Overdoses on Prescribed Opioids in Massachusetts, 2013-2014* AY Walley, MD, MSc,1,2 D Bernson, MPH,2 MR LaRochelle, MD, MSc,1 TC Green, PhD, MSc,1 L Young, MS, MA2 T Land, PhD2 1Boston Medical Center/ Boston University School of Medicine 2Massachusetts Department of Public Health AMERSA 2017

Chapter 55 www.mass.gov/eohhs/docs/dph/stop-addiction/current-statistics/data-brief-overdose-deaths-aug-2017.pdf

New Hampshire State Police Forensic Lab Chapter 55 www.mass.gov/eohhs/docs/dph/stop-addiction/current-statistics/data-brief-overdose-deaths-aug-2017.pdf

Heroin & Fentanyl Together Fatal opioid overdoses often attributed to prescribed opioids rather than diverted or street opioids Morphine Oxycontin Fentanyl patch Here you see examples of morphine medication, heroin, pharmaceutical fentanyl and illicit fentanyl. Heroin Alone Heroin & Fentanyl Together Fentanyl Alone

Study Aim Among people who died from opioid-related overdose in Massachusetts, determine the proportion of deaths with actively prescribed opioids where the days supply in the PMP overlaps the date of death and the opioid is in toxicology

Substance Use Treatment Methods Massachusetts Ch 55 dataset linked at individual level legislative mandate to characterize opioid overdose Massachusetts’ residents who died of an opioid-related overdose: 6/1/2013 -12/31/2015 PDMP All Payer Claims All residents with insurance ~ 6 Million Death Certificates Reduce the Substance Use Treatment Death Toxicology www.mass.gov/eohhs/gov/departments/dph/stop-addiction/chapter-55-overdose-assessment.html

Methods Among Massachusetts’ residents who died of an opioid-related overdose between 6/1/2013 and 12/31/2015, we analyzed individually-linked opioid toxicology and Prescription Monitoring Program (PMP) records Death and PMP records were available by specific date Methadone maintenance patients were available by month Claim for methadone administration from all payer claims database (HCPCS H0020) or Bureau of Substance Abuse Services treatment data Prescribed opioid overdoses definition: decedent had an active prescription, based on the number of days supplied in the PMP, for the opioid present in the toxicology prior to or on the date of death We also calculated the proportion of overdoses for which opioids prescribed in the PMP were not present in toxicology on the date of death We categorized samples that had 6-mam or a combination of morphine and codeine in the same sample as “heroin.” Whereas those with morphine, but no 6-mam or codeine, were categorized as “morphine”

Demographics of cohort of opioid-related deaths Analytic Cohort, opioid deaths with tox, 2013-15 n=2,916 Age, mean, median 39.4 (38) Gender Male 73% Female 27% Race White 87% Black 4.1% Asian/PI 0.4% Hispanic 7.7% American Indian/Other 0.8%

Heroin and fentanyl are the most common opioids in toxicology at death

Opioids commonly prescribed within 1 year of death, but uncommonly prescribed at time of death 1. To the 2. What fraction of the Active Rx’s are buprenorphine or MMT? I would like to further break these out: No opioid prescription Any bup or MMT No bup or MMT, but opioid Rx for pain Frequencies based on the number of days supplied in the PMP At death: MME mean 134, min 2, 25th 30, median 90, 75th 120, max 960

Active prescriptions are uncommon at death, especially fentanyl Prescribed opioid = Opioid with active prescription at death based on the # of days supplied in the PMP MMT = Methadone Maintenance within 1 month of death

Oxycodone, methadone, buprenorphine are most common actively prescribed opioids at death Fentanyl is not due to cell suppression rules at MDPH. There were 17 people who died with an active fentanyl prescription and fentanyl in toxicology. There were <5 people with an active fentanyl prescription who died without fentanyl in toxicology. Methadone MT = Methadone Maintenance within 1 month of death

Opioids prescribed were commonly NOT present on overdose toxicology Fentanyl is not due to cell suppression rules at MDPH. There were 17 people who died with an active fentanyl prescription and fentanyl in toxicology. There were <5 people with an active fentanyl prescription who died without fentanyl in toxicology. Methadone MT = Methadone Maintenance within 1 month of death

Limitations We did not incorporate opioid-specific information from death certificates because they were not systematically available or consistent Methadone maintenance information available at the month level Thus people who died in the month discharged from methadone are counted as being treated with methadone maintenance We did not include non-opioid substances e.g. benzodiazepines, alcohol, cocaine) Emerging, but non-prescribed, opioids (eg, carfentanil, furanyl fentanyl) were not routinely tested and not included

Conclusions Active prescriptions are uncommon at death, especially fentanyl More likely illicitly made fentanyl than prescribed Opioids commonly prescribed often not present on toxicology People who die often not taking prescribed opioid Except methadone – opioid with highest proportion prescribed, and thus lowest proportion diverted among people who die Linking overdose toxicology to PMP can better attribute overdoses to: prescribed opioids diverted prescription opioids heroin illicitly-made fentanyl

Thank you! awalley@bu.edu

ICD-10 cause of death codes do not distinguish heroin from morphine or pharmaceutical from illicit fentanyl T40.1 = heroin overdose, T40.2 = natural and semi-synthetic opioids (e.g. prescribed morphine) >> misclassification of heroin overdoses into T40.2 when only morphine is present T40.3 = synthetic opioids, excluding methadone (e.g. fentanyl, prescribed or illicit) 6-MAM, the specific toxicology result for heroin, is helpful when present, but does not rule out heroin when it is absent Commonly morphine is the only opioid substance detected after heroin overdose The current coding of causes of death system does not clearly distinguish heroin from morphine deaths or pharmaceutical fentanyl from illictly made fentanyl deaths. We categorized samples that had 6-mam or a combination of morphine and codeine in the same sample as “heroin.” Whereas those with morphine, but no 6-mam or codeine, were categorized as “morphine We categorized samples that had 6-mam or a combination of morphine and codeine in the same sample as “heroin.” Whereas those with morphine, but no 6-mam or codeine, were categorized as “morphine Harruff, R. C., F. J. Couper, and C. J. Banta-Green. "Tracking the opioid drug overdose epidemic in King County, Washington using an improved methodology for certifying heroin related deaths." Academy Forensic Pathology 5 (2015): 499-506.

