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Original Investigation |

Rates of Opioid Dispensing and Overdose After Introduction of Abuse-Deterrent Extended-Release Oxycodone and Withdrawal of Propoxyphene

Marc R. Larochelle, MD, MPH1,2; Fang Zhang, PhD1; Dennis Ross-Degnan, ScD1; J. Frank Wharam, MBBCh, BAO, MPH1
[+] Author Affiliations
1Harvard Pilgrim Health Care Institute, Department of Population Medicine, Harvard Medical School, Boston, Massachusetts
2Section of General Internal Medicine, Department of Medicine, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts
JAMA Intern Med. 2015;175(6):978-987. doi:10.1001/jamainternmed.2015.0914.
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Importance  In the second half of 2010, abuse-deterrent extended-release oxycodone hydrochloride (OxyContin; Purdue Pharma) was introduced and propoxyphene was withdrawn from the US market. The effect of these pharmaceutical market changes on opioid dispensing and overdose rates is unknown.

Objective  To evaluate the association between 2 temporally proximate changes in the opioid market and opioid dispensing and overdose rates.

Design, Setting, and Participants  Claims from a large national US health insurer were analyzed, using an interrupted time series study design. Participants included an open cohort of 31.3 million commercially insured members aged 18 to 64 years between January 1, 2003, and December 31, 2012, with median follow-up of 20 months (last follow-up, December 31, 2012).

Exposures  Introduction of abuse-deterrent OxyContin (resistant to crushing or dissolving) on August 9, 2010, and market withdrawal of propoxyphene on November 19, 2010.

Main Outcomes and Measures  Standardized opioid dispensing rates and prescription opioid and heroin overdose rates were the primary outcomes. We used segmented regression to analyze changes in outcomes from 30 quarters before to 8 quarters after the 2 interventions.

Results  Two years after the opioid market changes, total opioid dispensing decreased by 19% from the expected rate (absolute change, −32.2 mg morphine-equivalent dose per member per quarter [95% CI, −38.1 to −26.3]). By opioid subtype, the absolute change in dispensing by milligrams of morphine-equivalent dose per member per quarter at 2 years was −11.3 (95% CI, −12.4 to −10.1) for extended-release oxycodone, 3.26 (95% CI, 1.40 to 5.12) for other long-acting opioids, −8.19 (95% CI, −9.30 to −7.08) for propoxyphene, and −16.2 (95% CI, −18.8 to −13.5) for other immediate-release opioids. Two years after the market changes, the estimated overdose rate attributed to prescription opioids decreased by 20% (absolute change, −1.10 per 100 000 members per quarter [95% CI, −1.47 to −0.74]), but heroin overdose increased by 23% (absolute change, 0.26 per 100 000 members per quarter [95% CI, −0.01 to 0.53]).

Conclusions and Relevance  Opioid dispensing and prescription opioid overdoses decreased substantially after 2 major changes in the pharmaceutical market in late 2010. Pharmaceutical market interventions may have value in combatting the prescription opioid overdose epidemic, but heroin overdose rates continue to increase. Complementary strategies to identify and treat opioid abuse and addiction are urgently needed.

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Figure 1.
Standardized Prescribing Rates and Segmented Regression Results Before and After Introduction of Abuse-Deterrent Extended-Release Oxycodone Hydrochloride and Withdrawal of Propoxyphene

Extended-release oxycodone hydrochloride (OxyContin and generic products combined), other long-acting opioid formulations, and immediate-release propoxyphene and other opioids. Dashed vertical lines indicate the time of introduction of abuse-deterrent OxyContin (third quarter [Q] of 2010) and withdrawal of propoxyphene (Q4 of 2010). MED indicates morphine-equivalent dose.

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Figure 2.
Standardized Overdose Rates and Segmented Regression Results Before and After Opioid Market Changes

Dashed vertical lines indicate the time of introduction of abuse-deterrent OxyContin (third quarter [Q] of 2010) and withdrawal of propoxyphene (Q4 of 2010). MED indicates morphine-equivalent dose.

