Journal of Urban Health: Bulletin of the New York Academy of Medicine, Vol. 87, No. 6
`doi:10.1007/s11524-010-9495-8
`* 2010 The Author(s). This article is published with open access at Springerlink.com
`
`Overdose Prevention and Naloxone Prescription
`for Opioid Users in San Francisco
`
`Lauren Enteen, Joanna Bauer, Rachel McLean, Eliza Wheeler,
`Emalie Huriaux, Alex H. Kral, and Joshua D. Bamberger
`
`ABSTRACT Opiate overdose is a significant cause of mortality among injection drug users
`(IDUs) in the United States (US). Opiate overdose can be reversed by administering
`naloxone, an opiate antagonist. Among IDUs, prevalence of witnessing overdose events is
`high, and the provision of take-home naloxone to IDUs can be an important intervention to
`reduce the number of overdose fatalities. The Drug Overdose Prevention and Education
`(DOPE) Project was the first naloxone prescription program (NPP) established in
`partnership with a county health department (San Francisco Department of Public Health),
`and is one of the longest running NPPs in the USA. From September 2003 to December
`2009, 1,942 individuals were trained and prescribed naloxone through the DOPE Project,
`of whom 24% returned to receive a naloxone refill, and 11% reported using naloxone
`during an overdose event. Of 399 overdose events where naloxone was used, participants
`reported that 89% were reversed. In addition, 83% of participants who reported overdose
`reversal attributed the reversal to their administration of naloxone, and fewer than 1%
`reported serious adverse effects. Findings from the DOPE Project add to a growing body of
`research that suggests that IDUs at high risk of witnessing overdose events are willing to be
`trained on overdose response strategies and use take-home naloxone during overdose
`events to prevent deaths.
`
`KEYWORDS Overdose, Heroin, Naloxone, Injection drug user
`
`INTRODUCTION
`
`Drug-related deaths are the leading cause of injury mortality among all US adults
`aged 35 to 55.1 Opioids are one of the most commonly involved substances in single
`and polydrug use deaths.2 Opiate overdose is the single greatest cause of mortality
`among injection drug users (IDUs) in the USA3 and accounts for more than half of
`all deaths among opiate injectors, far exceeding the proportion due to HIV/AIDS
`and viral hepatitis.3,4 Opiate overdose deaths increased by 529% between 1990 and
`2003 across the USA.2 In addition, opioid analgesic-related deaths are among the
`fastest growing causes of drug poisoning deaths in the USA.1
`While loss of consciousness following overdose can at times be instantaneous,
`death is usually the result of cardiac arrest that follows hypoxia, which is the result of
`
`Enteen is with the Masters Entry Program in Nursing, University of California, San Francisco, CA, USA;
`Bauer and Bamberger are with the Housing and Urban Health, San Francisco Department of Public
`Health, San Francisco, CA, USA; McLean is with the California Department of Public Health, San
`Francisco, CA, USA; Wheeler is with the Drug Overdose Prevention and Education Project, Oakland,
`CA, USA; Huriaux is with the AIDS Office, San Francisco Department of Public Health, San Francisco,
`CA, USA; Kral is with the RTI International, San Francisco, CA, USA.
`Correspondence: Joshua D. Bamberger, Housing and Urban Health, San Francisco Department of
`Public Health, San Francisco, CA, USA. (E-mail: josh.bamberger@sfdph.org)
`
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`the opiate suppressing the central respiratory drive.5,6 The time from initial injection to
`death typically leaves a 1–3-h window for a witness to intervene.5,6 While this
`window would leave sufficient time for emergency personnel to respond, studies
`report that emergency medical services (EMS) are activated in fewer than half of
`overdose events.7–9 Although cardiopulmonary resuscitation can be an effective
`intervention during an overdose event,10 opiate overdose can almost universally be
`reversed by the administration of naloxone—a legal, nonscheduled opioid antagonist
`that can be quickly administered by intramuscular injection.10–12 Naloxone produces
`no symptoms of dependence or tolerance and, in the absence of narcotics, has no
`pharmacological activity.13 Naloxone is routinely administered by emergency services
`personnel to revive opiate overdose victims, and serious side effects are rare.14–17
`Yet, barriers to intervention and overdose reversal remain. Between 1997 and 2000,
`EMS response was noted in medical examiner's notes for only 26% of fatal opiate
`overdoses in San Francisco.8 In surveys, IDUs consistently report a high prevalence of
`witnessing overdose events,9,18–22 and in one Bay Area survey, 89% of participants
`reported witnessing an overdose event.9 However, IDUs also report reluctance to
`contact EMS as a witness.9,21–25 Qualitative research with IDUs indicates that fear of
`police is a significant barrier to calling emergency services (“9-1-1” in the USA) during
`an overdose event.21,23 IDUs report making other attempts to revive overdose victims
`without EMS assistance,9,21,22 and demonstrate willingness to administer naloxone
`during an overdose if it was made available to them directly.9,18,23,24 This indicates
`that targeted take-home naloxone prescription and overdose training programs may
`be an effective intervention to reduce opiate overdose deaths.