2,916 opioid deaths with complete Results 1/2011-12/2015 5170 opioid deaths 6/2013-12/2015 3,710 opioid deaths 6/2013-12/2015 2,916 opioid deaths with complete toxicology results 79%

Overdoses involving IMF are acute and rapid CDC-Mass DPH mixed methods investigation that included death record reviews and qualitative interviews with people who use opioids and had either witnessed or survived an overdose Illicitly manufactured fentanyl (IMF) responsible for opioid overdose deaths “So, now what they [people selling illicit drugs] are doing is they’re cutting the heroin with the fentanyl to make it stronger. And the dope [heroin] is so strong with the fentanyl in it, that you get the whole dose of the fentanyl at once rather than being time-released [like the patch]. And that’s why people are dying—plain and simple. You know, they [people using illicit drugs] are doing the whole bag [of heroin mixed with fentanyl] and they don’t realize that they can’t handle it; their body can't handle it.” Overdoses involving IMF are acute and rapid “A person overdosing on regular dope [heroin] leans back and drops and then suddenly stops talking in a middle of a conversation and you look over and realize that they’re overdosing. Not like with fentanyl. I would say you notice it [a fentanyl overdose] as soon as they are done [injecting the fentanyl]. They don’t even have time to pull the needle out [of their body] and they’re on the ground.”

MDPH Chapter 55 – BMC Group Table of Approved Projects Lead investigator Co-Investigators Working title – topic Barocas Bernson, Camona, Walley, Linas Prevalence of opioid use disorder in the population – Capture/Recapture methodology Larochelle Bernson, Land, Stopka, Liebschutz, Walley Medication for opioid use disorder following nonfatal opioid overdose and association with mortality Walley Bernson, LaRochelle, Green, Young, Land Linking toxicology at death with prescription monitoring program records: implications for defining fentanyl and heroin-related deaths Rose Bernson, Chui, Land,Walley, LaRochelle, Stein, Stopka Potentially Inappropriate Opioid Prescribing, Overdose, and Mortality in Massachusetts, 2011-2015 Stopka Amaravdi, Kaplan,Hoh, Bernson,Chui, Land, Walley, LaRochelle, Rose Opioid Overdose Deaths and Potentially Inappropriate Opioid Prescription Practices (PIP): A Spatial Epidemiological Approach Morgan Jaeger, Nguyen, Walley, Linas Defining the cascade of care for substance use disorder detoxification in Massachusetts Bagley Larochelle, Walley, Hadland, Bernson, Land, Xuan, Samet Time to treatment or overdose among emerging adults presenting or NFOD- Characteristics of emerging adults who overdose Hadland Larochelle, Walley, Bagley, Samet Receipt of Pharmacotherapy among Adolescents and Young Adults with Opioid Use Disorder and its Impact on Fatal and Non-Fatal Overdose Park Larochelle, Walley, Saitz Prescribing of benzodiazepines and stimulants among people with OUD>>retention and overdose Larochelle, Babakhanlou-Chase, Land, Bernson Factors Associated with Overdose Death Among Inpatient Detoxification Patients Kimmel Linas, Larochelle, Walley Effect of treatment for opioid use disorder on opioid-related death among patients with intravenous drug associated endocarditis Green, Stopka, LaRochelle, Ruiz Community distribution of naloxone kits and naloxone rescues Lunze and Ventura Larochelle, Walley Mandated treatment of persons with substance use disorders in Massachusetts: Cohort description and correlates

Self-protective measures often employed Naloxone reverses overdoses involving IMF; multiple doses often required “So he put half [one dose] up one nose [nostril] and half [one dose] up the other nose, like they trained us to do, and she didn’t come to. So he put water on her face and kind of slapped her, which doesn’t really make you come to [regain consciousness]. It doesn’t. So he pulled out another thing of Narcan [brand of naloxone] and he put half of it [another dose] up one nose and then she came to…She just didn’t remember anything. She said, ‘What happened? I remember washing my hands and, like, what happened?’ We said, ‘You just overdosed in this room!’ So yeah, it was wicked scary.” Self-protective measures often employed “Like I will do a very, very, very little bit of fentanyl…and if I don’t feel it, I will do that little bit plus half. I’m just not going to throw the whole thing in the cooker and then do it, no way. I just know better.” Co-use of opioids and benzodiazepines “My daughter’s mother had benzos. And when she did one bag of heroin she already had done four or five Klonopin [brand of clonazepam] and she just died. That was it. She went into a coma for the night and she was dead in the morning.”

A comprehensive public health response to address overdoses related to IMF Fentanyl should be included on standard toxicology screens Adapt existing harm reduction strategies, such as direct observation of anyone using illicit opioids, ensuring bystanders are equipped with naloxone Enhanced access and linkage to medication for opioid use disorders

Demographics of cohort of opioid-related deaths Analytic Cohort, opioid deaths with tox, 2013-15 n=2,916 All opioid-related deaths, 2011-15 n=5,170 Age, mean, median 39.4 (38) 39.9 (39) Gender Male 73% 71% Female 27% 29% Race White 87% 88% Black 4.1% 4.0% Asian/PI 0.4% Hispanic 7.7% 7.1% American Indian/Other 0.8% 0.9%