The American Journal on Addictions, 23: 257–264, 2014 Copyright © American Academy of Addiction Psychiatry ISSN: 1055-0496 print / 1521-0391 online DOI: 10.1111/j.1521-0391.2014.12091.x
High Levels of Opioid Analgesic Co‐Prescription Among Methadone Maintenance Treatment Clients in British Columbia, Canada: Results from a Population‐Level Retrospective Cohort Study Bohdan Nosyk, PhD,1,2 Benedikt Fischer, PhD,2,3,4 Huiying Sun, PhD,5 David C. Marsh, MD, FRCPC,6 Thomas Kerr, PhD,1,7 Juergen T. Rehm, PhD,4 Aslam H. Anis, PhD5,8 1
BC Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada 3 Centre for Applied Research in Mental Health and Addictions (CARMHA), Vancouver, British Columbia, Canada 4 Social and Epidemiological Research Department, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada 5 Centre for Health Evaluation & Outcome Sciences, Vancouver, British Columbia, Canada 6 Northern Ontario School of Medicine, Sudbury, Ontario, Canada 7 Division of AIDS, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada 8 School of Population & Public Health, University of British Columbia, Vancouver, British Columbia, Canada 2
Background and Objectives: The non‐medical use of prescription opioids (PO) has increased dramatically in North America. Special consideration for PO prescription is required for individuals in methadone maintenance treatment (MMT). Our objective is to describe the prevalence and correlates of PO use among British Columbia (BC) MMT clients from 1996 to 2007. Methods: This study was based on a linked, population‐level medication dispensation database. All individuals receiving 30 days of continuous MMT for opioid dependence were included in the study. Key measurements included the proportion of clients receiving >7 days of a PO other than methadone during MMT from 1996 to 2007. Factors independently associated with PO co‐prescription during MMT were assessed using generalized linear mixed effects regression. Results: 16,248 individuals with 27,919 MMT episodes at least 30 days in duration were identified for the study period. Among them, 5,552 individuals (34.2%) received a total of 290,543 PO co‐ prescriptions during MMT. The majority (74.3%) of all PO dispensations >7 days originated from non‐MMT physicians. The number of PO prescriptions per person‐year nearly doubled between 1996 and 2006, driven by increases in morphine, hydromorphone and oxycodone dispensations. PO co‐prescription was positively associated with female gender, older age, higher levels of medical co‐ morbidity as well as higher MMT dosage, adherence, and retention.
Received January 4, 2013; revised April 22, 2013; accepted June 1, 2013. Grant sponsor: Canadian Institutes of Health Research and the National Institutes of Health/National Institute on Drug Abuse; Grant number: 1‐R01‐DA031727‐01. Address correspondence to: Nosyk, BC Centre for Excellence in HIV/AIDS, 613‐1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6. E‐mail: [email protected].
Conclusion and Scientific Significance: A large proportion of MMT clients in BC received co‐occurring PO prescriptions, often from physicians and pharmacies not delivering MMT. Experimental evidence for the treatment of pain in MMT clients is required to guide clinical practice. (Am J Addict 2014;23:257–264)
INTRODUCTION The non‐medical use of prescription opioids (POs) has increased dramatically in Canada and the US over the past 15 years,1,2 and is higher in North America than elsewhere in the world.3 This increase is most apparent in the US, where there are approximately 2.3 million individuals contending with opioid dependence or abuse, including 1.9 million with PO drug dependence or abuse.4 The prevalence of prescription drug opioid dependence and abuse grew over 25% from 2005 to 2009, and treatment admissions for non‐heroin opioid abuse in the US almost doubled from 2002 to 2007.4–6 In Ontario, Canada, PO‐related treatment admissions rose by 60%, and their prevalence in the total caseload increased from 9.4% to 15.7% from 2004 to 2009.7 Concurrent PO use among opioid‐dependent individuals during methadone maintenance treatment (MMT) is of particular importance given the potential risk of opioid overdose.8 A complicating factor is that chronic pain is common (ranging from 37% to 61%) among opioid dependent 257
