Short-acting and Long-acting Opioids Utilization among Women Diagnosed with Endometriosis in the United States: A Population-based Claims Study.

STUDY OBJECTIVE: To determine the prevalence and pattern of opioid use in endometriosis and the characteristics of patients prescribed an opioid using medical insurance claims data. DESIGN: We performed a retrospective cohort analysis of data from the Truven MarketScan Commercial database for the period of January 1, 2011 to December 31, 2016. SETTING: The Truven database includes inpatient, outpatient, and prescription claims covering more than 115 million unique individuals and over 36 million inpatient hospital discharges across multiple payer types and all 50 states. PATIENTS: Women with endometriosis were defined as those with 1 inpatient or 2 outpatient codes for endometriosis. INTERVENTIONS: No interventions were assigned. Women who filled an opioid prescription within 12 months of diagnosis were placed in the opioid cohort and women who did not fill an opioid prescription were placed in the nonopioid cohort. MEASUREMENTS AND MAIN RESULTS: Baseline characteristics were evaluated 12 months preindex (date of the first diagnosis) and opioid use was assessed for 12 months after the index date. The dataset included 58 472 women with endometriosis. Of these, 61.7% filled an opioid prescription during the study period. More than 95% filled prescriptions for short-acting opioids (SAOs) only, 4.1% filled prescriptions for both SAOs and extended-release/long-acting opioids (LAOs), and 0.6% filled prescriptions for LAOs only. Patients who filled an opioid prescription had higher baseline comorbidities (especially gynecologic and chronic pain comorbidities) and endometriosis-related medication use compared with patients who did not fill an opioid prescription during the study period. Patients who filled both LAO and SAO prescriptions had the highest total days' supply of opioids, the proportion of days covered by prescriptions, and morphine equivalent daily dose. These patients also had the highest proportions of opioid switching and dose augmentation. Statistical trends in data were not substantially altered when analyses excluded patients with chronic pain comorbidities or surgical opioid prescriptions. CONCLUSION: Although opioids are not a recommended treatment for endometriosis, more than half of our cohort filled an opioid prescription within 1 year after a first recorded diagnosis of endometriosis. Patients who filled an opioid prescription tended to use more endometriosis-related medications and have a higher comorbidity burden. Additional research is necessary to better understand the reasons and outcomes associated with opioid utilization in endometriosis and to determine if there is a more effective pain management treatment plan for patients taking opioids.

Opioids Prescribed at Discharge or Given During Emergency Department Visits Among Adults in the United States, 2016.

Opioid analgesics are primarily used to treat chronic and acute pain and, when used appropriately, can be an important part of treatment (1). Pain is a major symptom of patients visiting the emergency department (ED), with up to 42% of ED visits being related to pain (2). Opioids may either be administered in the ED as part of treatment, provided post-treatment in the form of a prescription, or both (3). This report compares rates and percentages of ED visits by adults at which opioids were only given in the ED, only prescribed at discharge, or both, by selected characteristics.

Assessment of Changes in the Geographical Distribution of Opioid-Related Mortality Across the United States by Opioid Type, 1999-2016.

Importance: As the opioid epidemic evolves, it is vital to identify changes in the geographical distribution of opioid-related deaths, and the specific opioids to which those deaths are attributed, to ensure that federal and state public health interventions remain appropriately targeted. Objective: To identify changes in the geographical distribution of opioid-related mortality across the United States by opioid type. Design, Setting, and Participants: Cross-sectional study using joinpoint modeling and life table analysis of individual-level data from the National Center for Health Statistics on 351 630 US residents who died from opioid-related causes from January 1, 1999, to December 31, 2016, for all of the United States and the District of Columbia. The analysis was conducted from September 6 to November 23, 2018. Exposures: Deaths involving any opioid, heroin, synthetic opioids, and natural and semisynthetic opioids. Main Outcomes and Measures: Opioid-related mortality rate, annual percent change in the opioid-related mortality rate, and life expectancy lost at age 15 years by state and opioid type. Results: From 1999 to 2016, a total of 231 264 men and 120 366 women died from opioid-related causes across the whole United States. Sixty-six observations were removed owing to missing data on age; therefore, 351 564 US residents were included in this study. The mean (SD) age at death was 39.8 (12.5) years for men and was 43.5 (12.9) years from women. Opioid-related mortality rates, especially from synthetic opioids, rapidly increased in all of the eastern United States. In most states, mortality associated with natural and semisynthetic opioids (ie, prescription painkillers) remained stable. In contrast, 28 states had mortality rates from synthetic opioids that more than doubled every 2 years (ie, annual percent change, ≥41%), including 12 with high mortality rates from synthetic opioids (>10 per 100 000 people). Among these 28 states, the mortality rate from natural and semisynthetic opioids ranged from 2.0 to 18.7 per 100 000 people (with a mean mortality rate of 6.0 per 100 000 people). The District of Columbia had the fastest rate of increase in mortality from opioids, more than tripling every year since 2013 (annual percent change, 228.3%; 95% CI, 169.7%-299.6%; P < .001), and a high mortality rate from synthetic opioids in 2016 (18.8 per 100 000 people); the mortality rate from natural and semisynthetic opioids was 6.9 per 100 000 people. Nationally, overall opioid-related mortality resulted in 0.36 years of life expectancy lost in 2016, which was 14% higher than deaths due to firearms and 18% higher than deaths due to motor vehicle crashes; 0.17 years of the life expectancy lost was due specifically to synthetic opioids. In 2016, New Hampshire and West Virginia lost more than 1 year of life expectancy due to opioid-related mortality. Conclusions and Relevance: Opioid-related mortality, particularly mortality associated with synthetic opioids, has increased in the eastern United States. These findings indicate that policies focused on reducing opioid-related deaths may need to prioritize synthetic opioids and rapidly expanding epidemics in northeastern states and consider the potential for synthetic opioid epidemics outside of the heroin supply.

