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. 2020 Mar 17;68(7):1494–1503. doi: 10.1111/jgs.16404

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© 2020 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals, Inc. on behalf of The American Geriatrics Society.

This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

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Association between antidepressant dose and the risk of fractures overall, by therapeutic class, and by drug. Any antidepressant dose: In each jurisdiction, we first modeled use of any antidepressant, where use was represented by a continuous measure of antidepressant dose, and the estimated hazard ratio (HR) represents the risk associated with a one‐unit increase in the standardized adult dose. During periods of nonuse of antidepressants, dose would be represented as zero. Models were adjusted for age, sex, potential treatment indications (depression, anxiety, other mental health issues, pain), conditions that increase the risk of falls (dementia, Parkinson's disease, epilepsy, hypertension, peripheral vascular disease, obesity), and fractures (cardiac problems, stroke, renal disease, cancer, osteoporosis, history of fracture), and concurrent drugs (as time‐dependent exposures, benzodiazepines, antipsychotics, opioids). By class: In each jurisdiction, we estimated a second model, where antidepressant exposure was measured as a time‐varying covariate by therapeutic class (SSRI [selective serotonin uptake inhibitor], SNRI [serotonin norepinephrine reuptake inhibitor], TCA [tricyclic antidepressant], atypical, multiple classes). Antidepressant use in each class was represented by a continuous measure of antidepressant dose, and the estimated HR represents the risk associated with a one‐unit increase in the standardized adult dose for a given therapeutic class. During periods of nonuse of antidepressants, dose would be represented as zero. Models were adjusted for the same potential confounders listed for the any antidepressant model. By drug: In each jurisdiction, we estimated a third model, where antidepressant exposure was measured as a time‐varying exposure by individual drug. All drugs were included in the model and use was represented as a continuous measure of antidepressant dose, and the estimated HR represents the risk associated with a one‐unit increase in the standardized adult dose for a given drug. During periods of nonuse of antidepressants, dose would be represented as zero. Models were adjusted for the same potential confounders listed for the any antidepressant model. HRs are shown when there were at least 300 or more users of a given drug within the respective jurisdiction. The error bars represent the 95% confidence intervals around the HRs. Mtl, Montreal; UK, United Kingdom.