EXPANDING THE UNDERSTANDING OF RISKS ASSOCIATED WITH OPIOIDS AS WELL AS STRATEGIES TO REDUCE OPIOID OVERUSE

Mark Ilgen, PhD

VA Center for Clinical Management ResearchDepartment of Psychiatry, University of Michigan

Acknowledgements and Disclosures2

This work was supported by the Department of Veterans Affairs. Research - VA Quality Enhancement Research Initiative (RRP

13-251) Evaluation - VA Serious Mental Illness Treatment Research

and Evaluation Center (SMITREC) These are my opinions and do not necessary represent

those of VHA Collaborators

Amy Bohnert, PhD Allison Lin, MD Dara Ganoczy, MPH

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Overview Goal – utilize VHA data to inform an

understanding of risks associated with opioids as well as the potential impact of strategies to mitigate those risks.

Two studies (both based in VHA): An examination of the relationship

between opioids and suicide risk An evaluation of changes in risky opioid

prescribing before, during, and after the national roll-out of the opioid safety initiative (OSI)

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Pain and suicide-related outcomes

Several studies have documented: The elevated prevalence of suicidal thoughts

and behaviors in pain clinic patients (Fishbain, Clin J Pain, 1991)

The cross-sectional association between self-reported pain and suicidal ideation and non-fatal attempts (Breslau, Neurology, 1992; Ilgen et al., Gen Hosp Psych, 2008)

The longitudinal relationship between Self-reported pain severity and suicide

mortality (Ilgen et al., SLTB, 2010) Pain conditions and suicide mortality (Ilgen et

al., JAMA Psychiatry, 2013)

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Treating pain with opioids: A “lifeline” that could help reduce risk of suicide

LYNN R. WEBSTER, MD: President, American Academy of Pain Medicine

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Opioid Access and Suicide Prevention

Limiting Access to Means of Suicide Most studies looking at access to means—

whether guns, pills, carbon monoxide, bridges, or other suicide methods—have found that making these methods less available reduces suicide rates.

www.afsp.org/preventing-suicide

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Methods Case-cohort design For each of the two study years, a 5% random sample

of patients was drawn, irrespective of case status. Cases were all FY04-FY05 VHA patients who died by

suicide before the end of FY09. Both cases and controls were further restricted to all

individuals with a chronic pain condition who were treated with an opioid.

Individuals with indicators of palliative care consultations or hospice care in their VHA medical records were excluded (n=1926)

The sample size was 123,946.

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Methods Primary outcomes:

Suicide mortality was based on deaths classified by the International Classification of Diseases-10 (ICD-10) codes X60-X84 and Y87.0 in the NDI.

intentional overdose was identified by ICD-10 codes X60-X69.

Predictors: This study focused on maximum prescribed morphine-equivalent daily opioid dose. Morphine-equivalent doses were calculated for codeine, morphine, oxycodone, hydrocodone, oxymorphone, and hydromorphone using established methods. The present analyses did not examine synthetic opioids (which include buprenorphine) or methadone.

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Results: Cox Proportional Hazards Models of Risk of Death by Suicide

 Suicide, Any

MechanismIntentional Overdose

HR (95% CI) HR (95% CI)

Prescribed Daily Opioid Dose    

1 to < 20 mg/d 1.00 1.00

20 to < 50 mg/d 1.48 (1.25, 1.75) 1.59 (1.12, 2.27)

50 to < 100 mg/d 1.69 (1.33, 2.14) 1.74 (1.09, 2.76)

100+ mg/d 2.15 (1.64, 2.81) 2.09 (1.22, 3.56)

Adjusted for age, sex, race, Hispanic ethnicity, number of pain conditions, number of psychiatric conditions, Charlson comorbidity Index, and opioid schedule.

Note: All comparisons for opioids significant at p < 0.05 compared to 1 to < 20; comparison between 1300 to 2000 and less than 1300 for acetaminophen significant at p < 0.05

Examining acetaminophen for comparison……

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Bohnert, Valenstein, Bair, Ganoczy, McCarthy, Ilgen, Blow, JAMA. 2011.