individuals receiving MMT.9–12 Canadian best practices guidelines for MMT acknowledge chronic pain as a common comorbidity among MMT clients, and support the concurrent prescription of opioid analgesics for severe pain, with frequent reassessment to ensure adequate dosage of analgesics and linkages with pain clinics if possible.13 Methadone alone, prescribed for opioid dependence, may not provide sufficient pain relief among individuals with heroin dependence unless taken frequently—some suggest every 8–12 hours.14–17 Several studies have suggested that opioid dependent individuals may exhibit hyperalgesia.18–22 Opioid‐ induced hyperalgesia is characterized by a paradoxical response whereby a patient receiving opioids for the treatment of pain could become more sensitive to certain painful stimuli. It is thought to be a phenomenon that could explain loss of opioid efficacy in some patients, and a result of neuroplastic changes in the peripheral and central nervous system.23 The legitimate need for pain medications is counterbalanced by the risk of diversion. A recent study reported increasing ease of availability for a range of POs within a large cohort of drug users in Vancouver, British Columbia between 2006 and 2010.24 While the illicit supply of POs is likely generated from a number of sources, the direct or indirect supply via dispensation from medical sources (eg, pharmacies) is one possibility.25 In Canada, methadone is available in office‐based settings as well as specialized drug treatment centers. Treatment is then typically dispensed in community‐based pharmacies (initially on a daily basis with ingestion directly observed by the pharmacist, with take home doses available once stabilized), or on‐site in some treatment centers. All clients are entering MMT are recommended to be subject to medical and psychological assessment, as well as urine drug screening to determine eligibility. Urine samples are recommended to be taken on a regular basis, however they are not intended to be a basis of discontinuation if illicit opioids are found. Among MMT clients in Ontario, Canada (2003–2010), 18.4% received at least one dispensation for non‐methadone opioids of more than 7 days’ duration, and nearly half (45.8%) originated from non‐MMT prescribers and pharmacies.26 The authors questioned the clinical need for such a high rate of PO co‐prescribing in the study population, and concluded that many such dispensations may be duplicitous. This and other studies have called for increased use of centralized prescription drug monitoring programs as one feasible policy response, in addition to a range of guidelines for better controls on opioid prescribing.2 British Columbia (BC) has the capability for such monitoring through the BC PharmaNet database, yet it is unclear to what extent it is effectively being utilized. While a duplicate prescription form program was implemented in BC in December of 2005, neither the PO‐prescribing physician nor pharmacy is obliged to notify the MMT physician or pharmacy, nor is there any formal mechanism established to do so.27–29 Our objective was to describe the prevalence and correlates of PO dispensation among BC MMT patients using population‐ level drug dispensation data collected from 1996 to 2006. 258
MATERIALS AND METHODS BC PharmaNet Database This study utilized data from the BC PharmaNet database. PharmaNet is the province‐wide network that links all BC pharmacies to a central set of data systems. Every prescription dispensed in BC is entered into PharmaNet.30 PharmaNet was designed to increase patient safety by allowing pharmacists to access up‐to‐the‐minute information about all prescription medications dispensed to individuals anywhere in BC. Individual‐level PharmaNet information is also available to hospital emergency departments and some medical practices, hospitals and mental health facilities. Patient Population The study cohort included all individuals receiving methadone for opioid dependence over an 11‐year period: January 1, 1996 to December 31, 2006. Data fields available included a de‐identified patient ID, date of birth, gender, drug identification number, the date of the prescription (date), the length of the prescription (number of days supplied, or days), drug dosage (quantity), de‐identified prescriber code and pharmacy code, as well as a geographical identifier, aggregated by local health area. Data on hospitalizations (dates and most responsible diagnoses of hospitalizations) throughout the period of study follow‐up through Population Data BC.31 The study was approved by the University of British Columbia/ Providence Health Care Behavioural Research Ethics Board. MMT Episode Definition and Selection MMT episodes were the focal point of our analysis. These were constructed using the service date and days supplied fields; a treatment episode length was calculated as the difference between the last and first days of dispensed medication (episode length ¼ ðdatet1 +dayst1 Þ datet0 ), where t0 is the date of episode initiation and t1 is last date of service) within a period of continuous retention in treatment, where continuous treatment entailed no interruptions in prescribed doses lasting longer than 30 days. In generating estimates of prevalence of PO co‐prescription, we considered all MMT episodes beginning January 1, 1996 (thus including