The Effect of a Federal Controlled Substance Act Schedule Change on Hydrocodone Combination Products Claims in a Medicaid Population.

BACKGROUND: In 2012, hydrocodone combination products (HCPs) were the most prescribed medications in the United States. Under the Controlled Substance Act of 1970, hydrocodone alone was classified as a Schedule II drug, while HCPs were classified as Schedule III, indicating a lower risk for abuse and misuse. However, according to a Drug Enforcement Agency analysis, the addition of nonopioids has not been shown to diminish abuse potential of hydrocodone. In response to concerns for drug abuse and overdose, the Drug Enforcement Agency rescheduled HCPs to Schedule II in October 2014, with the intent of limiting overprescribing and increasing awareness of their abuse potential. However, it is unknown whether this has affected the overall claims for HCPs in a Medicaid population. OBJECTIVES: To (a) compare the trend in HCP prescription claims with select non-HCP (opioid and nonopioid) analgesic claims before and after the HCP schedule change in the Massachusetts Medicaid fee-for-service/Primary Care Clinician plan population and (b) identify if there was a change in HCP new start member and claim characteristics before and after the HCP schedule change. METHODS: This quasi-experimental, retrospective study used enrollment and pharmacy claims data to evaluate all members in the study population 1 year before and after the HCP schedule change. The number of claims for HCPs and select non-HCP analgesics was reported as the monthly rate per total population, and an interrupted time series analysis compared the change in the monthly rate of claims across groups. Members with 1 or more pharmacy claims for a new HCP prescription during a 5-month period before or after the HCP schedule change were analyzed to determine member demographics (age, gender, and number of claims) and claim characteristics (average daily dose, average quantity per claim, and days supply). RESULTS: The rate of HCP claims increased before and decreased after the HCP schedule change. Controlling for the trend during the period before the HCP schedule change, the rate of HCP claims per 1,000 members per month decreased at a greater rate than non-HCP analgesics in the period after the HCP schedule change (P < 0.001). The percentage of HCP claims for new start members decreased after the HCP schedule change (44.9% vs. 34.1% of all HCP claims pre- to post-schedule change; P < 0.001). In the group of new starts, there was not a significant difference in the average daily dose (26.3 mg vs. 26.4 mg; P = 0.69), while there was a decrease in average number of tablets dispensed per claim (from 37.1 to 20.3 tablets; P < 0.001) and an increase in the percentage of claims for a shorter days supply (from 57.7% to 81.6%; P < 0.001). CONCLUSIONS: The findings of this study suggest that the HCP schedule change may have contributed to the decrease in claims for HCPs in a Medicaid population. After the HCP schedule change, there was a trend towards decreased HCP use among new starts. DISCLOSURES: No outside funding supported this study. The authors have nothing to disclose. Study concept and design were contributed by all authors except for Arnold and Clements. Tran, Arnold, and Clements took the lead in data collection, along with Peristere, and data interpretation was performed by all the authors, except Arnold. The manuscript was written primarily by Tran, along with Lavitas, Stevens, and Greenwood, and revised by all the authors except Arnold and Peristere. A poster of this research project was presented at the Academy of Managed Care Pharmacy's 2016 Annual Meeting in San Francisco, California, April 2016.

Trends in high-dose opioid prescribing in Canada.

