Hillary V. Kunins

Opioid Analgesics—Risky Drugs, Not Risky Patients

FROM 1999 TO 2010 THE NUMBER OF PEOPLE IN the United States dying annually from opioid analgesic–related overdoses quadrupled, from 4030 to 16 651. Patients’ predisposition to overdose could not have changed substantially in that time; what has changed substantially is their exposure to opioids. During this same time, the amount of opioids prescribed also quadrupled. The increase in prescribing occurred in the context of a greater emphasis on treating pain following efforts by the American Pain Society, the Veterans Health Administration, The Joint Commission, and others to increase recognition and management of pain, as well as advocacy by pain societies urging physicians to use opioids more readily for patients with chronic noncancer pain. Even though it is well known that prescription opioid use can lead to addiction or overdose, some opioid manufacturers and pain specialists suggest that few patients are susceptible to these risks. To distinguish low-risk from highrisk patients, use of screening tools, including the Screener and Opioid Assessment for Patients with Pain, has been advocated. Medication guides include statements such as “the chance [of abuse or addiction] is higher if you are, or have been, addicted to or abused other medicines, street drugs, or alcohol, or if you have a history of mental problems.” While there is likely to be a gradient of risk across patients, this statement may reassure clinicians that people with opioid addiction are different from most patients for whom they provide care. However, opioid dependence is much more common than previously believed and has been estimated to affect more than one-third of patients with chronic pain. No screening tool has sufficiently high sensitivity to rule out problems with opioids. Reported sensitivities of these tests for observed “aberrant drug-related behavior” (eg, dose escalation outside the treatment plan or forging prescriptions) among patients with chronic pain are generally within a range between 70% and 90%, which means that they miss 10% to 30% of patients at high risk of misuse or addiction. In addition, some industry-sponsored educational brochures suggest that physicians should ignore signs of opioid dependence in low-risk patients. For instance, some patients might not be considered at high risk of misuse even though they may use more opioids than prescribed (one definition of misuse). Some authors have stated that behaviors such as taking more opioids than prescribed may represent pseudoaddiction, a concept introduced in a case report in 1989 as “abnormal behavior developing as a direct consequence of inadequate pain management.” However, this concept remains untested, without scientific studies validating diagnostic criteria or describing long-term clinical outcomes. Nonetheless, some pain societies have promoted this concept and suggest that some patients demonstrating behaviors typical of opioid addiction may actually require higher doses. Rather than representing iatrogenic undertreatment of pain, however, behaviors described as pseudoaddiction may represent predictable responses to opioid exposure. Longterm opioid use typically results in tolerance. A standard clinical solution is to increase opioid dose. However, contrary to the view that there is no maximum safe dose if opioids are increased gradually over time, death from opioid overdose becomes more likely at higher doses. The most important risk factor for opioid analgesic– associated dependence or overdose is not a feature of any individual patient but instead simply involves receiving a prescription for opioids. For example, newly prescribed opioids after short-stay surgery are associated with a 44% increase in risk of becoming a long-term opioid user within 1 year. Another potential complication of screening for risk of opioid abuse is that identifying patients who should not receive opioids can stigmatize them, leading to consequences that do not help them. Patients who are questioned about substance use and then excluded from an expected treatment may feel embarrassed or abandoned. The decision to address a patient’s pain should not depend on

Guidelines for opioid prescription: why emergency physicians need support.

In January 2013, the New York City Department of Health and Mental Hygiene released guidelines to help reduce the misuse of prescription opioid analgesics by establishing standards for prescribing ...

Public Health Detailing-A Successful Strategy to Promote Judicious Opioid Analgesic Prescribing.

