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J Addict Med. 2016 Nov/Dec;10(6):418-428.

The Effect of Substance Use Disorders on the Association Between Guideline-concordant Long-term Opioid Therapy and All-cause Mortality.

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Yale School of Public Health (JRG, ACJ, DAF), Yale University, New Haven; VA Connecticut Healthcare System (JRG, JLG, WCB, KG, RDK, ACJ), West Haven; Yale Center for Medical Informatics (JRG, ACJ), Yale School of Medicine; Center for Interdisciplinary Research on AIDS (JRG, EJE, DAF), Yale School of Public Health, Yale University, New Haven, CT; Department of Psychiatry (JLG, RDK); Department of Internal Medicine (WCB, EJE, ACJ, DAF), Yale School of Medicine, Yale University, New Haven, CT; Institute for Health, Health Care Policy (SC), and Aging Research, Rutgers University, New Brunswick, NJ; Division of Infectious Diseases (DR), Emory University School of Medicine, Atlanta, GA; Atlanta VA Medical Center (DR), Decatur, GA; and VA Pittsburgh Healthcare System (MS), Pittsburgh, PA.



Patients with substance use disorders (SUDs) prescribed long-term opioid therapy (LtOT) are at risk for overdose and mortality. Prior research has shown that receipt of LtOT in accordance with clinical practice guidelines has the potential to mitigate these outcomes. Our objective was to determine whether the presence of a SUD modifies the association between guideline-concordant care and 1-year all-cause mortality among patients receiving LtOT for pain.


Among HIV+ and HIV- patients initiating LtOT (≥90 days opioids) between 2000 and 2010 as part of the Veterans Aging Cohort Study, we used time-updated Cox regression and propensity-score matching to examine-stratified by SUD status-the association between 1-year all-cause mortality and 3 quality indicators derived from national opioid-prescribing guidelines. Specifically, we examined whether patients received psychotherapeutic cointerventions (≥2 outpatient mental health visits), benzodiazepine coprescriptions (≥7 days), and SUD treatment (≥1 inpatient day or outpatient visit). These indicators were among those found in a previous study to have a strong association with mortality.


Among 17,044 patients initiating LtOT, there were 1048 (6.1%) deaths during 1 year of follow-up. Receipt of psychotherapeutic cointerventions was associated with lower mortality in the overall sample and was more protective in patients with SUDs (adjusted hazard ratio [AHR] 0.43, 95% confidence interval [CI] 0.33-0.56 vs AHR 0.65, 95% CI 0.53-0.81; P for interaction = 0.002). Benzodiazepine coprescribing was associated with higher mortality in the overall sample (AHR 1.41, 95% CI 1.22-1.63), but we found no interaction by SUD status (P for interaction = 0.11). Among patients with SUDs, receipt of SUD treatment was associated with lower mortality (AHR 0.43, 95% CI 0.33-0.57).


For clinicians prescribing LtOT to patients with untreated SUDs, engaging patients with psychotherapeutic and SUD treatment services may reduce mortality. Clinicians should also avoid, when possible, prescribing opioids with benzodiazepines.

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