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Health Services Research & Development

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Improving the Safety of Opioid Treatment

July 2017


Over the past two decades a dramatic rise in the sale of prescription opioids in the United States has coincided with the rise of opioid overdose deaths and other opioid-related adverse outcomes.1 In addition, during the last 15 years more than 165,000 people in this country have died from overdoses related to prescription opioids, and millions more have suffered adverse consequences. So in 2013, VA launched the Opioid Safety Initiative (OSI), the first of several system-wide initiatives to address opioid overuse. As a result, by mid-2016 the number of Veterans dispensed an opioid each quarter had decreased by 172,000, or about 25%. In 2017, even fewer Veterans are receiving high doses of opioids or concomitant interacting medicines like benzodiazepines, and more Veterans are receiving non-opioid pain therapies, naloxone, and treatment for substance use disorders.2

Following are descriptions and findings from several specific research projects conducted by HSR&D and QUERI (Quality Enhancement Research Initiative) investigators on issues critical to improving the safety of opioid treatment.

Addressing the Opioid Epidemic: Lessons Learned from VA

This article describes VA's efforts to address the opioid epidemic, and lessons learned that can inform other healthcare systems planning comprehensive action to reduce the risks associated with opioid therapy. VA has employed four broad strategies to address the opioid epidemic: 1) Education, 2) Pain Management, 3) Risk Mitigation, and 4) Addiction Treatment. The educational initiatives include academic detailing, educational programming, and an informed consent requirement for VA patients who are prescribed chronic opioid therapy. As part of its efforts to improve pain management, VA issued a policy directive for stepped pain care, emphasizing interdisciplinary teamwork as a delivery model for pain management, and expanded access to non-opioid pain treatment. VA implemented several strategies to support and track risk mitigation activities for opioid therapy; for example, a Stratification Tool for Opioid Risk Mitigation (STORM) uses predictive modeling to estimate the risk of overdose or suicide-related event for each VA patient on opioids. VA also has an extensive system for addiction treatment through inpatient and outpatient care. In addition, VA has an extensive residential program for long-term addiction treatment that served nearly 15,000 Veterans in 2015. VA has made progress and important lessons have been learned. For example, the balance between appropriately treating pain and reducing the risks of opioid use requires careful attention. In some cases this means reducing the number of patients receiving opioids, but in other cases it means improving the safety of opioid use among those who require such medications. Also, in capturing regional and clinician-specific data, VA can identify both 'best practices' and outliers on which to focus its efforts. Although national policies addressing opioid use are important, local action has been the real driver of change.

Gellad W, Good C, and Shulkin D. Addressing the opioid epidemic in the United States: Lessons from the Department of Veterans Affairs. JAMA Internal Medicine. May 1, 2017;177(5):611-612.

Discontinuation of Long-Term Opioid Therapy among Veterans is Overwhelmingly Initiated by VA Clinicians

Patients with substance use disorder (SUD) are at increased risk of experiencing opioid-related adverse events. This HSR&D retrospective study compared reasons for discontinuation of long-term opioid therapy (LTOT) between Veterans with (n=300) and without SUD (n=300) receiving care within the VA healthcare system in the years following release of the 2009 and 2010 opioid clinical practice guidelines, which recommended discontinuation of opioid therapy under several circumstances (i.e., patient behaviors that heighten the risk of opioid overdose and death). Investigators reviewed patients' medical records to determine the reasons for LTOT discontinuation during 2012, as well as patient outcomes following discontinuation. For this study, LTOT was defined as having been prescribed opioid therapy for the entirety of 2011. Findings from this study and two related studies by HSR&D investigator Travis Lovejoy, PhD, MPH, show:

  • The majority of Veterans (85%) discontinued opioid use because their clinician stopped prescribing, rather than the patients deciding to stop.1

  • For patients whose clinicians initiated discontinuation, 75% were discontinued due to opioid-related aberrant behaviors (i.e., suspected substance abuse at 51% and aberrant urine drug test at 44%).1
  • Among patients discontinued by the opioid-prescribing clinician, 2.4% had a suicide attempt documented in the medical record in the year following discontinuation, rates commensurate with a VA mental health treatment-seeking population.2
  • For patients discontinued due to a urine drug test positive for alcohol, cannabis, other illicit, or non-prescribed controlled substances, 43% were referred for SUD treatment, and only 20% engaged in SUD treatment.3

Implications: Increasing rates of opioid discontinuation are likely to occur due to policies and programs that encourage close monitoring of Veterans on LTOT for opioid misuse behaviors. Integrating non-opioid pain therapies and SUD treatment into multiple settings such as primary care and specialty SUD care is one possible approach to enhance their care.