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Conclusion: Opioids and suicide Limitations: Is an observational study

Patient: Is opioid dose a proxy for increased pain? Treatment: Is higher opioid dose a proxy for poor pain care?

No signal for potential protective effect of opioids on risk of suicide

Increases in opioid dose are associated with increased risk of suicide This association is not limited to intentional overdose

Chance that opioids impair judgment and could increase the likelihood of engaging in suicidal behaviors

The magnitude of the observed association was much lower than what has been described for unintentional overdose.

GIVEN THE ASSOCIATION BETWEEN OPIOIDS AND ADVERSE OUTCOMES… WHAT CAN BE DONE ABOUT IT

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A national approach to address high-risk opioid prescribing The Opioid Safety Initiative (OSI) was designed to

increase safe opioid prescribing. The Under Secretary for Health charged a task

force to develop and deploy an opioid surveillance system that provides detailed and specific information about opioid prescribing to all VHA facilities.

This resulted in a Business Intelligence (BI) tool to provide data on opioid prescribing to all facilities. Goals, to reduce

Use of very high dosages of opioids Co-use of opioids and sedatives

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Evaluation goals for this project To examine recent trends in opioid

prescribing in VHA and whether any notable changes coincided with the national roll-out of the Opioid Safety Initiative (OSI)

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Methods Obtain facility-level data on opioid and sedative

prescribing during the year prior to, and the year following, the national roll-out of the OSI

Conduct interrupted time series analyses to describe overall change in opioid prescribing during this time period and whether prescribing differed from before to after the OSI: >100 meq of opioids > 200 meq of opioid Opioid and benzodiazepine co-prescribing

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  intercept

P value

β 1 – original slope

P value

Β2 –immediate intervention effect

P value

β 3 –change in slope

P value

% > 100meq 9.82 <.0001

-.019 .0015 .15 .0083

-.035 .0001

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  intercept

P value

β 1 – original slope

P value Β2 –immediate intervention effect

P value

β 3 –change in slope

P value

% > 200meq

3.53 <.0001 -.016 <.0001 .017 <.0001

-.022 <.0001

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 240

5

10

15

20

25

All facilities combined, % of pts w/concurrent opioid & benzo fills by month

Oct 2012-Sept 2014

% o

f pt

s

  intercept P value β 1 – original slope

P value Β2 –immediate intervention effect

P value

β 3 –change in slope

P value

% w/ overlapping benzo’s & opioids

23.31 <.0001 -.185 <.0001 -.155 .5792 .158 .0137

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<-10 -10 to -5 -5 to 0 0 to 5 >50

5

10

15

20

25

30

35

40

Change in prescription of high-dose opioid fills following OSI rollout among VHA facilities

>100 mg>200 mg

% change

% o

f fa

cilit

ies

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Discussion: OSI and change in opioids

Use of higher dosages of opioids is decreasing in VHA The pace of this decrease appears to have accelerated post OSI

(especially for > 200 meq) Co-use of opioids and benzodiazepines is quite common. It

decreased over 2 years but no noticeable decrease associated with the OSI. Possible that it was not emphasized, or Harder to address

Caution – observational data on trends over time Significant variability in change pre-post OSI was observed

across VHA facilities. Highlighting: The difficulties in rolling-out national strategies to change care Opportunities to encourage use of strategies to improve the

impact of the OSI (e.g., the Minneapolis approach) throughout VHA

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General recommendations Understanding and quantifying the potential

implications of the expanded use of opioids for chronic pain requires an examination of multiple adverse outcomes (unintentional overdose, drugged driving, crime, heroin initiation, … suicide)

Health systems have played a significant role in the increased use of opioids and will need to invest in strategies to decrease opioid use.

Developing, evaluating and refining these strategies will help to reverse the trend of overuse of opioids and decrease the occurrence of opioid-related adverse outcomes

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Thank You!

Please feel free to contact me:

marki@med.umich.edu