at data from patients who took buprenorphine continuously for at least six months, then discontinued treatment, and whose data were assessed during the six months after they stopped treatment. Other studies have assessed risks during treatment.
This was a retrospective study that tapped into the MarketScan multistate Medicaid claims database, a source that covers 12 million people each year. Study data are presented by three-month cohorts (patient groups), depending on treatment duration, shown in the table below.
Results
The analysis included 8,996 individuals on buprenorphine for a minimum of six months. Primary adverse outcomes were emergency department visits (all cause), inpatient hospitalizations (all cause), medically treated drug overdose (opioid and nonopioid), and receipt of full-agonist opioid prescriptions. (Because full-agonist opioids are generally contraindicated in OUD patients being treated with buprenorphine, such opioid prescriptions generally indicate relapse or poorly coordinated care.)
Adverse events were common in all study groups. More than one-fourth of patients had opioid prescription claims, and almost half had claims for one or more emergency department visits.
Overdoses: a special concern. The authors commented that medically treated overdoses occurred in about 5% of patients, across the board. So, overdose seems to remain a common event following discontinuation, regardless of the length of buprenorphine treatment. Another telling statistic: about two to three times as many people in the study groups had overdoses after discontinuation as are reported in the general population of people with OUD.
Six months: a high-risk period. The authors noted “a high-risk period for adverse events”—the six-month window after discontinuation. This was especially true for patients who also had a mental illness. The high risk existed no matter how long the patient had stayed in buprenorphine treatment, but was somewhat lower among those retained on medication for longer periods.
Outcomes over time. Outcomes for patients in the study did eventually improve somewhat, but not until 15 months of maintenance treatment with buprenorphine. Even then, substantial risks remained. Patients in the cohort with the longest treatment period,15 to 18 months, had the best clinical outcomes (see table below), although “rates of the primary adverse outcomes remained high,” the investigators commented.
Summary of Adverse Events (Table)
The table below summarizes findings on adverse events in the study group. To clarify: all patients remained in treatment for at least six months, but no longer than 18 months, then stopped taking buprenorphine. Investigators gathered the data on adverse events during the six months after treatment ended.
Thus, patients in the group in the first column on the left continued treatment for 6 to 9 months before stopping; data were analyzed during the six months that followed. Patients in the column on the far right remained in treatment for 15 to 18 months, then discontinued, and their data were analyzed during the next six months.
Incidence of Adverse Events
During the Six Months
After Buprenorphine Was Discontinued
| Reference Group 6–9 Months N=4,126 | 9–12 Months N=2,440 | 12–15 Months N=1,499 | 15–18 Months N=931 |
|---|---|---|---|
| Highest rates of adverse events occurred in this group,a although overdose was equivalent across all groups | Types of adverse events in this group were similar to those in the reference group | Findings for those in treatment for 12-15 months showed only lower rates of ED visits and opioid prescription use | The risk of three key adverse events was lower in this group than in the other cohorts,b but remained high |
aRates of adverse events were statistically significantly lower in all groups than they were in the reference group.
bThe difference in rates of adverse events between groups reached the highest level of statistical significance in the 15-18 Month group.
Key Findings
- Buprenorphine discontinuation is associated with serious risks, even after long-term (15 to 18 months) care episodes
- Rates of overdose after buprenorphine is discontinued are “approximately two to three times higher than those observed in a general sample of patients with opioid use disorder”
Recommendations
Ways to improve long-term retention, the authors noted, include directing “greater efforts at the clinical and systems levels,” with priority given to redesigning systems of care. Redesigning means emphasizing chronic disease management models under collaborative care teams. The teams should have “emergency response capabilities for reaching patients who discontinue medication or disengage from care,” by “leveraging public and private insurance benefit design, utilization management, and clinical policies.”
To improve patient outcomes, the authors suggested considering “structural interventions, such as placement of care coordinators, development and routine monitoring or quality measures, and capitated or enhanced provider reimbursement for extended buprenorphine treatment.”
The bottom line. The authors noted that in their study, “eventual treatment discontinuation was associated with high rates of potentially fatal adverse events in the ensuing months.” They added that the results of their investigation are consistent with those from a growing number of studies emphasizing the protective effects of long-term therapy in OUD—in sharp contrast to short-term therapy or brief detoxification. In a communication with Addiction Treatment Forum, the study’s lead author, Arthur Robin Williams, MD, MBE, commented: “Discontinuation of buprenorphine is a life-threatening event for many patients, and should be treated as such.”
Reference
Williams AR, Samples H, Crystal S, Olfson M. Acute care, prescription opioid use, and overdose following discontinuation of long-term buprenorphine treatment for opioid use disorder. AJP in Advance. 2019; doi: 10.1176/appi.ajp.2019.19060612
Additional Reading
Dennis ML, Foss MA, Scott CK. An eight-year perspective on the relationship between the duration of abstinence and other aspects of recovery. Eval Rev. 2007; 31:585-6122. doi: 10.1177/0193841X07307771
Sordo L, Barrio G, Bravo MJ, et al. Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. BMJ. 2017; 357:j1550. doi: https://doi.org/10.1136/bmj.j1550