Multimodal Care Reduces All-Cause Mortality in Opioid Users

Diana Swift

February 29, 2016

Better-quality care with multifaceted interventions may reduce the all-cause mortality risk for patients receiving long-term opioid therapy, according to an observational study published online February 3 in the Journal of General Internal Medicine.

Julie Gaither, PhD, MPH, RN, a postdoctoral research fellow at Yale University in New Haven, Connecticut, and colleagues found that chronic opioid users who received recommended psychiatric and other health services were about 40% less likely to die within the first 6 months of treatment initiation compared with similar patients who did not.

"Overall, our study suggests that patients who received care more in line with the standard recommended by leading medical societies have a reduced risk of experiencing serious outcomes from these narcotics," Dr Gaither commented to Medscape Medical News. "And patients who had an active alcohol or drug use disorder when starting opioids were twice as likely to die during this period if they were not receiving treatment for their addiction."

The researchers analyzed Veterans Affairs records from 17,044 eligible patients (mean age, 52 years; 98% male; 47% white) who started on long-term (≥90 days) opioid therapy for chronic noncancer pain between 2000 and 2010. In addition to pain, the cohort had a high burden of psychiatric and medical comorbidity, including HIV infection.

After 12 months, 1048 (6%) of patients had died, but guideline-concordant care, including mental health or substance abuse treatment and physical rehabilitation, was associated with a lower risk for death. With psychotherapeutic cointerventions, the hazard ratio was 0.57 (95% confidence interval [CI] 0.49 - 0.66; P < .001), and for rehabilitative therapies it was 0.60 (95% CI, 0.52 - 0.70; P < .001).

The effect was still significant when the researchers restricted their analysis to propensity-matched groups. Specifically, psychotherapeutic interventions were associated with a 38% reduction in mortality risk (HR, 0.62; 95% CI, 0.51 - .75; P < .001), and rehabilitative therapies were associated with a 19% reduction (HR, 0.81; 95% CI, 0.67 - 0.98; P < .03).

In contrast, those patients taking concurrent prescriptions for benzodiazepine sedatives (21%) were more than 1.5 times as likely to die as patients who were not taking them (HR, 1.39; 95% CI, 1.12 - 1.66; P < .001). Again, the effect remained significant among propensity-matched patients (HR, 1.39; 95% CI, 1.12 - 1.66; P < .001). The authors urged providers to exercise caution in such coprescribing.

Among patients with an active substance use disorder (19.5%), receiving treatment specific to this disorder was associated with reduced mortality (HR, 0.47; 95% CI, 0.32 - 0.68; P < .001) compared with patients with a substance use disorder who did not receive additional care. "Clinical practice guidelines state that opioids should never be initiated in patients with an untreated substance use disorder," Dr Gaither commented.

In contrast, primary care visits and urine drug tests had no significant effect on risk (HR, 1.12 [95% CI, 0.90 - 1.26; P = .32] and 0.96 [95% CI, 0.78 - 1.17; P = .67], respectively), confirming earlier research.

"This observational study — the first to examine the association between guideline-concordant [long-term opioid therapy] and mortality — lends support to current guidelines that promote a multidisciplinary approach to pain management, as well as to recommendations that caution against initiating [long-term opioid therapy] in conjunction with sedatives and untreated [substance use disorders]," the authors write.

They note that they opted to study all-cause mortality rather than overdose-related mortality because opioids act on a variety of systems and have a variety of adverse effects, including cardiovascular and gastrointestinal adverse effects. In addition, studying all-cause mortality eliminates the possibility of misclassifying the cause of death.

In an accompanying commentary published online February 16, also in the Journal of General Internal Medicine, Gary M. Franklin, MD, MPH, a research professor in the Department of Environmental and Occupational Health Sciences, the Department of Neurology, and the Department of Health Services at the University of Washington, Seattle, called the study important and lauded its conclusion that prescribing long-term opioids in high-risk patients should be avoided.

Dr Franklin also highlighted the study's finding that multidisciplinary care for chronic pain reduced all-cause mortality. Noting the absence of clear efficacy evidence for chronic opioid therapy in nonspecific pain disorders such as fibromyalgia and headache, he writes, "This makes the use of alternatives all that more attractive, considering that the evidence for dose-related serious harm is much stronger than the evidence of longer-term effectiveness."

This research was supported by grants from the National Institute on Drug Abuse, the National Institute on Alcohol Abuse and Alcoholism, the National Institute of Mental Health, the VA Health Services Research and Development Center of Innovation, and the Agency for Healthcare Research and Quality. One coauthor reported receiving an honorarium from Pinney Associates for advisory board services. The other authors and the commentator have disclosed no relevant financial relationships.

J Gen Intern Med. Published online February 4 and 16, 2016. Article abstract, Commentary extract

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