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Events Impacting Opioid Prescriptions and Overdose
Posted on May 11, 2015
Brian K. Ahmedani, L. Keoki Williams
Henry Ford Health System, Center for Health Policy and Health Services Research, 1 Ford Place, Suite 3A, Detroit, MI 48202
Conflict of Interest: Dr. Ahmedani receives grant funding from the National Institute of Mental Health, the National Institute on Aging, and the Ethel and James Flinn Foundation. Dr. Williams receives grant funding from the National Heart Lung and Blood Institute, the National Institute of Allergy and Infectious Diseases, and the National Institute of Diabetes and Digestive and Kidney Diseases.
We would like to thank Larochelle and colleagues for their interesting article regarding the effects on opioid dispensing and overdose due to both the withdrawal of propoxyphene from the U.S. market and the introduction of abuse-deterrent extended-release oxycodone.(1) Their findings support our earlier publication showing the effect of propoxyphene withdrawal in a large health system population in Michigan.(2) Given the proximity in time of propoxyphene withdrawal and abuse-deterrent oxycodone introduction, Larochelle et al. could not distinguish the relative effect of each event on overall opioid use. In contrast, in our study population, we observed that propoxyphene withdrawal was the opioid preparation negatively affected by the events of 2010 (preceded by a slow decline in propoxyphene use prior to 2010). Overall use of all other opioids, including oxycodone, remained fairly stable before and after 2010 with the exception of hydrocodone, which showed increasing use throughout. Corroboration of immediate-release hydrocodone as an important driver of the opioid epidemic is important given its previous designation as a more innocuous Schedule III drug when used in combination with non-opioid analgesics. Extended-release oxycodone without abuse deterrent features was introduced in 1995. Preparations with abuse deterrent features were introduced in 2010. While extended-release opioids have been associated with overdose deaths,(3) we found little evidence to suggest that this class is responsible for the large changes in overall opioid use. With the exception of propoxyphene, we did not observe a marked change in the pattern of opioid use circa 2010. Conversely, our data suggest that a precipitous increase in opioid use occurred 6 years after the introduction of extended-release oxycodone (i.e., with the promulgation of pain management policies). Therefore, Larochelle and colleagues could provide important supporting evidence and policy implications, if they could also assess the timing of the start (or acceleration) of the prescription opioid epidemic. Lastly, our study suggested a flattening in the rate of opioid-related overdoses and poisonings beginning in the mid-2000s. The National Center for Health Statistics showed a similar plateau in the opioid-related death rate beginning in the mid-2000’s.(4) However, the subset of poisoning-related deaths attributable to natural and semi-synthetic opioids (e.g., oxycodone and hydrocodone) continued to rise through 2011. Taken together, neither source demonstrated that the events of 2010 specifically resulted in a decline in rates of opioid overdose, even though observational data support a decline in Oxycontin as a reported drug of abuse.(5) Additional study is warranted.  REFERENCES1. Larochelle MR, Zhang F, Ross-Degnan D, Wharam JF. Rates of Opioid Dispensing and Overdose After Introduction of Abuse-Deterrent Extended-Release Oxycodone and Withdrawal of Propoxyphene. JAMA internal medicine. 2015.2. Ahmedani BK, Peterson EL, Wells KE, Lanfear DE, Williams LK. Policies and events affecting prescription opioid use for non-cancer pain among an insured patient population. Pain physician. 2014;17(3):205-216.3. Miller M, Barber CW, Leatherman S, et al. Prescription opioid duration of action and the risk of unintentional overdose among patients receiving opioid therapy. JAMA internal medicine. 2015;175(4):608-615.4. Chen LH, Hedegaard H, Warner M. Drug-poisoning Deaths Involving Opioid Analgesics: United States, 1999-2011. NCHS Data Brief. 2014(166):1-8.5. Cicero TJ, Ellis MS, Surratt HL. Effect of abuse-deterrent formulation of OxyContin. N Engl J Med. 2012;367(2):187-189.
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