Controlled Substance Prescribing Trends and Odds of Drug Overdose Death

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Controlled Substance Prescribing Trends and Odds of Drug Overdose Death Christina Holt, MD, MSc 1, Kenneth McCall, PharmD 2 Gary Cattabriga, BA 3, Emily Bourret, PharmD 2, Chunhao Tu, PhD 2 ; Christian Teter, PharmD 2, Todd Michaelis, MD 1 1. Maine Medical Center, Department of Family Medicine, Portland, ME 2. College of Pharmacy, University of New England, Portland, ME 3. Center for Community & Public Health, University of New England, Portland, ME

Objective Evaluate controlled substance prescribing trends and physician and pharmacy utilization patterns among persons who died of prescription drug overdose in Maine.

Methods Design: Retrospective data analysis of the Maine Prescription Monitoring Program (PMP) from fiscal years 2005 2010 linked to Medical Examiner Cases of all prescription drug deaths.

Limitations and Strengths Maine PMP does not include VA Healthcare System controlled prescriptions. Maine PMP does not include all Methadone Clinic prescriptions. Maine PMP does not include prescriptions filled outside of the State. Findings from rural states such as Maine may not apply to other states. Inclusion of all deaths in Maine for the time period. Inclusion of all controlled substance prescriptions dispensed by licensed pharmacies from 2005-2010 for decedents. Toxicology labs for all deaths performed by the same laboratory. Data linked over time (Patient identifier stays the same) Data linked across provider.

Study Population Maine PMP (2005-2010): 1,016,283 unique patients with 11,542,850 controlled substance prescriptions. Rx Drug Overdose Deaths (2005-2010): 1,007 drug overdose deaths overall 317 decedents did not have any PMP records 690 decedents with 31,736 controlled substance prescriptions in the PMP.

Matched Peer Group The 690 decedents of drug overdose death were matched to a peer group of patients with PMP records by: Age ± 2 years Gender County Having 1 or more prescriptions in the PMP within ±365 days of the decedent date of death The ratio of subjects in the peer group to the decedents is 50:1, thus 34,500:690.

Table 1: Demographic Characteristics of the Study Populations

Table 2: Substances found in toxicology screening and found contributory to 690 pharmaceutical overdose deaths, Maine, 2006-2010. Contributory Prescription Drug Found in Toxicology screen of prescription overdose deaths, Total (%) a Percent of patients to whom this drug dispensed within 90 days of death, % b Other category of contributory Substances found in toxicology screen, % Additional Prescription Opioids c Benzodiazepines Illicit Drugs e Alcohol Methadone 225 (32.6%) 13.3 24.9 29.3 10.7 10.7 Oxycodone 146 (21.2%) 44.5 44.5 37.0 7.5 16.4 Morphine 87 (12.6%) 20.7 31.0 24.1 17.2 17.2 Hyrdrocodone 61 (8.9%) 42.6 62.3 36.1 4.9 16.4 Fentanyl 31 (4.5%) 38.7 51.6 25.8 6.5 6.5 Other Opioids f 43 (6.2%) 67.4 58.1 32.6 16.3 11.6 Benzodiazepines d 159 (23.1%) 42.4 86.8 NA 7.9 13.9 Other drugs g 185 (26.8%) NA 67.6 27.0 5.4 15.7

Table 3: PMP Variables within 90 Days of the Index Date

Figure 1: Odds of overdose death by number of prescribers, pharmacies, or prescriptions within 90 days of index date within study cohort* * Unadjusted odds ratio of number of prescribers, prescriptions, or pharmacies per person compared to individuals with only one prescriber, prescription, or pharmacy.