left‐ censored observations) lasting at least 30 days. Efforts were made to correct any misclassification in the dataset in regards to prescribed doses, lengths and dates of prescriptions. Less than 1% of identified errors could not be corrected. Identification and Descriptive Analysis of PO Dispensation A range of POs were identified in the drug dispensation dataset by two co‐authors (D.C.M. and B.F.). Consistent with past methodology,26 an MMT episode was classified as having PO co‐prescription if a PO prescription >7 days was observed within the dates of initiation and conclusion or censorship of the MMT episode. We provide descriptive statistics on the frequency of PO co‐prescription, overall and across MMT episodes of different duration (24 months; strata chosen based on clinical relevance). Further, frequencies of dispensation by drug class, and the frequency with which POs are prescribed by non‐MMT physicians and dispensed from non‐methadone dispensing pharmacies are also presented. To achieve the latter, we used the delimited physician and pharmacy identifiers attached to each dispensation record available in our dataset. These types of prescription and dispensation records were summarized explicitly following prior studies32 given the higher likelihood of inappropriate or non‐medical PO use.33 Doctor shopping (ie, obtaining opioid prescriptions from multiple prescribers) is a way in which opioids may be abused and their use diverted,34 and diversion through family and friends is now the greatest source of illicit opioids in the US.35
Statistical Analysis Repeated MMT episodes were analyzed using Generalized Linear Mixed Models (GLMMs; specified with a binary distribution and logit link function), regressing the probability of PO co‐prescription against the set of covariates described above, in the interest of identifying factors independently associated with PO co‐prescription during MMT. GLMMs take into account within‐subject correlation across repeated MMT episodes, and capture fixed, individual‐level unmeasured confounding.38 All analyses were executed using SAS version 9.2.
Factors Hypothesized to Be Associated With PO Co‐ Prescription We hypothesized that individual demographics, indicators of medical comorbidity, methadone treatment status and indicators of quality of methadone treatment were associated with PO co‐prescription. Age and gender were elicited directly from the PharmaNet database. The Charlson comorbidity index (CCI) is a validated indicator of medical comorbidity36; the CCI was based on most responsible hospital diagnoses in the 6 months prior to MMT episode initiation. Indicators of treatment status and quality of methadone treatment included maximum episodic dose, treatment adherence, episode duration, and episode count. MMT prescriber patient load, previously identified as an independent predictor of MMT episode duration,37 was also considered, as was urban residence (residence in a city with >50,000 individuals) and calendar year of MMT initiation.
Prevalence of PO Co‐Prescription Between January 1, 1996 and December 31, 2006, there were 16,248 individuals with 27,919 MMT episodes at least 30 days in duration. A total of 5,552 patients (5,552/ 16,248 ¼ 34.2%), with 290,543 PO prescriptions were identified. Among the 5,552 patients, 2,357 (42.4%) received two or more PO co‐prescriptions concurrently during MMT. Among the 290,543 prescriptions, 68,509 (23.6%) were >7 days in duration. The frequency and percentage of days POs were dispensed during MMT are presented in Table 1. POs were dispensed in 28.2% of all MMT episodes during the study duration—7.9% of the duration of the episodes in which they were prescribed. These medications were most commonly dispensed during long‐term MMT episodes. Specifically, POs were dispensed in 47.3% of all episodes lasting >24 months. Within these longer‐term treatment episodes, PO dispensation became
RESULTS
TABLE 1. Frequency of PO dispensation during MMT episodes, by episode duration
All MMT episodes MMT episodes 3 months in duration Ever MMT episodes 3–12 months in duration Ever During first 3 months During months 3–12 MMT episodes 12–24 months in duration Ever During first 3 months During months 3–12 During months 12–24 MMT episodes > 24 months in duration Ever During first 3 months During months 3–12 During months 12–24 During months >24
POs dispensed N (%)
% days POs dispensed median (IQR)
7,875 (28.2)
7.9 (2.5, 27.4)
614 (11.9)
35 (17.1, 63.9)
1,823 (19.3) 1,307 (13.9) 1,390 (14.7)
13.9 (5.5, 38.3) 22.2 (11.1, 54.4) 22.2 (8, 61.1)
1,323 647 1,053 781
(28.4) (13.9) (22.6) (16.8)
6.5 21.1 8.7 16.2
(2.7, (8.9, (3.6, (5.5,
20.6) 51.1) 29.8) 50)
4,115 1,584 2,459 2,714 3,381
(47.3) (18.2) (28.3) (31.2) (38.9)
4.6 22.2 9.1 7.7 5.4
(1.6, (8.9, (3.6, (2.7, (1.6,
18.2) 52.2) 31.6) 28.8) 25.1)
Nosyk et al.