OBJECTIVESnTo evaluate knowledge and prescribing changes following a 2-month public health detailing campaign (one-to-one educational visits) about judicious opioid analgesic prescribing conducted among health care providers in Staten Island, New York City, in 2013.nnnMETHODSnThree detailing campaign recommendations were (1) a 3-day supply of opioids is usually sufficient for acute pain, (2) avoid prescribing opioids for chronic noncancer pain, and (3) avoid high-dose opioid prescriptions. Evaluation consisted of a knowledge survey, and assessing prescribing rates and median day supply per prescription. Prescribing data from the 3-month period before the campaign were compared with 2 sequential 3-month periods after the campaign.nnnRESULTSnAmong 866 health care providers visited, knowledge increased for all 3 recommendations (Pu2009<u2009.01). After the campaign, the overall prescribing rate decreased similarly in Staten Island and other New York City counties (boroughs), but the high-dose prescribing rate decreased more in Staten Island than in other boroughs (Pu2009<u2009.01). Median day supply remained stable in Staten Island and increased in other boroughs.nnnCONCLUSIONSnThe public health detailing campaign improved knowledge and likely prescribing practices and could be considered by other jurisdictions to promote judicious opioid prescribing.

Abuse-Deterrent Opioid Formulations: Part of a Public Health Strategy to Reverse the Opioid Epidemic

Rapid increases in the supplyofopioid analgesicshave largely driven the nearly unremitting increase in overdose deaths in the United States, which have grown bymore than 150%over thepast decade, from16 849 in 1999 to41 502 in 2012.1,2 Since the 1990s, opioid analgesic sales have increased more than 4-fold,with risingandwidely variable regional prescribing patterns. Increased market supply makes opioids more available for misuse and diversion to people engaging in recreational use and topeoplewith addiction. In both cases,misuseanddiversion increase, elevatingpopulationoverdose risk. In fact, geographic areas with higher opioid prescribing rates experience higher overdose rates.2 In addition, patient-level data demonstrate that the intensity of opioid exposure, includinghigherprescribeddosesand longerdurationof therapy, elevates overdose risk.3,4 Given this opioid-overdose epidemic, the clinical literature isunderstandably repletewithefforts that target individuals most at risk, including strategies such as routine screening for risk of addiction, patient agreements, andurine toxicologymonitoring.Unfortunately, these approaches havenot yet demonstratedwidespread effectiveness in reversing the epidemic.5 Public health approaches to reduce opioid-related overdosesarealsoneeded,sincemostoverdosesdonotoccuramong patients who are receiving daily prescribed opioids or among those receiving thehighestdosesdespite the fact thatdoseand daily use confer elevated risk at an individual level.2 In this issueofJAMAInternalMedicine,Larochelleandcolleagues6highlight the critical importance of one public health lever: market supply of opioids. The authors studied 2 nearly simultaneously implementedpharmaceuticalmarket changes among commercial health plan beneficiaries: substitution of abuse-deterrent long-actingoxycodonehydrochloride (which reducespotential tamperingof its time-releasemechanism) for the non–abuse-deterrent formulation and the removal of the weak opioid propoxyphene. Following thesemarket changes, the rate of nonfatal emergency department visits and inpatient visits for opioid analgesic overdoses decreased. The pharmaceutical market changes were also associated with a decrease in overall milligrams of morphineequivalent doses (MEDs) dispensed, resulting in adecrease of dispensed opioid dose per covered beneficiary from a high of 163 mg MED in late 2010 to 139 mg MED in early 2012. These market changes in the opioid supply may have reduced the numbers of overdoses for several reasons. With fewer opioids prescribed, beneficiaries with prescriptions consumed less, lowering individual risk, particularly from long-acting oxycodone,which is amore commonlyprescribedopioid than propoxypheneandassociatedwithhigheroverdose risk.3 Less opioidprescribing also likely led to fewer opioids available for diversion (to both beneficiaries andnonbeneficiaries), lowering population risk. Finally, making long-acting oxycodone availableonly inanabuse-deterrent formulationmayhaveprevented divertedmedications from being used parenterally or intranasally—both riskier than oral use. Regardless, making long-actingopioidsexclusivelyavailable inabuse-deterrent formulations, particularly for new medications as they are released to the market, is a structural lever that may minimize adverse public health consequences of long-acting opioids. Abuse-deterrent formulations composeonlypart of apublic health strategy to reduce overdose andmisuse. These formulationswill not prevent people receivinghighdoses of opioids fromoverdosing. It remainspossible tooverdoseby taking oralmedications, evenwhenusing themas directed, particularlywhen incombinationwithotherprescribedor illicitdrugs. Abuse-deterrentmedicationsalsodonotprevent the initial exposure to opioids. Most opioid use carries some risk, and intensity of the exposure via dose and length of treatment increases subsequent risk of misuse and overdose. Related article page 978 Effect of Abuse-Deterrent Oxycodone Introduction and PropoxypheneWithdrawal Original Investigation Research