1. Lovejoy T, Morasco B, Demidenko M, et al. Reasons for discontinuation of long-term opioid therapy in patients with and without substance use disorders. Pain. March 2017;158(3):526-534.

2. Demidenko M, Dobscha S, Morasco B, et al. Suicidal ideation and suicidal self-directed violence following clinician-initiated prescription opioid discontinuation among long-term opioid users. General Hospital Psychiatry. July-August 2017;47:29-35.

3. Nugent S, Dobscha S, Morasco B, et al. Substance use disorder treatment following clinician-initiated discontinuation of long-term opioid therapy resulting from an aberrant urine drug test. Journal of General Internal Medicine. June 9, 2017; Epub ahead of print.

VA Opioid Safety Initiative Associated with Decreases in Potentially Risky Opioid Prescriptions

In 2013, VA leadership developed and implemented the Opioid Safety Initiative (OSI) to promote safer opioid-related prescribing for Veterans in the VA healthcare system. Key components of the OSI include a dashboard tool that uses VA electronic health record data to generate displays of real-time opioid-related prescribing – and identifies a clinical leader at each facility to implement the tool and promote safer prescribing. This retrospective QUERI study examined changes associated with OSI implementation among all adult VA patients who filled outpatient opioid prescriptions from October 2012 through September 2014 in any of 141 VA facilities. Investigators focused on total daily opioid dosages at thresholds of >100 morphine-equivalent milligrams (mEq) and >200 mEq because these have been associated with increased risk of unintentional overdose – and are displayed on the OSI dashboard tool. The numbers of patients receiving a benzodiazepine (i.e., alprazolam, clonazepam, and diazepam) concurrently with an opioid (i.e., codeine, morphine, and oxycodone) were also analyzed. Findings show:

  • During the study period there was a decrease in the number of Veterans receiving risky opioid regimens. In October 2012, 55,722 Veterans received daily dosages of opioids >100 mEq, which decreased to 46,780 Veterans in September 2014, for an overall reduction of 16%. In October 2012, 19,952 Veterans received total daily dosages of opioids >200 mEq, which decreased to 15,121 patients by September 2014, for an overall reduction of 24%.
  • In October 2012, 112,907 Veterans received benzodiazepines concurrently with opioids, which decreased to 89,564 Veterans by September 2014, for an overall reduction of 21%.
  • Implementation of the OSI dashboard tool was associated with a significant decrease in all three outcomes (>100 mEq, >200 mEq and concurrent opioid/benzodiazepine prescribing).

Implications: The implementation of the OSI dashboard tool was associated with a significant decrease in risky opioid prescribing across the VA healthcare system, which highlights the possibility of system-wide approaches to address high-risk opioid prescribing.

Lin L, Bohnert A, Kerns R, et al. Impact of the opioid safety initiative on opioid-related prescribing in Veterans. Pain. May 2017;158(5):833-839.

Safety Risk for Veterans Receiving Overlapping Prescriptions from VA and Medicare Part D

Ensuring safe buprenorphine (used to treat opioid addiction) prescribing is especially challenging for VA, which treats a substantial number of Veterans with chronic pain and opioid use disorder, as well as an increasing number of patients who receive concurrent care in the private sector (i.e., Medicare Part D). This HSR&D study identified 1,790 Veterans dually enrolled in VA and Medicare Part D who filled a buprenorphine prescription in 2012, including 760 (43%) filling from VA and 1,091 (61%) from Medicare. Investigators then determined the proportion of Veterans that received any overlapping prescription for a non-buprenorphine opioid or benzodiazepine from a different system than their buprenorphine prescription (Part D buprenorphine recipients receiving overlapping opioids or benzodiazepines from VA and vice versa). Findings show:

  • Among Veterans who received their buprenorphine prescription from VA, 199 (26%) received an overlapping opioid prescription from Part D. Among those who received buprenorphine from Medicare, 208 (19%) also received an opioid prescription from VA.
  • Among VA and Part D buprenorphine recipients who had cross-system opioid overlap, 25% (49/199) and 35% (72/208), respectively, had >90 days of overlap.

Implications: Findings indicate a previously undocumented safety risk for Veterans dually enrolled in VA and Medicare who are receiving prescriptions for buprenorphine and over-lapping prescriptions for opioids and/or benzodiazepines. This is important as both VA and Medicare seek to expand buprenorphine treatment for substance use disorder, and as VA expands access to non-VA community care for Veterans.

Gellad W, Zhao X, Thorpe C, et al. Overlapping buprenorphine, opioid, and benzodiazepine prescriptions among Veterans dually enrolled in Department of Veterans Affairs and Medicare Part D. Substance Abuse. January – March 2017;38(1):22-25.

