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BACKGROUND: Chronic high-dose (CHD) prescription opioid use is a major public health concern. Although CHD opioid use has been associated with psychiatric disorders, the causality could go both ways. Some studies have already linked psychiatric disorders to an increased risk of transitioning to chronic opioid use, and longitudinal data identifying psychiatric disorders as predictors of CHD opioid use could shed further light on this issue. AIMS: To prospectively examine the relationship between the presence of a psychiatric disorder and subsequent development of CHD opioid use in primary care patients newly receiving opioids. METHOD: Data were included from 137 778 primary care patients in The Netherlands. Cox regression modelling was used to examine the association between psychiatric disorders prior to a new opioid prescription and subsequent CHD opioid use (≥90 days; ≥50 mg/day oral morphine equivalents) in the subsequent 2 years. RESULTS: Of all patients receiving a new opioid prescription, 2.0% developed CHD opioid use. A psychiatric disorder before the start of an opioid prescription increased the risk of CHD opioid use (adjusted hazard ratio HR = 1.74; 95% CI 1.62-1.88), specifically psychotic disorders, substance use disorders, neurocognitive disorders and multiple co-occurring psychiatric episodes. Similarly, pharmacotherapy for psychosis, substance use disorders and mood and/or anxiety disorders increased the risk of CHD opioid use. Psychiatric polypharmacy conferred the greatest risk of developing CHD opioid use. CONCLUSIONS: Psychiatric disorders increase the risk of developing CHD opioid use in patients newly receiving prescription opioids. To reduce the public health burden of CHD opioid use, careful monitoring and optimal treatment of psychiatric conditions are advised when opioid therapy is initiated.
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OBJECTIVES: Proton pump inhibitors (PPIs) are among the most prescribed medications worldwide, however, there is growing concern regarding potential negative effects on bone health. The aim was to examine the effect of dose and type of PPI use on subsequent use of osteoporosis medication and fractures in older Australian women. METHODS: Data were included from 4432 participants (born 1921-26) in the 2002 survey of the Australian Longitudinal Study on Women's Health. Medication data were from the national pharmaceutical administrative database (2003-2012, inclusive). Fractures were sourced from linked hospital datasets available for four major States of Australia. Competing risk regression models used PPI exposure as a time-dependent covariate and either time to first osteoporosis medication prescription or fracture as the outcome, with death as a competing risk. RESULTS: Of the 2328 PPI users and 2104 PPI non-users, 827 (36%) and 550 (26%) became users of osteoporosis medication, respectively. PPI use was associated with an increased risk of subsequent use of osteoporosis medication (adjusted sub-hazard ratio [SHR]=1.28; 95% confidence interval [CI]=1.13-1.44) and subsequent fracture (SHR=1.29, CI=1.08-1.55). Analysis with PPI categorized according to defined daily dose (DDD), showed some evidence for a dose-response effect (osteoporosis medication: <400 DDD: SHR=1.23, CI=1.06-1.42 and ≥400 DDD: SHR=1.39, CI=1.17-1.65, compared with non-users; SHRs were in the same range for fractures). Esomeprazole was the most common PPI prescribed (22.9%). Analysis by type of PPI use showed an increased subsequent risk for: (1) use of osteoporosis medication for rabeprazole (SHR=1.51, CI=1.08-2.10) and esomeprazole (SHR=1.48, CI=1.17-1.88); and (2) fractures for rabeprazole (SHR=2.06, CI=1.37-3.10). Users of multiple types of PPI also had increased risks for use of osteoporosis medication and fractures. CONCLUSION: An appropriate benefit/risk assessment should be made when prescribing PPIs, especially for esomeprazole and rabeprazole, as osteoporosis and fracture risks were increased in this cohort of elderly females subsequent to PPI prescription.