Buprenorphine infrequently found in fatal overdose in New York City

BACKGROUNDnBuprenorphine is an opioid agonist medication that is both safe and effective in the treatment of opioid use disorders and the prevention of opioid overdoses. Despite this, media coverage has highlighted public concerns about the potential safety consequences of buprenorphine misuse and diversion. To address the possible contribution of buprenorphine to overdose mortality, we systematically tested post mortem blood specimens from decedents who had died of an unintentional drug overdoses in 2013.nnnMETHODSnWe retrospectively tested consecutive drug overdose cases that occurred from June through October 2013. Cases with available blood specimens were tested for buprenorphine and norbuprenorphine using liquid chromatography-tandem mass spectrometry. Toxicology results were linked to death certificates and case files from New York City Vital Statistics and New York City Office of the Chief Medical Examiner.nnnRESULTSnOf the 98 unintentional drug overdose fatalities tested, only 2 (2.0%) tested positive for buprenorphine metabolites. All 98 unintentional fatalities involved multiple substances.nnnCONCLUSIONSnBuprenorphine was infrequently found in drug overdose deaths in New York City. Since the safety and efficacy of buprenorphine are well documented, and overdoses resulting from buprenorphine treatment or diversion are very rare, facilitating access to buprenorphine treatment is strongly recommended.

Naloxone use among overdose prevention trainees in New York City: A longitudinal cohort study

BACKGROUNDnProviding naloxone to laypersons who are likely to witness an opioid overdose is now a widespread public health response to the national opioid overdose epidemic. Estimating the proportion of individuals who use naloxone can define its potential impact to reduce overdose deaths at a population level. We determined the proportion of study participants who used naloxone within 12 months following training and factors associated with witnessing overdose and naloxone use.nnnMETHODSnWe conducted a prospective, observational study of individuals completing overdose prevention training (OPT) between June and September 2013. Participants were recruited from New York Citys six largest overdose prevention programs, all operated by syringe exchange programs. Questionnaires were administered at four time points over 12 months. Main outcomes were witnessing or experiencing overdose, and naloxone administration.nnnRESULTSnOf 675 individuals completing OPT, 429 (64%) were approached and 351 (52%) were enrolled. Overall, 299 (85%) study participants completed at least one follow-up survey; 128 (36%) witnessed at least one overdose. Of 312 witnessed opioid overdoses, naloxone was administered in 241 events (77%); 188 (60%) by the OPT study participant. Eighty-six (25%) study participants administered naloxone at least once. Over one third of study participants (30, 35%) used naloxone 6 or more months after training.nnnCONCLUSIONSnWitnessing an overdose and naloxone use was common among this study cohort of OPT trainees. Training individuals at high risk for witnessing overdoses may reduce opioid overdose mortality at a population level if sufficient numbers of potential responders are equipped with naloxone.

Developing Syndromic Surveillance to Monitor and Respond to Adverse Health Events Related to Psychoactive Substance Use: Methods and Applications.

Introduction: Recent increases in drug overdose deaths, both in New York City and nationally, highlight the need for timely data on psychoactive drug-related morbidity. We developed drug syndrome definitions for syndromic surveillance to monitor drug-related emergency department (ED) visits in real time. Materials and Methods: We used 2012 archived syndromic surveillance data from New York City hospitals to develop definitions for psychoactive drug-related syndromes. The dataset contained ED visit-level information that included patients’ chief complaints, dates of visits, ZIP codes of residence, discharge diagnoses, and dispositions. After manually reviewing chief complaints, we developed a classification scheme comprising 3 categories (overdose, drug mention, and drug abuse/misuse), which we used to define 25 psychoactive drug syndromes. From July 2013 through December 2015, the New York City Department of Health and Mental Hygiene performed daily syndromic surveillance of psychoactive drug-related ED visits using the 25 syndrome definitions. Results: Syndromic surveillance triggered 4 public health investigations, supported 8 other public health investigations that had been triggered by other mechanisms, and resulted in the identification of 5 psychoactive drug-related outbreaks. Syndromic surveillance also identified a substantial increase in synthetic cannabinoid-related visits (from an average of 3 per week in January 2014 to >300 per week in July 2015) and an increase in heroin overdose visits (from 80 to 171 in the first 3 quarters of 2012 and 2014, respectively) in a single neighborhood. Practice Implications: Syndromic surveillance using these novel definitions enabled monitoring of trends in psychoactive drug-related morbidity, initiation and support of public health investigations, and targeting of interventions. Health departments can refine these definitions for their jurisdictions using the described methods and integrate them into existing syndromic surveillance systems.