Veteran Smokers More Likely to Receive Opioid Prescription than Non-Smokers

Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND) Veterans smoke at twice the rate of similarly-aged US civilian adults (40% vs 19%). Cigarette smoking rates are higher among individuals with mental health diagnoses, such as anxiety, depression, PTSD, and substance use disorders, which also are highly prevalent among Veterans receiving VA healthcare. Further, clinically significant pain is reported by more than one-third of OEF/OIF/OND Veterans, and smoking status has been shown to be associated with pain in this cohort.1 This HSR&D study sought to determine if smoking status is associated with the receipt of opioids among OEF/OIF/OND Veterans – and to examine important covariates of smoking (i.e., current pain intensity, gender, and mental health diagnoses) and receipt of opioids. Using VA and DoD data, investigators identified 406,954 OEF/OIF/OND Veterans (including 50,988 women) who had at least one visit to a VA primary care clinic between 2001 and 2012, as well as available smoking status and pain intensity score data. Findings show:

  • Compared to non-smokers, OEF/OIF/OND Veterans who were current smokers were more likely to receive an opioid prescription, even after controlling for covariates including: pain intensity, age, gender, service-connection, substance use disorder, mood disorders, and anxiety disorders. Veterans who reported a higher current pain intensity and those with pain diagnoses also were more likely to receive an opioid prescription.
  • Among this young cohort of Veterans (mean age=30 years), more than one-third (34%) reported moderate to severe current pain intensity within +/-30 days of smoking status, with approximately 8% (n=32,994) receiving at least one opioid prescription.

Implications: Smoking status should be an essential consideration when evaluating OEF/OIF/OND Veterans with pain and opioid use. Clinical implications suggest targeting smoking cessation in the context of pain and opioid use, and offering non-pharmacologic therapies for treating chronic pain.

Bastian L, Driscoll M, Heapy A, et al. Cigarette smoking status and receipt of an opioid prescription among Veterans of recent wars. Pain Medicine. June 1, 2017;18(6):1089-97..

1. Volkman J, DeRycke E, Driscoll M, et al. Smoking status and pain intensity among OEF/OIF/OND Veterans. Pain Medicine 2015;16:1690-96.

Prescription Opioid Use among Patients with Recent History of Depression Increases Risk of Recurrence

Pain and depression are highly comorbid, and patients with depression are more likely to use opioids even when functioning is good. Moreover, a growing body of literature suggests that patients with chronic non-cancer pain who are prescribed opioids are more likely to develop depression. This study examined whether patients in depression remission who were prescribed opioids for non-cancer pain had an increased risk of depression recurrence, after controlling for covariates. Investigators analyzed two patient populations: 5,400 Veterans treated in the VA healthcare system, and 842 patients treated by Baylor Scott & White Health (BSWH) – a non-profit integrated healthcare system located in Texas. All study participants had been free of opioid use for at least two years, had a diagnosis of depression, and experienced depression remission during follow-up. The observation period for VA patients was 2002 through 2012, and for BSWH was 2003 through 2012. Findings show:

  • Prescription opioid use among patients with a recent history of depression increased the chance of depression recurrence, and this effect was independent of pain diagnoses and pain intensity scores.
  • Patients with remitted depression who were exposed to opioid analgesics at any point during the follow-up period were 77% to 117% more likely to experience a recurrence of depression than those who remained opioid free, after controlling for other factors.

Implications: Study findings highlight a particularly challenging situation faced by clinicians and patients with pain – and point to the need for careful consideration of depression in the assessment of benefit and risk of opioid use.1

Another study conducted by HSR&D investigator Jeffrey Scherrer, PhD, and colleagues found that the risk of developing treatment-resistent depression (TRD) for Veterans increased as time spent on opioid analgesics increased. In a cohort of 6,169 VA patients with depression at baseline, those who initiated and remained on an opioid for 31-90 days were 25% more likely,, and those who remained users for >90 days were 52% more likely to transition to TRD compared to patients who used for only 1-30 days.2

1. Scherrer J, Salas J, Copeland L, et al. Increased risk of depression recurrance after initiation of prescription opioids in non-cancer pain patients. The Journal of Pain. April 2016;17(4):473-482.

2. Scherrer J, Salas J, Sullivan M, et al. The influence of prescription opioid use duration and dose on development of treatment resistant depression. Preventive Medicine. October 2016;91:110-116.


1. Lin L, Bohnert A, Kerns R, et al. Impact of the Opioid Safety Initiative on opioid-related prescribing in Veterans. Pain. May 2017;158(5):833-839.

2. Gellad W, Good C, and Shulkin D. Addressing the opioid epidemic in the United States: Lessons from the Department of Veterans Affairs. JAMA Internal Medicine. May 1, 2017;177(5):611-612.

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