May–June 2014
259
FIGURE 1. Number of PO prescriptions per person year in MMT, by opioid medication: British Columbia, 1996–2006.
progressively more common further from the date of initiation —from 18.2% in the first 3 months, to 38.9% after 24 months. Table 1 also presents figures on the duration of PO prescription during MMT (column 3), expressed as the percentage of days during a given timeframe (first 3 months; months 3–12; 12–24; >24). PO co‐prescription tended to be most frequent within the first 3 months of the MMT episode—this was true in short MMT episodes (median 35% of the duration of the MMT episode), as well as MMT episodes of longer duration (MMT episodes 12–24 months in duration: 21.1% of the duration of the initial 3 months; MMT episodes >24 months in duration: 22.2% of the duration of the initial 3 months). Temporal trends in the number of PO prescriptions per person year in MMT were presented in Figure 1. PO co‐ prescription among MMT clients nearly doubled between 1996 and 2006. This increase was nearly entirely a result of increased prescription of oxycodone, morphine, and hydromorphone. PO Co‐Prescription by Prescribing Physician, Pharmacy Table 2 presents data on the frequency of concordance between the MMT prescribing physician and the PO‐ prescribing physician, as stated in the drug dispensation database. The majority (74.3%) of all PO dispensations >7 days during MMT originated from non‐MMT physicians. A smaller proportion of these dispensations originated from pharmacies not involved in MMT (32.5%), and slightly more than one quarter of all PO co‐prescriptions were from neither the physician nor the pharmacy involved in MMT. At the 260
patient‐level, 85.8% of all patients receiving a PO during MMT at some point had a prescription from a non‐MMT physician, 58.1% received POs from a non‐MMT pharmacy, and 53.1% had at least one PO co‐prescription from neither the physician nor the pharmacy involved in MMT. Factors Associated With PO Co‐Prescription Finally, results of the multivariate analysis assessing factors associated with PO use during MMT are presented in Table 3. We excluded left‐censored (ongoing at treatment initiation) episodes for these analyses, leaving N ¼ 26,393 episodes TABLE 2. Source of non‐methadone opioids prescriptions of duration >7 days
Non‐methadone prescriptions Total number of all non‐methadone opioid prescriptions Non‐MMT physician Non‐MMT pharmacy Non‐MMT physician and Non‐MMT pharmacy Patients receiving non‐methadone opioid Any non‐MMT physician Any non‐MMT pharmacy Any non‐MMT‐physician and non‐MMT pharmacy
PO Co‐Prescription Among MMT Clients in BC, Canada
May–June 2014
68,509 50,911 (74.3%) 22,285 (32.5%) 18,981 (27.7%) 5,552 4,764 (85.8%) 3,326 (58.1%) 2,950 (53.1%)
TABLE 3. Multivariate analysis on factors associated with PO prescription
Female Age 60 CCI score ¼ 0 CCI score ¼ 1–5 CCI score > 6 Maximum daily dosage 120 mg Treatment adherence >90% 70–90% 6th episode Patient load 1st quartile 2nd quartile 3rd quartile 4th quartile Urban Calendar year of episode initiation
Prescribed POs (N ¼ 7,227)
AOR
N (%)
1.424
95% CI
p‐value
1.313
1.545
High Levels of Opioid Analgesic Co‐Prescription Among Methadone Maintenance Treatment Clients in British Columbia, Canada: Results from a Population‐Level Retrospective Cohort Study Bohdan Nosyk, PhD,1,2 Benedikt Fischer, PhD,2,3,4 Huiying Sun, PhD,5 David C. Marsh, MD, FRCPC,6 Thomas Kerr, PhD,1,7 Juergen T. Rehm, PhD,4 Aslam H. Anis, PhD5,8 1
BC Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada 3 Centre for Applied Research in Mental Health and Addictions (CARMHA), Vancouver, British Columbia, Canada 4 Social and Epidemiological Research Department, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada 5 Centre for Health Evaluation & Outcome Sciences, Vancouver, British Columbia, Canada 6 Northern Ontario School of Medicine, Sudbury, Ontario, Canada 7 Division of AIDS, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada 8 School of Population & Public Health, University of British Columbia, Vancouver, British Columbia, Canada 2