`In response to increased fatal opiate overdose, community-based programs
`began distributing naloxone directly to IDUs in Europe in 1995,26 and underground
`programs have been distributing naloxone in the USA since 1999.27 Take-home
`naloxone prescription programs (NPPs) are currently in place in locales throughout
`the USA, including large-scale NPPs in Chicago, Baltimore, New York City, New
`Mexico, and Massachusetts.27–29 NPPs typically provide overdose response
`education and naloxone administration training to IDUs and others at high risk of
`witnessing an opioid overdose, so that participants are able to administer naloxone
`safely and avert fatalities during overdose events.
`Preliminary evaluations of NPPs in several cities have found that overdose
`response education and naloxone administration training positively affects IDUs’
`ability to recognize overdose symptoms and identify cases where naloxone is
`indicated.24,28–30 Prospective pilot studies in Los Angeles32 and New York23,33 and
`San Francisco30 tracked small samples of IDUs who were trained and provided with
`naloxone. In New York and San Francisco, over half reported using naloxone
`during 3- or 6-month follow-up periods, and the proportion of participant-
`confirmed reversals ranged from 74%32 to 100%.23,30,33
`Fewer studies have examined outcomes of an NPP over an extended period of
`time. One longstanding NPP in Chicago reported training 3,500 participants from
`2001 to 2005, of whom 319 reported overdose reversals (9%).27 A program
`dispending intranasal naloxone in Massachusetts recently reported that 19% (74) of
`385 trained participants used naloxone after training.34
`In 2003, the San Francisco Department of Public Health (SFDPH) partnered
`with a community-based program, the Drug Overdose Prevention and Education
`Project (DOPE Project) to establish the first health-department sanctioned NPP in
`the US. Modeled on underground community based NPPs, the DOPE Project was
`the first NPP to receive staff and support from a county department of public health.
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`The goal of the DOPE Project is to integrate overdose prevention education and
`naloxone distribution into all settings serving people at risk for opioid overdose.31
`We present evaluation findings for the DOPE Project NPP in San Francisco,
`from the start of SFDPH partnership in September 2003 through December 2009.
`Our goal was to examine the number and demographics of trained participants
`prescribed take-home naloxone, as well as the prevalence of and reasons for
`receiving naloxone refills among trained participants. We present prevalence of
`naloxone administration among individuals receiving refills from the DOPE Project
`and outcomes of naloxone administration, including any negative effects reported
`and overall proportion of successful reversals.
`
`METHODS
`
`The San Francisco DOPE Project Intervention
`Since September 2003, DOPE Project staff and SFDPH medical providers have
`trained and distributed naloxone at sites throughout San Francisco that include
`syringe exchange programs (SEP), re-entry programs, pain management clinics,
`methadone maintenance and buprenorphine treatment programs, and single room
`occupancy (SRO) hotels. The DOPE Project currently conducts trainings and
`naloxone dispensations approximately eight times per month throughout San
`Francisco.
`Participants are usually recruited and trained while waiting to receive services at
`clinics, dropping off syringes at SEPs, or in group trainings in SROs and treatment
`programs. Trainings typically last between 10 and 30 minutes and focus on overdose
`symptom identification, revival strategies, calling EMS, and administering naloxone
`(Figure 1). After DOPE Project staff train participants, SFDPH medical providers
`initiate a medical record (clinical registration) and assign each participant a unique
`identifier. Providers prescribe and dispense naloxone in two 0.4-mg/mL vials and
`two 3-cm3/mL 22-gauge 1-in muscling syringes along with a rescue breathing mask.
