Clinical guidelines suggest opioid use disorder medications should continue for at least 6 months to provide benefit, but it is unclear what the optimal treatment duration may be. This study examined how length of opioid use disorder medication treatment was associated with risk for mortality among a sample of veterans.
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Opioid use disorder remains a significant public health concern: an estimated 80,000 people a year die from opioid overdoses. In addition, opioid use disorder increases the risk of death from other causes, including infectious diseases like Hepatitis and HIV. Medications for opioid use disorder improve quality of life and reduce risk of premature death, but optimal duration of treatment remains unclear. Clinical guidelines specify that patients should undergo treatment for at least 6 months, and evidence suggests that extending treatment beyond 1 year is associated with reduced mortality. However, it is unknown if prolonging treatment further confers additional reductions in risk of premature death. This study examined whether remaining on medication treatment for up to 6 years was associated with lower all-cause mortality.
This was a retrospective cohort study of 32,348 adults with opioid use disorder to determine how duration of medication (i.e., prescription of buprenorphine, methadone, or naltrexone) was associated with all-cause mortality risk. Data were from electronic health records of US veterans diagnosed with an opioid use disorder who initiated treatment via the Veteran’s Health Administration between October 1, 2010, and September 29, 2020. Opioid use disorder was identified using International Classification of Diseases 9 and 10 codes (specifically opioid use, dependence, or abuse). Duration of treatment was measured via the time between initial medication for opioid use disorder prescription and discontinuation of treatment (i.e., a gap of more than 28 days between last covered day from a previous prescription and the next documented receipt of any medication). The primary outcome of this research was all-cause mortality which was determined via the Veteran’s Health Administration Mortality Data Repository.
Results of these analyses are likely not generalizable due to the limitations of the data. First, the sample was comprised exclusively of veterans, and most patients were White (>66%) middle-aged (mean age>49) men (>92%). In addition, since patients received treatment via the Veteran’s Health Administration, they likely did not encounter common barriers to care including lack of health insurance and cost of treatment.
The study found that continuing opioid use disorder treatment duration past 1 year was associated with reduced risk of all-cause mortality. Patients who maintained medication prescriptions for at least 1 year were significantly less likely to die prematurely than those who maintained treatment for 6 months. Compared with 6 months of treatment, longer treatment durations were associated with progressively better predicted 6-year survival through about 4 to 5 years, after which gains were no longer significant.
Additional analyses were conducted to determine if regimen changes impacted study results. Separate statistical tests were run excluding patients who restarted treatment after discontinuation and patients who switched medication type. Results showed that even when these patients were removed from the analyses, the same patterns emerged. This suggests that longer treatment duration may reduce risk of premature death regardless of whether patients restart or change treatment.
This study suggests that extending opioid use disorder treatment (potentially up to 4 years or more) may improve survival among patients. Patients retained in treatment longer had better predicted 6-year survival, with gains continuing through about 4 to 5 years. Study results are promising but should be interpreted with caution. The study aggregated all types of opioid use disorder medications into one variable – i.e., though agonists buprenorphine/naloxone and methadone were the most common medications by far. Also, it is unclear why the benefits did not continue through to 6 years. It is possible, as authors suggest, that too few individuals continued to take medication for this long, rendering accurate predictions more difficult to make.
Results may not generalize given the specificity of the sample (i.e., US veterans who were majority White middle-aged men). In addition, while invaluable for epidemiological research, electronic health records analyses are often limited due to data issues, including diagnostic codes being imperfect measures of health behaviors, and missing data. Furthermore, it is beyond the scope of such data to determine how other factors may have impacted treatment adherence and mortality (e.g., health literacy and medication knowledge). Regardless of these limitations, the present study suggests that opioid use disorder treatment outcomes may improve when medications are maintained for several years, potentially 4 years or more—well beyond current clinical guidelines. While this study focused on all-cause mortality, other long–term studies suggest that agonist medications offer benefit in terms of reduced opioid use for many years.
Patients who remain on medications for opioid use disorder for at least 4 years may have better survival than those treated for only 6 months. Further research is needed to corroborate these findings and determine if current clinical guidelines should be revised.