Background and Objectives: The non‐medical use of prescription opioids (PO) has increased dramatically in North America. Special consideration for PO prescription is required for individuals in methadone maintenance treatment (MMT). Our objective is to describe the prevalence and correlates of PO use among British Columbia (BC) MMT clients from 1996 to 2007. Methods: This study was based on a linked, population‐level medication dispensation database. All individuals receiving 30 days of continuous MMT for opioid dependence were included in the study. Key measurements included the proportion of clients receiving >7 days of a PO other than methadone during MMT from 1996 to 2007. Factors independently associated with PO co‐prescription during MMT were assessed using generalized linear mixed effects regression. Results: 16,248 individuals with 27,919 MMT episodes at least 30 days in duration were identified for the study period. Among them, 5,552 individuals (34.2%) received a total of 290,543 PO co‐ prescriptions during MMT. The majority (74.3%) of all PO dispensations >7 days originated from non‐MMT physicians. The number of PO prescriptions per person‐year nearly doubled between 1996 and 2006, driven by increases in morphine, hydromorphone and oxycodone dispensations. PO co‐prescription was positively associated with female gender, older age, higher levels of medical co‐ morbidity as well as higher MMT dosage, adherence, and retention.
Received January 4, 2013; revised April 22, 2013; accepted June 1, 2013. Grant sponsor: Canadian Institutes of Health Research and the National Institutes of Health/National Institute on Drug Abuse; Grant number: 1‐R01‐DA031727‐01. Address correspondence to: Nosyk, BC Centre for Excellence in HIV/AIDS, 613‐1081 Burrard Street, Vancouver, BC, Canada V6Z 1Y6. E‐mail: [email protected].
Conclusion and Scientific Significance: A large proportion of MMT clients in BC received co‐occurring PO prescriptions, often from physicians and pharmacies not delivering MMT. Experimental evidence for the treatment of pain in MMT clients is required to guide clinical practice. (Am J Addict 2014;23:257–264)
INTRODUCTION The non‐medical use of prescription opioids (POs) has increased dramatically in Canada and the US over the past 15 years,1,2 and is higher in North America than elsewhere in the world.3 This increase is most apparent in the US, where there are approximately 2.3 million individuals contending with opioid dependence or abuse, including 1.9 million with PO drug dependence or abuse.4 The prevalence of prescription drug opioid dependence and abuse grew over 25% from 2005 to 2009, and treatment admissions for non‐heroin opioid abuse in the US almost doubled from 2002 to 2007.4–6 In Ontario, Canada, PO‐related treatment admissions rose by 60%, and their prevalence in the total caseload increased from 9.4% to 15.7% from 2004 to 2009.7 Concurrent PO use among opioid‐dependent individuals during methadone maintenance treatment (MMT) is of particular importance given the potential risk of opioid overdose.8 A complicating factor is that chronic pain is common (ranging from 37% to 61%) among opioid dependent 257
individuals receiving MMT.9–12 Canadian best practices guidelines for MMT acknowledge chronic pain as a common comorbidity among MMT clients, and support the concurrent prescription of opioid analgesics for severe pain, with frequent reassessment to ensure adequate dosage of analgesics and linkages with pain clinics if possible.13 Methadone alone, prescribed for opioid dependence, may not provide sufficient pain relief among individuals with heroin dependence unless taken frequently—some suggest every 8–12 hours.14–17 Several studies have suggested that opioid dependent individuals may exhibit hyperalgesia.18–22 Opioid‐ induced hyperalgesia is characterized by a paradoxical response whereby a patient receiving opioids for the treatment of pain could become more sensitive to certain painful stimuli. It is thought to be a phenomenon that could explain loss of opioid efficacy in some patients, and a result of neuroplastic changes in the peripheral and central nervous system.23 The legitimate need for pain medications is counterbalanced by the risk of diversion. A recent study reported increasing ease of availability for a range of POs within a large cohort of drug users in Vancouver, British Columbia between 2006 and 2010.24 While the illicit supply of POs is likely generated from a number of sources, the direct or indirect supply via dispensation from medical sources (eg, pharmacies) is one possibility.25 In Canada, methadone is available in office‐based