`All trained participants with unique identifiers and clinical registrations may receive
`refills of two pre-filled syringes at any subsequent dispensation—when participants
`use naloxone, lose, or have naloxone confiscated. SFDPH providers do not limit the
`number of refills trained participants may receive.
`
`Data Collection
`All participants who receive take-home naloxone complete a brief questionnaire
`immediately following initial training. The questionnaire is voluntary, self-reported,
`and administered by DOPE Project or SFDPH staff. Information provided includes
`date of birth, gender, race/ethnicity, primary language, homeless status, and/or
`current housing.
`All participants who receive subsequent refills also complete an additional brief
`questionnaire. If receiving naloxone following a loss, participants describe “circum-
`stances of loss (e.g., stolen bag, taken by police, etc.).”
`Participants who receive refills following naloxone administration complete a
`brief interview with DOPE Project staff. The standard questionnaire captures
`to whom naloxone was administered (e.g., “girlfriend,”
`information about
`“spouse,” “friend,” “stranger,” “self”), and whether participants used other
`prevention strategies covered in DOPE Project training: sternum rub; awaken
`victims; call emergency services; rescue breathing; waited with them. Participants are
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`Mechanism of opiate overdose
`
`Risk factors for opiate overdose
`
`Prevention strategies
`
`Recognition
`
`Response
`
`Calling 9-1-1
`
`Administration of naloxone
`
`Rescue breathing
`
`Aftercare
`
`Naloxone care
`
`Logistics and refills
`Components of 10−30-min trainings conducted by DOPE Project staff
`FIGURE 1.
`participants receiving take-home naloxone.
`
`for all
`
`also asked whether an ambulance arrived, and to choose from among seven possible
`outcomes for the event: they [victim] woke up without any help; they woke up
`because of my help; paramedics came and revived the person [victim]; paramedics
`came and I do not know what happened next; they [victim] died; do not know; other
`(specify). Participants report any “negative consequences” of the overdose and
`naloxone administration that
`include: arrest of victim or witness; vomiting;
`harassment by police; harassment by paramedics; seizure; other (specify).
`
`Analysis
`All records used in this study were obtained as part of the DOPE Project routine
`program monitoring and evaluation. We considered all
`individuals who were
`trained, prescribed, and assigned a unique identifier (at clinical registration) as
`participants in the DOPE Project and used a clinical registration database (Microsoft
`Excel, Seattle, WA, USA) to calculate total number of trained participants, and
`participant demographics. Participants who reported being homeless, living at a
`shelter, transitional housing, or street or “couch surfing” were coded as unstably
`housed.
`A separate database of all refills is also maintained by the DOPE Project
`(Microsoft, Excel, Seattle, WA). Databases were linked by participants’ unique
`identifiers to determine the number of unduplicated participants who received refills
`following self-reported loss or use of naloxone, as well as the total number of losses
`and naloxone use reported, the proportion of individuals receiving multiple refills,
`and the proportion of individuals reporting multiple naloxone use. We excluded
`from analysis any records of refills where no unique identifier could be linked to an
`existing clinical registration (n=37).
`We coded reports stating that naloxone was taken by police, San Francisco
`Department of Public Works (DPW) or sheriff’s office as confiscation; all reports
`that naloxone was stolen, lost, or destroyed for any reason was coded as being lost.
`We use information captured in refill questionnaire to determine outcomes for
`trained participants who reported administering naloxone. Questionnaires were
`used to determine proportion of participants who used strategies other than
`naloxone, including contacting EMS. All events where participants reported that
`the victim was “revived” after naloxone administration are included here as
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`OVERDOSE PREVENTION AND NALOXONE PRESCRIPTION FOR OPIOID USERS
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`successful reversals—whether or not participants specifically attributed the reversal
`to naloxone administration. Questionnaires were also used here to report
`proportion of deaths, unknown outcomes, or any negative effects.