Witnessed overdoses and naloxone use among visitors to Rikers Island jails trained in overdose rescue

With the opioid overdose mortality rates rising nationally, The New York City Department of Health and Mental Hygiene (NYC DOHMH) has worked to expand overdose rescue training (ORT) and naloxone distribution. This study sought to determine rates of overdose witnessing and naloxone use among overdose rescue-trained visitors to the NYC jails on Rikers Island. We conducted a six-month prospective study of visitors to NYC jails on Rikers Island who received ORT. We collected baseline characteristics of study participants, characteristics of overdose events, and responses to witnessed overdose events, including whether the victim was the incarcerated individual the participant was visiting on the day of training. Bivariate analyses compared baseline characteristics of participants who witnessed overdoses to those who did not, and of participants who used naloxone to those who did not. Overall, we enrolled 283 participants visiting NYCs Rikers Island jails into the study. Six months after enrollment, we reached 226 participants for follow-up by phone. 40 participants witnessed 70 overdose events, and 28 participants reported using naloxone. Of the 70 overdose events, three victims were the incarcerated individuals visited on the day of training; nine additional victims were recently released from jail and/or prison. Visitors to persons incarcerated at Rikers Island witness overdose events and are able to perform overdose rescues with naloxone. This intervention reaches a population that includes not only those recently released, but also other people who experienced overdose.

Knowledge of the 911 Good Samaritan Law and 911-calling behavior of overdose witnesses

ABSTRACT Background: Overdose deaths tripled between 1999 and 2014. Most fatal overdoses are witnessed, offering an opportunity for bystanders to call 911. However, fear of arrest may prevent them from calling authorities. Many states have passed 911 Good Samaritan laws that protects the 911 caller and overdose victim from prosecution for drug possession. Little is known, however, about whether the law affects 911-calling behavior of overdose witnesses. We investigated the relationship between knowledge of a 911 Good Samaritan Law (GSL) and 911-calling behavior of study participants trained in opioid overdose rescue. Methods: We enrolled 351 individuals (n = 351) trained in overdose rescue and educated about the New York State GSL in a prospective longitudinal study. Trained researchers conducted baseline, three, six and 12-month follow-up surveys with study participants to assess participant knowledge of the GSL and responses to witnessed overdoses. Results: At the twelve-month follow-up, participants had witnessed 326 overdoses. In the overdose events where the participant had correct knowledge of the GSL at the time of the event, the odds of a bystander calling 911 were over three times greater than when the witness had incorrect knowledge of the GSL (OR = 3.3, 95% CI, 1.4–7.5). This association remained significant after adjusting for age, gender, race of the witness and overdose setting (AOR = 3.6, 95% CI, 1.4–9.4). Conclusions: To our knowledge, this is the first study to show an association between knowledge of the GSL and 911-calling behavior. Legislation that protects overdose responders along with public awareness of the law may be an effective strategy to increase rates of 911-calling in response to overdose events and decrease overdose-related mortality.

Does drug treatment improve patient quality of life? A pilot study of the outcomes of the quality of life assessment in New York City outpatient and opioid treatment programs

Background The Affordable Care Act and the Medicaid redesign in New York City offer opportunities to explore alternative methods for measuring the effectiveness of behavioral health interventions. Quality of life (QOL) measures have been underutilized in substance use disorders treatment (SUDT). The objective of this study was to determine how a validated QOL instrument could be used in SUDT as a measure of health-related patient outcomes.