OBJECTIVE: To describe trends in rates of prescribing of high-dose opioid formulations and variations in opioid product selection across Canada. DESIGN: Population-based, cross-sectional study. SETTING: Canada. PARTICIPANTS: Retail pharmacies dispensing opioids between January 1, 2006, and December 31, 2011. MAIN OUTCOME MEASURES: Opioid dispensing rates, reported as the number of units dispensed per 1000 population, stratified by province and opioid type. RESULTS: The rate of dispensing high-dose opioid formulations increased 23.0%, from 781 units per 1000 population in 2006 to 961 units per 1000 population in 2011. Although these rates remained relatively stable in Alberta (6.3% increase) and British Columbia (8.4% increase), rates in Newfoundland and Labrador (84.7% increase) and Saskatchewan (54.0% increase) rose substantially. Ontario exhibited the highest annual rate of high-dose oxycodone and fentanyl dispensing (756 tablets and 112 patches per 1000 population, respectively), while Alberta's rate of high-dose morphine dispensing was the highest in Canada (347 units per 1000 population). Two of the highest rates of high-dose hydromorphone dispensing were found in Saskatchewan and Nova Scotia (258 and 369 units per 1000 population, respectively). Conversely, Quebec had the lowest rate of high-dose oxycodone and morphine dispensing (98 and 53 units per 1000 population, respectively). CONCLUSION: We found marked interprovincial variation in the dispensing of high-dose opioid formulations in Canada, emphasizing the need to understand the reasons for these differences, and to consider developing a national strategy to address opioid prescribing.

Prescriptions for schedule II opioids and benzodiazepines increase after the introduction of computer-generated prescriptions.

BACKGROUND: Prescriptions for controlled substances decrease when regulatory barriers are put in place. The converse has not been studied. OBJECTIVES: The objective was to determine whether a less complicated prescription writing process is associated with a change in the prescribing patterns of controlled substances in the emergency department (ED). METHODS: The authors conducted a retrospective nonconcurrent cohort study of all patients seen in an adult ED between April 19, 2005, and April 18, 2007, who were discharged with a prescription. Prior to April 19, 2006, a specialized prescription form stored in a locked cabinet was obtained from the nursing staff to write a prescription for benzodiazepines or Schedule II opioids. After April 19, 2006, New York State mandated that all prescriptions, regardless of schedule classification, be generated on a specialized bar-coded prescription form. The main outcome of the study was to compare the proportion of Schedule III-V opioids to Schedule II opioids and benzodiazepines prescribed in the ED before and after the introduction of a less cumbersome prescription writing process. RESULTS: Of the 26,638 charts reviewed, 2.1% of the total number of prescriptions generated were for a Schedule II controlled opioid before the new system was implemented compared to 13.6% after (odds ratio [OR] = 7.3, 95% confidence interval [CI] = 6.4 to 8.4). The corresponding percentages for Schedule III-V opioids were 29.9% to 18.1% (OR = 0.52, 95% CI = 0.49 to 0.55) and for benzodiazepines 1.4% to 3.9% (OR = 2.8, 95% CI = 2.4 to 3.4). CONCLUSIONS: Patients were more likely to receive a prescription for a Schedule II opioid or a benzodiazepine after a more streamlined computer-generated prescription writing process was introduced in this ED.

Internet surveillance: content analysis and monitoring of product-specific internet prescription opioid abuse-related postings.

OBJECTIVES: This study describes the development of a systematic approach to the analysis of Internet chatter as a means of monitoring potentially abusable opioid analgesics. METHODS: Message boards dedicated to drug abuse were selected using specific inclusion criteria. Threaded discussions containing 48,293 posts were captured. A coding system was created to compare content of posts related to 3 opioid analgesics: Kadian, Vicodin, and OxyContin. RESULTS: The number of posts containing mentions of the target drugs were significantly different [OxyContin (1813)>Vicodin (940)>Kadian (27), P<0.001]. Analyses revealed that these differences were not simply a reflection of the availability of each product (ie, number of prescriptions written). Reliability tests indicated that the content coding system achieved good interrater reliability coefficients (average kappa across all categories=0.76, range=0.52 to 1.0). Content analysis of a sample of 234 randomly selected posts indicated that the proportion of Internet posts endorsing abuse of Kadian was statistically significantly less than OxyContin (45.5% vs. 68.4%, P=0.036, not adjusted for multiple comparisons). DISCUSSION: These results suggest that a systematic approach to postmarketing surveillance of Internet chatter related to pharmaceutical products is feasible and yields reliable information about the quantity of discussion of specific products and qualitative information regarding the nature of the discussions. Kadian was associated with fewer Internet mentions than either OxyContin or Vicodin. This investigation stands as a first attempt to establish systematic methods for conducting Internet surveillance.

Geographic variation in the prescription of schedule II opioid analgesics among outpatients in the United States.