settings as well as specialized drug treatment centers. Treatment is then typically dispensed in community‐based pharmacies (initially on a daily basis with ingestion directly observed by the pharmacist, with take home doses available once stabilized), or on‐site in some treatment centers. All clients are entering MMT are recommended to be subject to medical and psychological assessment, as well as urine drug screening to determine eligibility. Urine samples are recommended to be taken on a regular basis, however they are not intended to be a basis of discontinuation if illicit opioids are found. Among MMT clients in Ontario, Canada (2003–2010), 18.4% received at least one dispensation for non‐methadone opioids of more than 7 days’ duration, and nearly half (45.8%) originated from non‐MMT prescribers and pharmacies.26 The authors questioned the clinical need for such a high rate of PO co‐prescribing in the study population, and concluded that many such dispensations may be duplicitous. This and other studies have called for increased use of centralized prescription drug monitoring programs as one feasible policy response, in addition to a range of guidelines for better controls on opioid prescribing.2 British Columbia (BC) has the capability for such monitoring through the BC PharmaNet database, yet it is unclear to what extent it is effectively being utilized. While a duplicate prescription form program was implemented in BC in December of 2005, neither the PO‐prescribing physician nor pharmacy is obliged to notify the MMT physician or pharmacy, nor is there any formal mechanism established to do so.27–29 Our objective was to describe the prevalence and correlates of PO dispensation among BC MMT patients using population‐ level drug dispensation data collected from 1996 to 2006. 258
MATERIALS AND METHODS BC PharmaNet Database This study utilized data from the BC PharmaNet database. PharmaNet is the province‐wide network that links all BC pharmacies to a central set of data systems. Every prescription dispensed in BC is entered into PharmaNet.30 PharmaNet was designed to increase patient safety by allowing pharmacists to access up‐to‐the‐minute information about all prescription medications dispensed to individuals anywhere in BC. Individual‐level PharmaNet information is also available to hospital emergency departments and some medical practices, hospitals and mental health facilities. Patient Population The study cohort included all individuals receiving methadone for opioid dependence over an 11‐year period: January 1, 1996 to December 31, 2006. Data fields available included a de‐identified patient ID, date of birth, gender, drug identification number, the date of the prescription (date), the length of the prescription (number of days supplied, or days), drug dosage (quantity), de‐identified prescriber code and pharmacy code, as well as a geographical identifier, aggregated by local health area. Data on hospitalizations (dates and most responsible diagnoses of hospitalizations) throughout the period of study follow‐up through Population Data BC.31 The study was approved by the University of British Columbia/ Providence Health Care Behavioural Research Ethics Board. MMT Episode Definition and Selection MMT episodes were the focal point of our analysis. These were constructed using the service date and days supplied fields; a treatment episode length was calculated as the difference between the last and first days of dispensed medication (episode length ¼ ðdatet1 +dayst1 Þ datet0 ), where t0 is the date of episode initiation and t1 is last date of service) within a period of continuous retention in treatment, where continuous treatment entailed no interruptions in prescribed doses lasting longer than 30 days. In generating estimates of prevalence of PO co‐prescription, we considered all MMT episodes beginning January 1, 1996 (thus including left‐ censored observations) lasting at least 30 days. Efforts were made to correct any misclassification in the dataset in regards to prescribed doses, lengths and dates of prescriptions. Less than 1% of identified errors could not be corrected. Identification and Descriptive Analysis of PO Dispensation A range of POs were identified in the drug dispensation dataset by two co‐authors (D.C.M. and B.F.). Consistent with past methodology,26 an MMT episode was classified