`
`RESULTS
`
`From September 2003 to December 2009, the DOPE Project and SFDPH medical
`providers trained and prescribed naloxone to 1,942 unduplicated individuals in San
`Francisco. The number of new participants increased steadily from 2003 to 2009,
`averaging 328 per year.
`The majority of participants were male (64%) and the median age at training
`was 40 years old (Table 1). Race/ethnicity was only captured for 75% of
`participants overall. Of
`these, 61% were Caucasian and 18% were African
`American. Housing status was reported by 88% of participants, of whom over half
`(59%) reported being homeless or unstably housed (not shown).
`Of the 1,942 participants who receive naloxone prescriptions, 24% returned to
`receive at least one naloxone refill (Table 2), of whom half returned on more than
`one occasion to receive multiple refills. Participants requested refills for a variety of
`reasons, including having naloxone stolen on the street, confiscated in a shelter, or
`destroyed during unstable housing transition. Of 1,020 refills dispensed, 399 (40%)
`were provided after participants reported using naloxone during an overdose event,
`
`TABLE 1 DOPE Project participants trained and prescribed 2003−2009 (n=1,942)
`
`Gender
`Male
`Female
`Transgender
`Unknown (not captured)
`Race/ethnicity
`Caucasian/White
`African American/Black
`Latino/a
`Asian/Pacific Islander
`Native American
`More than one race/ethnicity
`Other
`Unknown (not captured)
`Housing status
`Stable housing
`Homeless/unstably houseda
`Living in shelter
`Living in transitional housing
`Living on street
`Doubling up or “couch surfing”
`Homeless, no additional housing information
`Unknown housing status
`
`n
`
`1,239
`644
`15
`44
`
`901
`263
`131
`32
`35
`53
`51
`476
`
`618
`893
`127
`292
`241
`51
`182
`431
`
`(%)
`
`(64)
`(33)
`(1)
`(2)
`
`(46)
`(14)
`(7)
`(2)
`(2)
`(3)
`(3)
`(24)
`
`(32)
`(46)
`(7)
`(15)
`(12)
`(3)
`(9)
`(22)
`
`aIncludes both those who answered “yes” to homeless and those reporting living in shelter, transitional
`housing, or doubling up
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`TABLE 2 Participants who received refills from the DOPE Project, 2004−2009
`
`Participants who received at least
`one naloxone refill, any reason
`Participants who received multiple
`refills, any reason
`Participant who received at least one
`refill reporting naloxone loss
`Participants who received at least one
`refill reporting confiscation
`Participants who received at least one
`refill reporting naloxone administration
`during an overdose event
`Participants who received multiple
`refills reporting naloxone administration
`during multiple overdose events
`
`Of 1,942 participants trained 2003−2009
`
`n
`
`470
`
`219
`
`311
`
`79
`
`215
`
`95
`
`(%)
`
`(24)
`
`(11)
`
`(16)
`
`(4)
`
`(11)
`
`(5)
`
`while 49% were provided after participants reported a loss of naloxone, and 12%
`were provided after participants reported confiscation by police, DPW, or sheriff’s
`department (upon admission to jail). Of participants who lost naloxone, 27%
`reported that they also used naloxone in response to a subsequent overdose event.
`Overall, 11% of all participants reported using naloxone during an overdose
`event, and 5% reported using multiple prescriptions (refills) during more than one
`overdose event (Table 2). In addition, a small proportion of participants (not shown)
`reported using multiple naloxone doses to reverse as many as eight separate
`overdose events. The cumulative number of naloxone-administration events
`reported to the DOPE Project has risen steadily since 2004 (Figure 2), with an
`average of 80 events reported annually.
`In 83% of overdose responses reported, participants stated that naloxone
`administration reversed the overdose. Participants reported successful outcomes
`(reversal with or without EMS involvement) for 89% of all overdose events where
`
`450
`400
`350
`300
`250
`200
`150
`100
`50
`0
`
`2003
`
`2004
`
`2005
`
`2006
`
`2007
`
`2008
`
`2009
`
`Cumulative number of naloxone administrations during overdose events
`reported to the DOPE Project, by year
`
`FIGURE 2.
