Real-world patterns of opioid therapy initiation in Spain, 2012–2018: A population-based, retrospective cohort study with 957,080 patients and 1,509,488 initiations

Abstract

Introduction: Europe has seen a steady increase in the use of prescription opioids, especially in non-cancer indications. Epidemiological data on the patterns of use of opioids is required to optimize prescription. We aim to describe the patterns of opioid therapy initiation for non-cancer pain and characteristics of patients treated in a region with five million inhabitants in the period 2012 to 2018.Methods: Population-based retrospective cohort study of all adult patients initiating opioid therapy for non-cancer pain in the region of Valencia. We described patient characteristics at baseline and the characteristics of baseline and subsequent treatment initiation. We used multinominal regression models to identify individual factors associated with initiation.Results: A total of 957,080 patients initiated 1,509,488 opioid treatments (957,080 baseline initiations, 552,408 subsequent initiations). For baseline initiations, 738,749 were with tramadol (77.19%), 157,098 with codeine (16.41%) 58,436 (6.11%) with long-acting opioids, 1,518 (0.16%) with short-acting opioids and 1,279 (0.13%) with ultrafast drugs. When compared to tramadol, patients initiating with short-acting, long-acting and ultrafast opioids were more likely to be older and had more comorbidities, whereas initiators with codeine were more prone to be healthier and younger. Treatments lasting less than 7 days accounted for 41.82% of initiations, and 11.89% lasted more than 30 days. 19.55% of initiators with ultrafast fentanyl received more than 120 daily Morphine Milligram Equivalents (MME), and 16.12% of patients initiating with long-acting opioids were prescribed more than 90 daily MME (p < 0.001). Musculoskeletal indications accounted for 65.05% of opioid use. Overlap with benzodiazepines was observed in 24.73% of initiations, overlap with gabapentinoids was present in 11.04% of initiations with long-acting opioids and 28.39% of initiators with short-acting opioids used antipsychotics concomitantly. In subsequent initiations, 55.48% of treatments included three or more prescriptions (vs. 17.60% in baseline initiations) and risk of overlap was also increased.Conclusion: Opioids are initiated for a vast array of non-oncological indications, and, despite clinical guidelines, short-acting opioids are used marginally, and a significant number of patients is exposed to potentially high-risk patterns of initiation, such as treatments lasting more than 14 days, treatments surpassing 50 daily MMEs, initiating with long-acting opioids, or hazardous overlapping with other therapies.

Initial opioid prescription characteristics and risk of opioid misuse, poisoning and dependence: retrospective cohort study

“… 27 Also, we previously showed in this same population that, when compared with tramadol, patients initiating with short-acting, long-acting and ultrafast opioids were more likely to be older and have more comorbidities. 27 In this sense, and despite we adjusted for observed confounders, unmeasured differences in individual characteristics may still be affecting our risk estimates.…”

“…The patterns of use of opioid medications for mild respiratory-related conditions, such as colds and influenza (96% of which are fixed-dose combinations of codeine or tramadol with paracetamol or ibuprofen, commercial presentations that mimic and appear to be used as substitutes to traditional paracetamol combinations with other drugs such as antihistamine or decongestive agents, that in turn are massively used in our setting to treat mild respiratory symptoms), could constitute potential inappropriate care and warrant further investigation 27. Also, we previously showed in this same population that, when compared with tramadol, patients initiating with short-acting, long-acting and ultrafast opioids were more likely to be older and have more comorbidities 27. In this sense, and despite we adjusted for observed confounders, unmeasured differences in individual characteristics may still be affecting our risk estimates.…”

“…In Spain, the yearly volume of prescription opioids and number of patients with at least one prescription doubled, whereas the intensity of treatments in terms of morphine milligram equivalents (MME) tripled from 2010 to 2018 26. Also, opioids were initiated for a vast array of non-oncological indications, and a significant number of patients were exposed to potentially high-risk patterns of initiation, such as treatments lasting >14 days, treatments surpassing 50 daily MMEs, initiating therapy with long-acting opioids or hazardous overlapping with other therapies 27. Whether these patterns of prescription are associated with an increased risk of MPD remains unknown.…”

“… 26 Also, opioids were initiated for a vast array of non-oncological indications, and a significant number of patients were exposed to potentially high-risk patterns of initiation, such as treatments lasting >14 days, treatments surpassing 50 daily MMEs, initiating therapy with long-acting opioids or hazardous overlapping with other therapies. 27 Whether these patterns of prescription are associated with an increased risk of MPD remains unknown.…”

Phase III study of bilayer sustained-release tramadol tablets in patients with cancer pain: a double-blind parallel-group, non-inferiority study with immediate-release tramadol capsules as an active comparator

“…Overall, these findings indicate that twice-daily administration of the bilayer tablets is as effective as fourtimes-daily IR tramadol for managing cancer pain. Opioids are frequently used to manage cancer pain [15][16][17][18][19][20][21], due to their effectiveness and inclusion in clinical guidelines/recommendations [4][5][6][7][8]. Furthermore, studies have shown that opioids can improve QOL by alleviating cancer-related pain [22][23][24][25][26][27].…”