Prevalence and duration of prescribed opioid use during pregnancy: a cohort study from the Quebec Pregnancy Cohort

Background Recent studies show a rapid growth among pregnant women using high potency opioids for common pain management during their pregnancy. No study has examined the duration of treatment among strong opioid users and weak opioid users during pregnancy. We aimed to investigate the prevalence of prescribed opioid use during pregnancy, in Quebec; and to compare the duration of opioid treatment between strong opioid users and weak opioid users. Methods Using the Quebec Pregnancy Cohort (1998–2015), we included all pregnancies covered by the Quebec Public Prescription Drug Insurance Program. Opioid exposure was defined as filled at least one prescription for any opioid during pregnancy or before pregnancy but with a duration that overlapped the beginning of pregnancy. Prevalence of opioids use was calculated for all pregnancies, according to pregnancy outcome, trimester of exposure, and individual opioids. The duration of opioid use during pregnancy was analyzed according to 8 categories based on cumulative duration (< 90 days vs. ≥90 days), duration of action (short-acting vs. long-acting) and strength of the opioid (weak vs. strong). Results Of 442,079 eligible pregnancies, 20,921 (4.7%) were exposed to opioids. Among pregnancies ending with deliveries (n = 249,234), 5.4% were exposed to opioids; the prevalence increased by 40.3% from 3.9% in 1998 to 5.5% in 2015, more specifically a significant increase in the second and third trimesters of pregnancy. Weak opioid, codeine was the most commonly dispensed opioid (70% of all dispensed opioids), followed by strong opioid, hydromorphone (11%), morphine (10%), and oxycodone (5%). The prevalence of codeine use decreased by 47% from 4.3% in 2005 to 2.3% in 2015, accompanied by an increased use of strong opioid, morphine (0.029 to 1.41%), hydromorphone (0.115 to 1.08%) and oxycodone (0.022 to 0.44%), from 1998 to 2015. The average durations of opioid exposure were significantly longer among pregnancies exposed to strong opioid as compared to weak opioid regardless of the cumulative duration or duration of action (P < 0.05). Conclusions Given the differences in the safety profile between strong opioids and the major weak opioid codeine, the increased use of strong opioids during pregnancy with longer treatment duration raises public health concerns.

Patterns, trends and determinants of medical opioid utilization in Canada 2005–2020: characterizing an era of intensive rise and fall

Background Into the 21st century, the conflation of high rates of chronic pain, systemic gaps in treatment availability and access, and the arrival of potent new opioid medications (e.g., slow-release oxycodone) facilitated strong increases in medical opioid dispensing in Canada. These persisted until post-2010 alongside rising opioid-related adverse (e.g., morbidity/mortality) outcomes. We examine patterns, trends and determinants of opioid dispensing in Canada, and specifically its 10 provinces, for the years 2005–2020. Methods Raw data on prescription opioid dispensing were obtained from a large national community-based pharmacy database (IQVIA/Compuscript), converted into Defined-Daily-Doses/1,000 population/day for ‘strong’ and ‘weak’ opioid categories per standard methods. Dispensing by opioid category and formulations by province/year was assessed descriptively; regression analysis was applied to examine possible segmentation of over-time strong opioid dispensing. Results All provinces reported starkly increasing strong opioid dispensing peaking 2011–2016, and subsequent marked declines. About half reported lower strong opioid dispensing in 2020 compared to 2005, with continuous inter-provincial differences of > 100 %; weak opioids also declined post-2011/12. Segmented regression suggests breakpoints for strong opioids in 2011/12 and 2015/16, coinciding with main interventions (e.g., selective opioid delisting, new prescribing guidelines) towards more restrictive opioid utilization control. Conclusions We characterized an era of marked rise and fall, while featuring stark inter-provincial heterogeneity in opioid dispensing in Canada. While little evidence for improvements in pain care outcomes exists, the starkly inverting opioid utilization have been associated with extensive population-level harms (e.g., misuse, morbidity, mortality) over-time. This national case study raises fundamental questions for opioid-related health policy and practice.