OBJECTIVE: To measure geographic variation in opioid use in a large, commercially insured, outpatient population in the United States. DATA SOURCES: Outpatient prescription drug claims database of a national pharmaceutical benefit manager for 7,873,337 subjects with at least one prescription drug claim in 2000. STUDY DESIGN: We measured the period prevalence of claims for opioid analgesics and controlled-release oxycodone at the state level. We measured geographic variation using the weighted coefficient of variation and systematic component of variation. In county-level multivariable regression, we explored associations between potential explanatory variables and claims for opioid analgesics and controlled-release oxycodone. PRINCIPAL FINDINGS: A total of 567,778 (64.2 per 1,000 total claims) were for oral opioid analgesics. Claim rates by state ranged from <20 to >100 claims per 1,000 total claims. States with long-standing prescription monitoring programs had among the lowest rates. In the county-level data, presence of a statewide prescription monitoring program and proportions of the population aged 15-24 and 65 years and older were independently and negatively associated with claim rates for all opioid analgesics. Surgeons per 1,000, proportion of the population reporting illicit drug use, and proportion who were female were independently and positively associated with claim rates for all opioid analgesics. Only the proportion of the population aged 25-34 and number of surgeons per 1,000 were independently and positively associated with claim rates for oxycodone. CONCLUSIONS: Claim rates for opioid analgesics vary significantly by state. Presence of a statewide prescription monitoring program is associated with lower claim rates at the county level. Future research should use individual-level data to assess whether these findings reflect a reduction in abuse and diversion or suboptimal treatment of pain.

Opioid dosing trends and mortality in Washington State workers' compensation, 1996-2002.

BACKGROUND: The use of opioids for chronic non-cancer pain has increased in the United States since state laws were relaxed in the late 1990s. These policy changes occurred despite scanty scientific evidence that chronic use of opioids was safe and effective. METHODS: We examined opiate prescriptions and dosing patterns (from computerized databases, 1996 to 2002), and accidental poisoning deaths attributable to opioid use (from death certificates, 1995 to 2002), in the Washington State workers' compensation system. RESULTS: Opioid prescriptions increased only modestly between 1996 and 2002. However, prescriptions for the most potent opioids (Schedule II), as a percentage of all scheduled opioid prescriptions (II, III, and IV), increased from 19.3% in 1996 to 37.2% in 2002. Among long-acting opioids, the average daily morphine equivalent dose increased by 50%, to 132 mg/day. Thirty-two deaths were definitely or probably related to accidental overdose of opioids. The majority of deaths involved men (84%) and smokers (69%). CONCLUSIONS: The reasons for escalating doses of the most potent opioids are unknown, but it is possible that tolerance or opioid-induced abnormal pain sensitivity may be occurring in some workers who use opioids for chronic pain. Opioid-related deaths in this population may be preventable through use of prudent guidelines regarding opioid use for chronic pain.

Navigating the waters of pharmacy regulations in hospice care. Facing a common scenario: why can it be so difficult to obtain emergency medications?

Imagine a common scenario that faces many hospice clinicians: It is 1 a.m., and the sister of your newest patient just called the on-call service to alert your hospice that the patient is in excruciating pain. In fact, the patient's pain is so bad that she is asking whether she should take her to the nearest hospital emergency room. You anticipated this pain, of course, but the patient did not have moderate or severe pain to this point, and the physician wouldn't agree to provide a small supply of morphine to have on hand.

Potent analgesics are more expensive for patients in developing countries: a comparative study.

Opioids are some of the most important analgesic medications for the management of both moderate to severe pain and several are included on the World Health organization (WHO) list of essential drugs. Opioid costs in developing countries have been reported to be higher than those in developed nations. This study documents retail prices and availability of several potent opioids in a number of developing and developed countries. Pain and Palliative Care specialists currently working in their countries were asked to collect data on the retail cost of a 30 day supply of 15 different opioid preparations in 5 developing and 7 developed countries. Data were analyzed to compare costs and costs as a percentage of gross national product (GNP) per capita per month. Opioid costs and availability varied widely in both developing and developed countries. Forty five of 75 opioid preparations were available in developing countries (40% of medications studied were not available) and 76 of 105 preparations were available in the developed countries (28% not available). In US dollars, the median cost of opioids differed between developed and developing countries ($53 and $112 respectively) The median costs of all opioid preparations as a percentage of GNP per capita per month were 36% for developing and 3% for developed nations; the difference was statistically significant (p < 0.001). In developing countries 23 of 45 (51%) of opioid dosage forms cost more than 30% of the monthly GNP per capita, versus only three of 76 (4%) in developed countries. The relative cost of opioids to income is higher in developing countries. Our data suggest that in developing countries opioid access for the majority of patients is likely to be limited by cost, and development of palliative care programs will require heavy or total subsidization of opioid costs.