`Cumulative number of opioid overdose responses with naloxone reported by DOPE
`Project participants receiving refills, by year, 2003−2009.
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`naloxone was used (Table 3), and an additional 3% of reports indicated that EMS
`was contacted, but outcome was unknown.
`Three-quarters of participants who used naloxone also reported using
`complementary overdose prevention strategies taught by the DOPE Project such as
`rescue breathing (50%, Table 3). However, a minority (29%) reported calling
`emergency services, and only 21% of reports included indication that EMS arrived.
`Although only one participant reported arrest following naloxone administration,
`13% of the 84 participants who reported ambulance response also reported some
`harassment by police or EMS (Table 3).
`Serious adverse effects were reported rarely and included several instances of
`seizures (Table 3). In cases for which participants reported a known outcome,
`vomiting was the most commonly reported negative effect (13%), followed by
`“anger” or discomfort expressed by victim upon waking (9%). Three participants
`(G1%) reported witnessing a victim experience symptoms of a seizure following
`naloxone administration. Victim death was reported by participants in four (1%)
`events where naloxone was used (not shown). In three of these cases, participants
`reported that the victim had been unconscious for an undetermined amount of time
`
`TABLE 3 Participant reported responses and outcomes of opioid overdose events where
`naloxone was administered, among participants receiving a naloxone refill from the DOPE
`Project, 2004–2009 (n=399)
`
`Relationship between participant and overdose victim
`Participant used naloxone on companion (friend, spouse)
`Participant used naloxone on stranger
`Relationship between participant and victim not reported
`Participant reported naloxone was used on self during overdose
`Other overdose prevention strategies used in addition to naloxone
`Participant reported using any additional strategy
`Sternum rub
`Awaken victim
`Rescue breathing
`Participant reported calling 911 during the overdose event
`Participant reported ambulance response
`Participant reported outcome of overdose event
`Reversed, all reasons
`Reversed due to participant administering naloxone
`Reversed following EMS response
`Naloxone administered, but victim revived by another method
`Victim died
`Outcome Unknown
`Other adverse outcomes reported
`Seizure
`Vomiting
`Victim was angry or “dope sick”
`Arrest
`EMS/police harassment
`
`N
`
`142
`60
`111
`85
`
`298
`123
`127
`199
`116
`84
`
`357
`333
`19
`5
`6
`36
`
`3
`50
`36
`1
`11
`
`(%)
`
`(36)
`(15)
`(28)
`(21)
`
`(75)
`(31)
`(32)
`(50)
`(29)
`(21)
`
`(89)
`(83)
`(5)
`(1)
`(2)
`(9)
`
`(1)
`(13)
`(9)
`(.2)
`(3)
`
`Of 399 overdose events where participants administered naloxone, as reported to DOPE Project by
`participants receiving naloxone refills, 2004−2009
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`before they were found, including one victim who was found unconscious in a large
`public park.
`
`DISCUSSION
`These findings are the first to examine overall participant demographics for a
`longstanding NPP, and indicate that the DOPE Project is well targeted to reach
`participants who are at high risk of overdose. For example, we found that 46% of
`those trained by the program identified as unstably housed or homeless, which has
`been associated with significantly elevated risk of overdose death in previous studies
`of overdose in San Francisco.29 Moreover, by targeting the program in places where
`there is a high prevalence of IDUs who witness overdose events, the DOPE Project
`has trained a steady population of newly prescribed participants, many of whom
`return to receive refills on multiple occasions, which further indicates that they are
`not only willing to be trained, but also motivated to keep a naloxone supply
`available for use during an overdose.
`We found a substantial proportion of trained participants who reported using
`naloxone, and the proportion found here was consistent with reports from the
`Chicago Recovery Alliance, one of the largest NPPs in the USA.27 Additional
`previous studies have focused on prospectively tracked small samples and targeted
`follow up,23,30,32,33 making utilization and reversal rates difficult to compare to our
`findings. However,
`these studies consistently find high proportions of
`that
`participants reporting naloxone use at follow up may suggest that the proportion
`of participants who report naloxone utilization at refill is an underestimate of the
`overall proportion of participants who use naloxone after training.
