ArticleAddiction (Abingdon, England)2020
Impact of opioid dose escalation on the development of substance use disorders, accidents, self-inflicted injuries, opioid overdoses and alcohol and non-opioid drug-related overdoses: a retrospective cohort study.
Article in Addiction (Abingdon, England), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 51 citations in OpenAlex.
- Predictors of fatal and nonfatal overdose after prescription of opioids for chronic pain: a systematic review and meta-analysis of observational studies.CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne · 2023Pooled it
- Co-Occurring Trauma and Non-Suicidal Self-Injury Among People With Chronic Pain: A Systematic Review.Current pain and headache reports · 2021Pooled it
- Alexithymia mediates white-matter microstructure and substance use escalation in trauma-exposed individuals.Journal of affective disorders · 2026Article
- Long-Term Opioid Therapy Tapering and Risk of Substance Use Disorder and Overdose: Differences by Opioid Dose and Duration.Journal of general internal medicine · 2026Article
- Substance use risk and controlled substances discussions in cancer care: Observations from audio-recorded patient-clinician encounters.Palliative & supportive care · 2026Article
- Behavioral and transcriptomic markers of susceptibility to escalate fentanyl intake.Translational psychiatry · 2026Article
- Buprenorphine Substitution as a Tapering Strategy for Opioid Discontinuation in Patients with Chronic Pain: A Nonrandomized and Proof of Concept Study.Pain and therapy · 2025Article
- Predicting postoperative chronic opioid use with fair machine learning models integrating multi-modal data sources: a demonstration of ethical machine learning in healthcare.Journal of the American Medical Informatics Association : JAMIA · 2025Article
- A pH-sensitive opioid does not exhibit analgesic tolerance in a mouse model of colonic inflammation.British journal of pharmacology · 2025Article
- Opioid therapy trajectories of patients with chronic non-cancer pain over 1 year of follow-up after initiation of short-acting opioid formulations.Pain medicine (Malden, Mass.) · 2024Article
- Glycine Transporter 1 Inhibitors: Predictions on Their Possible Mechanisms in the Development of Opioid Analgesic Tolerance.Biomedicines · 2024Review
- Mapping functional traces of opioid memories in the rat brain.Brain communications · 2024Article
- Long-term Safety, Dose Stability, and Efficacy of Opioids for Patients With Restless Legs Syndrome in the National RLS Opioid Registry.Neurology · 2023Article
- Risk Factors for Emergency Department Presentations after the Initiation of Opioid Analgesics in Non-Cancer Patients in Korea: A Nationwide Study.Medicina (Kaunas, Lithuania) · 2023Article
- Patching holes in the mechanism of opioid tolerance.Trends in pharmacological sciences · 2023Article
- Prenatal heroin exposure alters brain morphology and connectivity in adolescent mice.NMR in biomedicine · 2023Article
- The NOpioid Project: a prospective observational feasibility study examining the implementation of a non-narcotic post-operative pain control regimen.Surgical endoscopy · 2022Observational
- Intraoperative Interpectoral and Subserratus Nerve Blocks in Breast Augmentation Surgery.Plastic and reconstructive surgery. Global open · 2022Article
- Association between opioid therapy trajectories and potential opioid-related adverse health events.Pharmacoepidemiology and drug safety · 2022Article
- Initiation of Opioid Prescription and Risk of Suicidal Behavior Among Youth and Young Adults.Pediatrics · 2022Article
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
aimTo understand the potential harmful effects of dose escalation among patients with chronic, non-cancer pain (CNCP) on chronic opioid therapy.
designRetrospective cohort study.
settingUnited States Veterans Healthcare Administration.
participantsVeterans with CNCP and on chronic opioid therapy were identified using data from fiscal years 2008-15. The Veteran sample was approximately 90% male and 70% white. MEASUREMENTS: Dose escalators [increase of > 20% average morphine milligram equivalent (MME) daily dose] were compared with dose maintainers (change of ±20% average MME daily dose). A composite measure of subsequent substance use disorders (SUDs: opioid, non-opioid and alcohol use disorders) and opioid-related adverse outcomes (AOs: accidents resulting in wounds/injuries, opioid-related and alcohol and non-opioid medication-related accidents and overdoses, self-inflicted injuries) as well as the individual SUDs and AOs was examined. The primary analyses were conducted among a 1 : 1 matched sample of escalators and maintainers matched on propensity score and index date. Propensity scores were generated using demographic characteristics, medical comorbidities, medication and health-care utilization characteristics. Subgroup analyses were conducted by quartile of the propensity score. Sensitivity analyses were conducted using adjusted logistic regression, logistic regression using stabilized inverse probability of treatment weighting (SIPTW) and instrumental variable (IV) models using geographic variation in opioid dose escalation as the IV.
findingsThere were 32 420 maintainers and 20 767 escalators resulting in 19 358 (93.2%) matched pairs. Composite AOs [odds ratio (OR) = 1.31, 95% confidence interval (CI) = 1.23, 1.40], composite SUDs (OR = 1.31, 95% CI = 1.22, 1.41) and individual SUD and AO subtypes were higher among dose escalators, except for opioid-related accidents and overdoses and violence-related injuries. Subgroup analyses within the propensity score quartiles found similar results. Sensitivity analyses with the adjusted and SIPTW logistic regressions found similar results to the primary analyses for all outcomes except for opioid-related accidents and overdoses, which were found to be significantly higher among escalators. Sensitivity analyses with IV models provided mixed results with SUDs and the individual types of AOs.
conclusionEscalating the opioid dose for those with chronic, non-cancer pain is associated with increased risks of substance use disorder and opioid-related adverse outcomes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.