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Objective: To compare how newly initiated treatment with benzodiazepines, Z-hypnotics or both associates with the reception of disability pension among 40,661 individuals of a working age. Design: Prescription register study. Setting: Norwegian nationwide prescriptions socio-economic and disability status data. Methods: Cox regression analyses. Subjects: New benzodiazepine or Z-hypnotic users. Main outcome measure: Time to receive disability pension given benzodiazepine or Z-hypnotic use or both. Additional analyses focused on the benzodiazepine first redeemed. Results: Among new users 8.65% of Z-hypnotic users, 12.29% of benzodiazepines users and 13.96% of combined Z-hypnotic and benzodiazepine users became disability pensioners. Z-hypnotic users were weaker associated with becoming disability pensioners (HR = 0.78, CI: 0.73–0.84) and combined users were stronger associated (HR = 1.09, CI: 1.01–1.17), than benzodiazepine users. Women had higher risk than men for becoming disability pensioners. Higher age, lower education, previous drug use and psychiatrist as first prescriber were risk factors. Comparing first benzodiazepine redeemed; clonazepam initiators were stronger associated with becoming disability pensioners than diazepam initiators were (HR = 2.22, CI: 1.81–2.71). No differences between other benzodiazepine users were found. Conclusions: Adjusting for known risk factors gave lower risk for Z-hypnotic users compared to benzodiazepine users for receiving disability pension. Combined use increased the risk further. Clonazepam initiators are especially at risk. These findings may be helpful in prescribing situations to identify and guide individuals at risk for becoming disability pensioners.

Objective:To compare how newly initiated treatment with benzodiazepines, Z-hypnotics or both associates with the reception of disability pension among 40,661 individuals of a working age. Design:Prescription register study. Setting:Norwegian nationwide prescriptions socio-economic and disability status data. Methods: Cox regression analyses. Subjects:New benzodiazepine or Z-hypnotic users. Main outcome measure:Time to receive disability pension given benzodiazepine or Z-hypnotic use or both. Additional analyses focused on the benzodiazepine first redeemed. Results:Among new users 8.65% of Z-hypnotic users, 12.29% of benzodiazepines users and 13.96% of combined Z-hypnotic and benzodiazepine users became disability pensioners. Z-hypnotic users were weaker associated with becoming disability pensioners (HR = 0.78, CI: 0.73–0.84) and combined users were stronger associated (HR = 1.09, CI: 1.01–1.17), than benzodiazepine users. Women had higher risk than men for becoming disability pensioners. Higher age, lower education, previous drug use and psychiatrist as first prescriber were risk factors. Comparing first benzodiazepine redeemed; clonazepam initiators were stronger associated with becoming disability pensioners than diazepam initiators were (HR = 2.22, CI: 1.81–2.71). No differences between other benzodiazepine users were found. Conclusions:Adjusting for known risk factors gave lower risk for Z-hypnotic users compared to benzodiazepine users for receiving disability pension. Combined use increased the risk further. Clonazepam initiators are especially at risk. These findings may be helpful in prescribing situations to identify and guide individuals at risk for becoming disability pensioners. [ABSTRACT FROM PUBLISHER]

An ultra high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the determination of zopiclone and zolpidem in whole blood, for use in cases with suspected driving under influence of drugs (DUID) and autopsy cases. Sample preparation was performed with liquid–liquid extraction (LLE) using ethyl acetate/n-heptane (80:20, v/v) and 0.1 mL whole blood. Deuterated analogues were used as internal standards (IS) for both compounds. The compounds were separated using a reversed phase C 18 -column (2.1 mm × 100 mm, 1.7 μm), with a flow rate of 0.5 mL/min, 1 μL injected and gradient elution with 5 mM ammonium formate pH 10.2 and acetonitrile. Quantification was done by MS/MS using multiple reaction monitoring (MRM) in positive mode. The run time of the method was 4.5 min including equilibration time. The calibration curves of extracted whole blood standards were fitted by linear-order calibration curves weighted 1/ x , with R 2 values above 0.999 for both compounds. Intermediate precision and accuracies (bias) were 2.4–12.9% RSD and from −5.9 to 6.8%, respectively. Recoveries of the compounds were ≥70%. The lower limit of quantification (LLOQ) for zopiclone was 0.50 nmol/L (0.19 ng/mL) or 0.05 pg injected on column, and 3.5 nmol/mL (1.10 ng/mL) for zolpidem, or 0.27 pg injected on column. The limit of detection (LOD) was 0.2 nmol/L (0.08 ng/mL) for zopiclone and 0.3 nmol/L (0.09 ng/mL) for zolpidem. Matrix effects (ME) were between 108 and 115% when calculated against IS. A comparison with former confirmation LC-MS method at the Norwegian Institute of Public Health, Division of Forensic Medicine (NIPH) was performed during method validation. Good correlation was seen for both compounds. The method has been running on a routine basis for two years, and has proven to be very robust and reliable with satisfactory long term precision and bias and with results for external quality samples corresponding well to consensus mean or median. Zopiclone and zolpidem concentrations in post mortem and ante mortem cases were reported. The method also meets the requirements of the legislative limits for driving under the influence of non-alcohol drugs introduced in the Norwegian Road Traffic Act Law from 2012. [ABSTRACT FROM AUTHOR]