Hayes, C. J., Raciborski, R. A., Acharya, M., Noor, N. B., Nunes, E. V., & Winhusen, T. J. (2026). Evaluating the optimal duration of medication treatment for opioid use disorder. Addiction, 121(4), 922-933. doi: 10.1111/add.70211.
l
Opioid use disorder remains a significant public health concern: an estimated 80,000 people a year die from opioid overdoses. In addition, opioid use disorder increases the risk of death from other causes, including infectious diseases like Hepatitis and HIV. Medications for opioid use disorder improve quality of life and reduce risk of premature death, but optimal duration of treatment remains unclear. Clinical guidelines specify that patients should undergo treatment for at least 6 months, and evidence suggests that extending treatment beyond 1 year is associated with reduced mortality. However, it is unknown if prolonging treatment further confers additional reductions in risk of premature death. This study examined whether remaining on medication treatment for up to 6 years was associated with lower all-cause mortality.
This was a retrospective cohort study of 32,348 adults with opioid use disorder to determine how duration of medication (i.e., prescription of buprenorphine, methadone, or naltrexone) was associated with all-cause mortality risk. Data were from electronic health records of US veterans diagnosed with an opioid use disorder who initiated treatment via the Veteran’s Health Administration between October 1, 2010, and September 29, 2020. Opioid use disorder was identified using International Classification of Diseases 9 and 10 codes (specifically opioid use, dependence, or abuse). Duration of treatment was measured via the time between initial medication for opioid use disorder prescription and discontinuation of treatment (i.e., a gap of more than 28 days between last covered day from a previous prescription and the next documented receipt of any medication). The primary outcome of this research was all-cause mortality which was determined via the Veteran’s Health Administration Mortality Data Repository.
Results of these analyses are likely not generalizable due to the limitations of the data. First, the sample was comprised exclusively of veterans, and most patients were White (>66%) middle-aged (mean age>49) men (>92%). In addition, since patients received treatment via the Veteran’s Health Administration, they likely did not encounter common barriers to care including lack of health insurance and cost of treatment.
The study found that continuing opioid use disorder treatment duration past 1 year was associated with reduced risk of all-cause mortality. Patients who maintained medication prescriptions for at least 1 year were significantly less likely to die prematurely than those who maintained treatment for 6 months. Compared with 6 months of treatment, longer treatment durations were associated with progressively better predicted 6-year survival through about 4 to 5 years, after which gains were no longer significant.
Additional analyses were conducted to determine if regimen changes impacted study results. Separate statistical tests were run excluding patients who restarted treatment after discontinuation and patients who switched medication type. Results showed that even when these patients were removed from the analyses, the same patterns emerged. This suggests that longer treatment duration may reduce risk of premature death regardless of whether patients restart or change treatment.
This study suggests that extending opioid use disorder treatment (potentially up to 4 years or more) may improve survival among patients. Patients retained in treatment longer had better predicted 6-year survival, with gains continuing through about 4 to 5 years. Study results are promising but should be interpreted with caution. The study aggregated all types of opioid use disorder medications into one variable – i.e., though agonists buprenorphine/naloxone and methadone were the most common medications by far. Also, it is unclear why the benefits did not continue through to 6 years. It is possible, as authors suggest, that too few individuals continued to take medication for this long, rendering accurate predictions more difficult to make.
Results may not generalize given the specificity of the sample (i.e., US veterans who were majority White middle-aged men). In addition, while invaluable for epidemiological research, electronic health records analyses are often limited due to data issues, including diagnostic codes being imperfect measures of health behaviors, and missing data. Furthermore, it is beyond the scope of such data to determine how other factors may have impacted treatment adherence and mortality (e.g., health literacy and medication knowledge). Regardless of these limitations, the present study suggests that opioid use disorder treatment outcomes may improve when medications are maintained for several years, potentially 4 years or more—well beyond current clinical guidelines. While this study focused on all-cause mortality, other long–term studies suggest that agonist medications offer benefit in terms of reduced opioid use for many years.
Patients who remain on medications for opioid use disorder for at least 4 years may have better survival than those treated for only 6 months. Further research is needed to corroborate these findings and determine if current clinical guidelines should be revised.