as having PO co‐prescription if a PO prescription >7 days was observed within the dates of initiation and conclusion or censorship of the MMT episode. We provide descriptive statistics on the frequency of PO co‐prescription, overall and across MMT episodes of different duration (24 months; strata chosen based on clinical relevance). Further, frequencies of dispensation by drug class, and the frequency with which POs are prescribed by non‐MMT physicians and dispensed from non‐methadone dispensing pharmacies are also presented. To achieve the latter, we used the delimited physician and pharmacy identifiers attached to each dispensation record available in our dataset. These types of prescription and dispensation records were summarized explicitly following prior studies32 given the higher likelihood of inappropriate or non‐medical PO use.33 Doctor shopping (ie, obtaining opioid prescriptions from multiple prescribers) is a way in which opioids may be abused and their use diverted,34 and diversion through family and friends is now the greatest source of illicit opioids in the US.35
Statistical Analysis Repeated MMT episodes were analyzed using Generalized Linear Mixed Models (GLMMs; specified with a binary distribution and logit link function), regressing the probability of PO co‐prescription against the set of covariates described above, in the interest of identifying factors independently associated with PO co‐prescription during MMT. GLMMs take into account within‐subject correlation across repeated MMT episodes, and capture fixed, individual‐level unmeasured confounding.38 All analyses were executed using SAS version 9.2.
Factors Hypothesized to Be Associated With PO Co‐ Prescription We hypothesized that individual demographics, indicators of medical comorbidity, methadone treatment status and indicators of quality of methadone treatment were associated with PO co‐prescription. Age and gender were elicited directly from the PharmaNet database. The Charlson comorbidity index (CCI) is a validated indicator of medical comorbidity36; the CCI was based on most responsible hospital diagnoses in the 6 months prior to MMT episode initiation. Indicators of treatment status and quality of methadone treatment included maximum episodic dose, treatment adherence, episode duration, and episode count. MMT prescriber patient load, previously identified as an independent predictor of MMT episode duration,37 was also considered, as was urban residence (residence in a city with >50,000 individuals) and calendar year of MMT initiation.
Prevalence of PO Co‐Prescription Between January 1, 1996 and December 31, 2006, there were 16,248 individuals with 27,919 MMT episodes at least 30 days in duration. A total of 5,552 patients (5,552/ 16,248 ¼ 34.2%), with 290,543 PO prescriptions were identified. Among the 5,552 patients, 2,357 (42.4%) received two or more PO co‐prescriptions concurrently during MMT. Among the 290,543 prescriptions, 68,509 (23.6%) were >7 days in duration. The frequency and percentage of days POs were dispensed during MMT are presented in Table 1. POs were dispensed in 28.2% of all MMT episodes during the study duration—7.9% of the duration of the episodes in which they were prescribed. These medications were most commonly dispensed during long‐term MMT episodes. Specifically, POs were dispensed in 47.3% of all episodes lasting >24 months. Within these longer‐term treatment episodes, PO dispensation became
RESULTS
TABLE 1. Frequency of PO dispensation during MMT episodes, by episode duration
All MMT episodes MMT episodes 3 months in duration Ever MMT episodes 3–12 months in duration Ever During first 3 months During months 3–12 MMT episodes 12–24 months in duration Ever During first 3 months During months 3–12 During months 12–24 MMT episodes > 24 months in duration Ever During first 3 months During months 3–12 During months 12–24 During months >24
POs dispensed N (%)
% days POs dispensed median (IQR)
7,875 (28.2)
7.9 (2.5, 27.4)
614 (11.9)
35 (17.1, 63.9)
1,823 (19.3) 1,307 (13.9) 1,390 (14.7)
13.9 (5.5, 38.3) 22.2 (11.1, 54.4) 22.2 (8, 61.1)
1,323 647 1,053 781
(28.4) (13.9) (22.6) (16.8)
6.5 21.1 8.7 16.2
(2.7, (8.9, (3.6, (5.5,
20.6) 51.1) 29.8) 50)
4,115 1,584 2,459 2,714 3,381
(47.3) (18.2) (28.3) (31.2) (38.9)
4.6 22.2 9.1 7.7 5.4
(1.6, (8.9, (3.6, (2.7, (1.6,
18.2) 52.2) 31.6) 28.8) 25.1)
Nosyk et al.
