A pharmacoepidemiological cohort study of subjects starting strong opioids for nonmalignant pain: A study from the Norwegian Prescription Database

Clinical studies of short duration have demonstrated that strong opioids improve pain control in selected patients with chronic nonmalignant pain. However, high discontinuation rates and dose escalation during long-term treatment have been indicated. The aim of the present study was to determine discontinuation rates, dose escalation, and patterns of co-medication with benzodiazepines. The Norwegian Prescription Database provides complete national data at an individual level on dispensed drugs. A complete national cohort of new users of strong opioids was followed up for 5 years after initiation of therapy with strong opioids. Of the 17,248 persons who were new users of strong opioids in 2005, 7229 were dispensed a second prescription within 70 days and were assumed to be intended long-term users. A total of 1233 persons in the study cohort were still on opioid therapy 5 years later. This equals 24% of the study cohort who were still alive. Of the participants, 21% decreased their annual opioid dose by 25% or more, whereas 21% kept a stable dose (±24%) and 34% more than doubled their opioid dose from the first to the fifth year. High annual doses of opioids were associated with high annual doses of benzodiazepines at the end of follow-up. It is an issue of major concern that large dose escalation is common during long-term treatment, and that that high doses of opioids are associated with high doses of benzodiazepines. These findings make it necessary to question whether the appropriate patient population receives long-term opioid treatment.