Hayes, C. J., Raciborski, R. A., Acharya, M., Noor, N. B., Nunes, E. V., & Winhusen, T. J. (2026). Evaluating the optimal duration of medication treatment for opioid use disorder. Addiction, 121(4), 922-933. doi: 10.1111/add.70211.
l
Opioid use disorder remains a significant public health concern: an estimated 80,000 people a year die from opioid overdoses. In addition, opioid use disorder increases the risk of death from other causes, including infectious diseases like Hepatitis and HIV. Medications for opioid use disorder improve quality of life and reduce risk of premature death, but optimal duration of treatment remains unclear. Clinical guidelines specify that patients should undergo treatment for at least 6 months, and evidence suggests that extending treatment beyond 1 year is associated with reduced mortality. However, it is unknown if prolonging treatment further confers additional reductions in risk of premature death. This study examined whether remaining on medication treatment for up to 6 years was associated with lower all-cause mortality.
This was a retrospective cohort study of 32,348 adults with opioid use disorder to determine how duration of medication (i.e., prescription of buprenorphine, methadone, or naltrexone) was associated with all-cause mortality risk. Data were from electronic health records of US veterans diagnosed with an opioid use disorder who initiated treatment via the Veteran’s Health Administration between October 1, 2010, and September 29, 2020. Opioid use disorder was identified using International Classification of Diseases 9 and 10 codes (specifically opioid use, dependence, or abuse). Duration of treatment was measured via the time between initial medication for opioid use disorder prescription and discontinuation of treatment (i.e., a gap of more than 28 days between last covered day from a previous prescription and the next documented receipt of any medication). The primary outcome of this research was all-cause mortality which was determined via the Veteran’s Health Administration Mortality Data Repository.
Results of these analyses are likely not generalizable due to the limitations of the data. First, the sample was comprised exclusively of veterans, and most patients were White (>66%) middle-aged (mean age>49) men (>92%). In addition, since patients received treatment via the Veteran’s Health Administration, they likely did not encounter common barriers to care including lack of health insurance and cost of treatment.
The study found that continuing opioid use disorder treatment duration past 1 year was associated with reduced risk of all-cause mortality. Patients who maintained medication prescriptions for at least 1 year were significantly less likely to die prematurely than those who maintained treatment for 6 months. Compared with 6 months of treatment, longer treatment durations were associated with progressively better predicted 6-year survival through about 4 to 5 years, after which gains were no longer significant.
Additional analyses were conducted to determine if regimen changes impacted study results. Separate statistical tests were run excluding patients who restarted treatment after discontinuation and patients who switched medication type. Results showed that even when these patients were removed from the analyses, the same patterns emerged. This suggests that longer treatment duration may reduce risk of premature death regardless of whether patients restart or change treatment.
This study suggests that extending opioid use disorder treatment (potentially up to 4 years or more) may improve survival among patients. Patients retained in treatment longer had better predicted 6-year survival, with gains continuing through about 4 to 5 years. Study results are promising but should be interpreted with caution. The study aggregated all types of opioid use disorder medications into one variable – i.e., though agonists buprenorphine/naloxone and methadone were the most common medications by far. Also, it is unclear why the benefits did not continue through to 6 years. It is possible, as authors suggest, that too few individuals continued to take medication for this long, rendering accurate predictions more difficult to make.
Results may not generalize given the specificity of the sample (i.e., US veterans who were majority White middle-aged men). In addition, while invaluable for epidemiological research, electronic health records analyses are often limited due to data issues, including diagnostic codes being imperfect measures of health behaviors, and missing data. Furthermore, it is beyond the scope of such data to determine how other factors may have impacted treatment adherence and mortality (e.g., health literacy and medication knowledge). Regardless of these limitations, the present study suggests that opioid use disorder treatment outcomes may improve when medications are maintained for several years, potentially 4 years or more—well beyond current clinical guidelines. While this study focused on all-cause mortality, other long–term studies suggest that agonist medications offer benefit in terms of reduced opioid use for many years.
Patients who remain on medications for opioid use disorder for at least 4 years may have better survival than those treated for only 6 months. Further research is needed to corroborate these findings and determine if current clinical guidelines should be revised.
Hayes, C. J., Raciborski, R. A., Acharya, M., Noor, N. B., Nunes, E. V., & Winhusen, T. J. (2026). Evaluating the optimal duration of medication treatment for opioid use disorder. Addiction, 121(4), 922-933. doi: 10.1111/add.70211.
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