The Association Between Receipt of Guideline-Concordant Long-Term Opioid Therapy and All-Cause Mortality

Abstract

PURPOSE:For patients receiving long-term opioid therapy (LtOT), the impact of guideline-concordant care on important clinical outcomes-notably mortality-is largely unknown, even among patients with a high comorbidity and mortality burden (e.g., HIV-infected patients). Our objective was to determine the association between receipt of guideline-concordant LtOT and 1-year all-cause mortality. METHODS: Among HIV-infected and uninfected patients initiating LtOT between 2000 and 2010 through the Department of Veterans Affairs, we used Cox regression with time-updated covariates and propensity-score matched analyses to examine the association between receipt of guideline-concordant care and 1-year all-cause mortality. RESULTS: Of 17,044 patients initiating LtOT between 2000 and 2010, 1048 patients (6%) died during 1 year of follow-up. Patients receiving psychotherapeutic cointerventions (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.51-0.75; P < 0.001) or physical rehabilitative therapies (HR 0.81; 95% CI 0.67-0.98; P = 0.03) had a decreased risk of all-cause mortality compared to patients not receiving these services, whereas patients prescribed benzodiazepines concurrent with opioids had a higher risk of mortality (HR 1.39; 95% CI 1.12-1.66; P < 0.001). Among patients with a current substance use disorder (SUD), those receiving SUD treatment had a lower risk of mortality than untreated patients (HR 0.47; 95% CI 0.32-0.68; P = < 0.001). No association was found between allcause mortality and primary care visits (HR 1.12; 95% CI 0.90-1.26; P = 0.32) or urine drug testing (HR 0.96; 95% CI 0.78-1.17; P = 0.67). CONCLUSIONS: Providers should use caution in initiating LtOT in conjunction with benzodiazepines and untreated SUDs. Patients receiving LtOT may benefit from multi-modal treatment that addresses chronic pain and its associated comorbidities across multiple disciplines.

The effect of substance use disorders on the association between guideline-concordant long-term opioid therapy and all-cause mortality

“…Because of the varied risks associated with opioid exposure Saunders et al, 2010;Solomon et al, 2010;Roy et al, 2011;Li et al, 2013;Veldhuizen & Callaghan, 2014) and the inherent challenges in accurately determining underlying cause of death, particularly for overdose deaths (Myers & Farquhar, 1998;Betz et al, 2008;Goldberger et al, 2013;Warner et al, 2013;Huguet et al, 2014;Slavova et al, 2015), we chose as our primary outcome allcause mortality. We found that patients who received psychotherapeutic co-interventions (i.e., mental health services) had lower mortality, while those receiving benzodiazepine concurrent with opioids had higher mortality (Gaither et al, 2016). Notably, we found that patients with an untreated substance use disorder had a mortality rate more than twice that of those who were engaged in treatment for this disorder (Gaither et al, 2016).…”

“…We found that patients who received psychotherapeutic co-interventions (i.e., mental health services) had lower mortality, while those receiving benzodiazepine concurrent with opioids had higher mortality (Gaither et al, 2016). Notably, we found that patients with an untreated substance use disorder had a mortality rate more than twice that of those who were engaged in treatment for this disorder (Gaither et al, 2016). It was this finding that prompted the current study, in which we sought to better understand how the presence of a substance use disorder moderated the outcome of all-cause mortality for the remaining indicators (i.e., psychotherapeutic co-interventions and benzodiazepine coprescribing).…”

“…Over the past two decades, patients and clinicians have increasingly relied on opioid analgesics to manage chronic non-cancer pain-millions of Americans now receive opioids long term, and are exposed to opioids for months and, frequently, years (Caudill-Slosberg et al, 2004;Korff et al, 2008;Sullivan et al, 2008;Braden et al, 2009;Martin et al, 2011;Volkow et al, 2011;Önen et al, 2012;Edelman et al, 2013;Gaither et al, 2014;Gaither et al, 2016). Although there are anecdotal reports of patients benefitting from extended opioid use (≥ 90 days), the safety and efficacy of long-term opioid therapy (LtOT) is not supported by strong scientific evidence (Korff et al, 2008;Rosenblum et al, 2008;Manchikanti et al, 2011;Von Korff et al, 2011;Chou et al, 2015).…”

“…In a previous study, we sought to better understand what role guideline-concordant LtOT plays in protecting patients from opioid-related harms (Gaither et al, 2016). Because of the varied risks associated with opioid exposure Saunders et al, 2010;Solomon et al, 2010;Roy et al, 2011;Li et al, 2013;Veldhuizen & Callaghan, 2014) and the inherent challenges in accurately determining underlying cause of death, particularly for overdose deaths (Myers & Farquhar, 1998;Betz et al, 2008;Goldberger et al, 2013;Warner et al, 2013;Huguet et al, 2014;Slavova et al, 2015), we chose as our primary outcome allcause mortality.…”

Capsule Commentary on Gaither et al., the Association Between Receipt of Guideline-Concordant Long-Term Opioid Therapy and All-Cause Mortality

“…T he article by Gaither et al 1 in this issue of JGIM is an important study. First, and most importantly, it properly concludes that initiating long-acting opioids in patients at increased risk for an overdose event or other serious harms related to co-prescription of benzodiazepines or in those with untreated substance use disorder is not a good idea.…”