`We found that the majority of individuals who used naloxone during an
`overdose event also indicated that they used other revival methods taught during
`DOPE trainings. However, a minority reported contacting EMS. An earlier survey of
`IDUs in San Francisco found that 62% reported they would be “less inclined” to
`contact EMS if they had naloxone.8 That 84% of participants who used naloxone
`reported successful reversal without EMS intervention may suggest that IDUs did
`not call EMS because they did not deem it necessary, given successful reversal.
`Among participants who did not know the outcome of the overdose event, calling
`EMS was more common. Nevertheless, calling emergency services is an important
`component of training, and efforts should continue to be made to assess and address
`IDU barriers to contacting EMS during an overdose event, as well as continuing to
`provide naloxone education and prescription.
`Among participants who reported using naloxone, the majority reported
`positive and successful experiences. Findings here on rates of success per event
`reported were within the range found in previous studies.32,34 Reports of adverse
`events were rare (G1% reported victim seizure following naloxone administration).
`In addition, although six deaths were reported, there was no indication that this was
`due to naloxone administration and may have been cases where individuals had
`been experiencing the overdose for several hours before a witness arrived. Our
`findings indicate that IDUs can and will successfully administer naloxone with brief
`training, intervening during overdose events that may otherwise be fatal.
`
`Limitations
`There were several methodological limitations that we encountered while interpret-
`ing our findings. All
`information is self-reported by participants and could be
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`affected by social desirability or recall bias among participants completing the refill
`questionnaire. Due to participant non-disclosure, missing information about race/
`ethnicity and housing status made it difficult to assess any trends in refill receipt or
`naloxone use by these characteristics. Findings reported about naloxone admin-
`istration and outcome excluded seven reports where unique identifiers could not be
`matched to clinical registrations. However, no serious adverse outcomes were
`reported in excluded records.
`Our findings on naloxone use here is limited to participants who received refills.
`DOPE Project staff made no attempts to actively follow up with other participants.
`Therefore, we cannot determine an exact proportion of reversal, loss, or confiscation
`among participants overall. It is similarly difficult to draw conclusions about the
`actual
`incidence of adverse effects following naloxone administration. Unfortu-
`nately, we did not collect detailed information in our structured questionnaire about
`the extent of the non-fatal adverse events. As such, we cannot know the extent of the
`symptoms of seizures, which could have ranged from tonic-clonic activity to slight
`alterations of consciousness. Individuals with positive experiences may have been
`more likely to request refills than those with negative experiences using naloxone.
`However, few adverse effects were reported, and the proportion of reported deaths
`from unsuccessful reversals was similar to other NPP evaluations.27,32,34
`
`CONCLUSION
`This is the first longitudinal evaluation of participants, refill request, naloxone use,
`and outcomes among IDUs participating in a take-home naloxone prescription
`program in San Francisco. Participation has grown steadily among individuals at
`high risk of witnessing overdose events, and findings indicate that participants are
`motivated to receive refills following naloxone loss or use. Among trained
`participants who report using naloxone, nine in 10 report positive outcomes. Few
`serious side effects or deaths were reported. The findings presented here add to a
`growing body of evidence that supports the positive impact of NPPs as an
`intervention to prevent potentially fatal overdose events.
`
`ACKNOWLEDGEMENTS
`
`The authors are grateful to the staff and trainers of the DOPE Project and SFDPH
`medical providers for their contribution to management of the program. Assistance
`with data collection and management was provided by DOPE Project staff and
`SFDPH medical providers. This manuscript is dedicated to the memory of Peter
`Morse, Ph.D., whose extraordinary work improved the lives of so many of us.
`
`OPEN ACCESS This article is distributed under the terms of the Creative Commons
`Attribution Noncommercial License which permits any noncommercial use,
`distribution, and reproduction in any medium, provided the original author(s) and
`source are credited.
`
`REFERENCES
`
`1. Warner M, Chen LH, Makuc DM. Increase in fatal poisonings involving opioid
`analgesics in the United States, 1999–2006. NCHS data brief, no. 22. Hyattsville, MD:
`National Center for Health Statistics; 2009.
`
`Opiant Exhibit 2191
`Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.
`IPR2019-00694
`Page 9
`
`

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`
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`Opiant Exhibit 2191
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`Page 10
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