Quantifying prescribed high dose opioids in the community and risk of overdose

Background Opioid prescribing for a range of health issues is increasing globally. The risk of fatal and non-fatal overdose is increased among people prescribed strong opioids: in high doses in the context of polypharmacy (the use of multiple medications at the same time), especially with other sedatives; and among people with multiple morbidities including cardiorespiratory, hepatic and renal conditions. This study described and quantified the prescribing of strong opioids, comorbidities and other overdose risk factors among those prescribed strong opioids, and factors associated with high/very high opioid dosage in a regional health authority in Scotland as part of a wider service improvement exercise. Methods Participating practices ran searches to identify patients prescribed strong opioids and their characteristics, polypharmacy, and other overdose risk factors. Data were anonymised before being analysed at practice and patient-level. Morphine Equivalent Doses were calculated for patients based on drug/dose information and classed as Low/Medium/High/Very High. Descriptive statistics were generated on the strong opioid patient population and overdose risk factors. The relationship between the prescribing of strong opioids and practice/patient-level factors was investigated using linear and logistic regression models. Results Eighty-five percent (46/54) of GP practices participated. 12.4% (42,382/341,240) of individuals in participating practices were prescribed opioids and, of these, one third (14,079/42,382) were prescribed strong opioids. The most common comorbidities and overdose risk factors among strong opioid recipients were pain (67.2%), cardiovascular disease (43.2%), and mental health problems (39.3%). There was a positive significant relationship between level of social deprivation among practice caseload and level of strong opioid prescribing (p < 0.001). People prescribed strong opioids tended to be older (mean 59.7 years) and female (8638, 61.4%) and, among a subset of patients, age, gender and opioid drug class were significantly associated with prescribing of High/Very High doses. Conclusions Our findings have identified a large population at potential risk of prescription opioid overdose. There is a need to explore pragmatic models of tailored interventions which may reduce the risk of overdose within this group and clinical practice may need to be tightened to minimise overdose risk for individuals prescribed high dose opioids.

POTENTIAL INAPPROPRIATE USE OF STRONG OPIOID ANALGESICS IN CANCER OUTPATIENTS DURING THE LAST YEAR OF LIFE IN FRANCE AND ASSOCIATED FACTORS

Aim: A better knowledge of opioid prescribing patterns would help to identify areas of potential improvement in cancer pain management. This study aimed to identify potential inappropriate use (PIU) of strong opioid analgesics in cancer outpatients in their last year of life. Methods: A retrospective cohort of cancer patients dead between 2011 and 2014 and who were exposed as outpatient to a strong opioid analgesic in the last year of life was identified in the “Echantillon Généraliste de Bénéficiaires” (a 1/97th random sample of the French general population). Prescribing patterns of strong opioids were analyzed and PIU was defined by at least one of these criteria: overlapping prescriptions; contraindicated prescriptions; lack of laxatives; potential drug interactions; prescription in patients hospitalized for opioid-related disorders. Factors associated with PIU were investigated through a multiple logistic regression model. Results: One third of the 2,236 patients (median age 72 years (IQR: 61-82), 44.1% of women) presented a PIU (insufficient laxative prescription (19.6% of patients), insufficient background treatment with transmucosal fentanyl (14.8%), overlapping prescriptions (2.6%)). The rate of PIU significantly decreased from 37.6% (2011) to 29.8% (2014). For patients with a duration of opioid use  3 months, factors associated with PIU were fentanyl prescription (aOR=2.36; 95% CI [1.86-3.00]) and previous use of strong opioid (aOR=1.88; [1.50-2.36]) Conclusion: In France, one third of cancer patients exposed to strong opioids experienced PIU and this proportion tended to decrease over time. There is still room for progress in cancer pain management at the end of life.

First-Line Methadone For Cancer Pain. Titration Time Analysis

Background. Methadone is a low-cost, strong opioid that is increasingly used as a first-line treatment for pain in palliative care (PC). Its long and unpredictable half-life and slow elimination phase can make titration challenging. Evidence for titration modalities is scarce.Objective. To describe the titration phase of the treatment with low dose first-line methadone and the use of methadone for breakthrough pain.Methods. Prospective study with strong opioid-naïve patients with moderate to severe cancer pain followed at a tertiary PC unit in Argentina. Starting methadone dose was 2.5-5 mg/day every 8, 12, or 24 hours. Titration allowed daily dose increases from Day 1, and prescription of oral methadone 2.5 mg every 2 hours with a maximum of 3 rescue doses/day for breakthrough pain. Pain control, methadone stabilization dose, and adverse effects, among other variables, were daily assessed over the first 7 days (T0 –T7).Results. 62 patients were included. Initial median (IQR) methadone dose was 5(2.5) mg/day. Pain intensity decreased from a median (IQR) of 8(2.3) at T0 to 4(2.3) at T1 and remained ≤4 until T7 (all p<0.0001 compared to T0). Similar results were obtained through the categorical and tolerability scales for pain. Fifty patients (81%) reached pain control, 66% in the first 48 hours. Methadone daily dose at T2 and T7 were higher than that at T0: 7.5(3) and 6.7(5.5) versus 5(2.5); respectively (all p<0.05). The opioid escalation index at T7 was 1.7%. The median (IQR) number of rescues, stabilization dose and time for stabilization were 0 (1), 5(4.5) mg and 3(2) days, respectively. Two patients were discontinued due to delirium. All the other side effects were mild.Conclusions. First-line, low-dose methadone using rescue methadone resulted in a pronounced and rapid decrease in pain, with minimal need for titration and for breakthrough doses, and no evidence of accumulation or sedation by the end of the week.