May–June 2014
259
FIGURE 1. Number of PO prescriptions per person year in MMT, by opioid medication: British Columbia, 1996–2006.
progressively more common further from the date of initiation —from 18.2% in the first 3 months, to 38.9% after 24 months. Table 1 also presents figures on the duration of PO prescription during MMT (column 3), expressed as the percentage of days during a given timeframe (first 3 months; months 3–12; 12–24; >24). PO co‐prescription tended to be most frequent within the first 3 months of the MMT episode—this was true in short MMT episodes (median 35% of the duration of the MMT episode), as well as MMT episodes of longer duration (MMT episodes 12–24 months in duration: 21.1% of the duration of the initial 3 months; MMT episodes >24 months in duration: 22.2% of the duration of the initial 3 months). Temporal trends in the number of PO prescriptions per person year in MMT were presented in Figure 1. PO co‐ prescription among MMT clients nearly doubled between 1996 and 2006. This increase was nearly entirely a result of increased prescription of oxycodone, morphine, and hydromorphone. PO Co‐Prescription by Prescribing Physician, Pharmacy Table 2 presents data on the frequency of concordance between the MMT prescribing physician and the PO‐ prescribing physician, as stated in the drug dispensation database. The majority (74.3%) of all PO dispensations >7 days during MMT originated from non‐MMT physicians. A smaller proportion of these dispensations originated from pharmacies not involved in MMT (32.5%), and slightly more than one quarter of all PO co‐prescriptions were from neither the physician nor the pharmacy involved in MMT. At the 260
patient‐level, 85.8% of all patients receiving a PO during MMT at some point had a prescription from a non‐MMT physician, 58.1% received POs from a non‐MMT pharmacy, and 53.1% had at least one PO co‐prescription from neither the physician nor the pharmacy involved in MMT. Factors Associated With PO Co‐Prescription Finally, results of the multivariate analysis assessing factors associated with PO use during MMT are presented in Table 3. We excluded left‐censored (ongoing at treatment initiation) episodes for these analyses, leaving N ¼ 26,393 episodes TABLE 2. Source of non‐methadone opioids prescriptions of duration >7 days
Non‐methadone prescriptions Total number of all non‐methadone opioid prescriptions Non‐MMT physician Non‐MMT pharmacy Non‐MMT physician and Non‐MMT pharmacy Patients receiving non‐methadone opioid Any non‐MMT physician Any non‐MMT pharmacy Any non‐MMT‐physician and non‐MMT pharmacy
PO Co‐Prescription Among MMT Clients in BC, Canada
May–June 2014
68,509 50,911 (74.3%) 22,285 (32.5%) 18,981 (27.7%) 5,552 4,764 (85.8%) 3,326 (58.1%) 2,950 (53.1%)
TABLE 3. Multivariate analysis on factors associated with PO prescription
Female Age 60 CCI score ¼ 0 CCI score ¼ 1–5 CCI score > 6 Maximum daily dosage 120 mg Treatment adherence >90% 70–90% 6th episode Patient load 1st quartile 2nd quartile 3rd quartile 4th quartile Urban Calendar year of episode initiation
Prescribed POs (N ¼ 7,227)
AOR
N (%)
1.424
95% CI
p‐value
1.313
1.545