Table 4: Peak Daily Opioid Dosage within 90 days of Index Date MORPHINE-MG- DECEDENTS MATCHED PEERS PMP Population EQUIVALENT N (%) N (%) N (%) 1-24 29 (4.2%) 552 (1.6%) 23,017 (2.3%) 25-99 142 (20.6%) 2,567 (7.4%) 77,750 (7.7%) 100-199 93 (13.5%) 474 (1.4%) 16,461 (1.6%) 200-299 47 (6.8%) 81 (0.2%) 3,569 (0.4%) 300-399 23 (3.3%) 31 (0.1%) 1,793 (0.2%) >400 60 (8.7%) 60 (0.2%) 1,914 (0.2%)

Table 5: Proportion of Decedents with a Controlled Substance Rx within 30 or 90 days of the index date that matches the toxicology cause of death

Figure 2: Odds ratio of overdose death by peak daily opioid dosage and percent of decedents with a PMP prescription within 90 days of index date that matches the cause of death ( % Matched Rx )* * Unadjusted odds ratio of peak daily opioid dosage per person as measured in morphine-mg-equivalents (MME) compared to individuals with 1-24 mg/day peak opioid dosage, comparing decedents to matched peers. The range of opioid dosage was divided into the following MME intervals: 1-24, 25-99, 100-199, 200-299, 300-399, 400-499, and >500 such that the X coordinates are the mean number of MME within each interval.

-349-333 -319-304 -291-277 -252-239 -231-215 -204-187 -180-173 -158-152 -146-137 -124-121 -116-113 -103-99 -93-88 -79-75 -69-62 -59-55 -52-48 -45-42 -39-36 -33-30 -27-24 -21-18 -15-12 -9-6 -3 Decedents Time lapse between date of last prescription dispensed and date of death 60 50 40 30 20 10 0 Days prior to date of death

Acknowledgments: Office of Substance Abuse, PMP Program Coordinators: Daniel Eccher, Patricia Lapera and John Liposky Medical Examiner s Office: Margaret Greenwald, MD, Chief Medical Examiner UMO Margaret Chase Smith Policy Center: Marcella Sorg, PhD Funding from UNE, MMC and AAFP

References 1. Substance Abuse and Mental Health Services Administration. (2010). Results from the 2009 National Survey on Drug Use and Health: Volume I. Summary of national findings (Office of Applied Studies, NSDUH Series H-38A, HHS Publication No. SMA 10-4586 Findings). Available at http://www.samhsa.gov/data/2k9/2k9resultsweb/web/2k9results.pdf 2. U.S. Center for Disease Control. (2010). Number of poisoning deaths involving opioid analgesics and other drugs or substances United States, 1999 2007. Morbidity and Mortality Weekly Report, 59(32), 1026. 3. Centers for Disease Control and Prevention. Unintentional poisoning deaths United States, 1999-2004. MMWR Morb Mortal Wkly Rep. 2007; 56(5):93-96. 4. Sorg MH. Drug-induced Deaths in Maine 1997-2008, with Estimates for 2009. Available at http://www.maine.gov/dhhs/samhs/osa/pubs/data/2011/druginduceddeathsreport%2097-08%20final%202[1].pdf 5. Hall, A. J., Logan, J. E., Toblin, R. L., Kaplan, J. A., Kraner, J. C., Bixler, D., & Paulozzi, L. J. (2008). Patterns of abuse among unintentional pharmaceutical overdose fatalities. JAMA, 300(22), 2613 2620. 6. Peirce GL, Smith MJ, Abate MA, Halverson J. Doctor and Pharmacy Shopping for Controlled Substances. Medical Care. 2012;50:494-500. 7. Paulozzi LJ, Jones CM, Mack KA, et al. Vital signs: overdoses of prescription opioid pain relievers United States, 1999 2008. MMWR. 2011;60:1 6. 8. McCall KL, Tu C, Lacroix M, Holt C, Wallace KL, Balk J. Controlled substance prescribing trends and physician and pharmacy utilization patterns: epidemiological analysis of the Maine Prescription Monitoring Program from 2006 to 2010. Journal of Substance Use (doi: 10.3109/14659891.2012.685794)