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Updated: Jan 21, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Risk assessment of using off-label morphine sulfate in a population-based retrospective cohort of opioid-dependent
Célian Bertin1,2, Jessica Delorme1,2, Marie Riquelme1,2
1CHU Clermont-Ferrand, Inserm 1107, Neuro-Dol, Service de Pharmacologie médicale, Centres Addictovigilance et Pharmacovigilance, Centre Evaluation et Traitement de la Douleur, Université Clermont Auvergne, Clermont-Ferrand, France.
Aims:
Several addictovigilance studies have described the off-label use of morphine sulfate (MS) for nonchronic pain in opioid use disorder (OUD) patients as an alternative to conventional opioid substitution treatments (OSTs). This study primarily sought to compare the incidence of unintentional opioid-related overdose in the year following the prescription initiation in off-label MS users, compared to OST-maintained patients.
Methods:
Sequential cohorts of OUD patients who were regularly dispensed MS, buprenorphine, or methadone, between 1 April 2012 and 31 December 2014, were retrospectively identified using the French nationwide healthcare data system. The incidence of overdoses, deaths, doctor shopping, and complications of a viral, bacterial or thrombotic nature, was compared using the Cox regression method.
Results:
Overall, 1075, 20 834 and 9778 OUD patients without chronic-pain were included in the MS, buprenorphine, and methadone cohorts, respectively. Overdose incidence was 3.8 (P < .01 [95% confidence interval (CI): 2.1-6.8]) and 2.0 (P = .02 [95%CI: 1.1-3.6]) higher in the MS cohort vs buprenorphine and methadone, respectively. Death incidence was 9.1 (P < .01 [95%CI: 3.2-25.9]) and 3.9 (P < .01 [95%CI: 1.4-10.7]) higher in the MS cohort vs buprenorphine and methadone, respectively. The incidences of other associated risks were significantly higher in the MS group vs OSTs, except for hepatitis C viral infection and thrombotic complications.
Conclusion:
This first French comprehensive nationwide study reveals increasing overdose, death, bacterial infection, abuse and diversion risks when off-label MS is initiated as alternative to OST. These results question the relevance of prescribing MS as a safe opioid maintenance treatment, considering its health risk profile.
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