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      Risk of Hip Fracture in Older People Using Selective Serotonin Reuptake Inhibitors and Other Psychoactive Medicines Concurrently: A Matched Case–Control Study in Australia

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          Abstract

          Background

          Few studies have assessed the risk of hip fracture following concurrent use of psychoactive medicines, and none has investigated combinations with selective serotonin reuptake inhibitors.

          Objectives

          To assess the risk of hip fracture in older people as a result of concurrent use of selective serotonin reuptake inhibitors and other psychoactive medicines.

          Methods

          A matched case–control design was employed. Cases were Australian Government Department of Veterans’ Affairs beneficiaries aged over 65 years who experienced a hip fracture between 2009 and 2012. Each case was matched with up to four randomly selected controls of the same age (±2 years) and sex. Medicine-hip fracture associations were estimated via conditional logistic regression. The relative excess risk due to interaction (RERI) was calculated to determine whether combined effects differed from the sum of individual effects.

          Results

          There were 8828 cases and 35,310 controls. The median age of subjects was 88 years and 63% were women. The risk of hip fracture was elevated for all medicines assessed individually, most notably selective serotonin reuptake inhibitors (initiation: odds ratio [OR] = 2.7, 95% confidence interval [CI] 2.1, 3.6) and opioids (initiation: OR = 2.3, 95% CI 1.9, 2.9). Combinations associated with an increased odds of hip fracture included addition of benzodiazepines to selective serotonin reuptake inhibitor therapy (OR = 3.0, 95% CI 1.9, 4.8; RERI = 0.9, 95% CI −0.5, 2.3), concurrent use of both opioids and selective serotonin reuptake inhibitors (OR = 2.2, 95% CI 1.9, 2.6; RERI = 0.1, 95% CI −0.3, 0.5), addition of opioids to selective serotonin reuptake inhibitor therapy (OR = 3.2, 95% CI 1.8, 5.5; RERI = −0.1, 95% CI −2.0, 1.7), and initiation of both benzodiazepines and selective serotonin reuptake inhibitors (OR = 4.7, 95% CI 1.7, 13; RERI = 1.3, 95% CI −3.8, 6.3). The RERI results suggested that the effect of each of these medicine combinations equalled the sum of the effects of individual medicine use.

          Conclusions

          In older people, the concurrent use of selective serotonin reuptake inhibitors and other psychoactive medicines increased the risk of hip fracture as much as the sum of the risks owing to individual medicine use. Our results highlight the need for prescribers to consider the sedative burden of medicines in each older patient as well as the potential for an additive risk of hip fracture when initiating additional psychoactive therapy.

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          Most cited references31

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          Polypharmacy correlates with increased risk for hip fracture in the elderly: a population-based study.

          Few studies have addressed the association between polypharmacy and hip fracture using population data. We conducted a population-based case-control study to investigate whether polypharmacy increases the risk for hip fracture in the elderly. We used insurance claims data from the Taiwan Bureau of National Health Insurance, a universal insurance program with a coverage rate of more than 98% of the population in Taiwan. We identified 2328 elderly patients with newly diagnosed hip fracture during the period 2005-2007. We randomly selected 9312 individuals without hip fracture to serve as the control group. Patient characteristics, drugs prescribed by physicians, and all types of hip fracture were ascertained. The odds ratio (OR) of hip fracture in association with the number of medications used per day in previous years was assessed.We found that patients were older than controls, predominantly female, and more likely to use 5 or more drugs (22.2% vs. 9.3%, p or = 85 years who used 10 or more drugs than for those aged 65-74 years who used 0-1 drug after controlling for covariates (OR, 23.0; 95% CI, 3.77-140).We conclude that the risk of hip fracture in older people increases with the number of medications used, especially in women. Age interacts with the daily medications for the risk of hip fracture.
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            What do case-control studies estimate? Survey of methods and assumptions in published case-control research.

            To evaluate strategies used to select cases and controls and how reported odds ratios are interpreted, the authors examined 150 case-control studies published in leading general medicine, epidemiology, and clinical specialist journals from 2001 to 2007. Most of the studies (125/150; 83%) were based on incident cases; among these, the source population was mostly dynamic (102/125; 82%). A minority (23/125; 18%) sampled from a fixed cohort. Among studies with incident cases, 105 (84%) could interpret the odds ratio as a rate ratio. Fifty-seven (46% of 125) required the source population to be stable for such interpretation, while the remaining 48 (38% of 125) did not need any assumptions because of matching on time or concurrent sampling. Another 17 (14% of 125) studies with incident cases could interpret the odds ratio as a risk ratio, with 16 of them requiring the rare disease assumption for this interpretation. The rare disease assumption was discussed in 4 studies but was not relevant to any of them. No investigators mentioned the need for a stable population. The authors conclude that in current case-control research, a stable exposure distribution is much more frequently needed to interpret odds ratios than the rare disease assumption. At present, investigators conducting case-control studies rarely discuss what their odds ratios estimate.
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              Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic fractures.

              Serotonin transporters have recently been described in bone, raising the possibility that medications that block serotonin reuptake could affect bone metabolism. We assessed current use of selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) and obtained serial bone mineral density (BMD) measurements in a cohort of 2722 older women (mean age, 78.5 years) participating in the Study of Osteoporotic Fractures, a prospective cohort study of community-dwelling women. Hip BMD was measured at the sixth examination and an average of 4.9 years later at the eighth examination. We categorized women as nonusers (used no SSRIs or TCAs at either examination; n=2406), SSRI users (used SSRIs but no TCAs at either examination; n=198), or TCA users (used TCAs but no SSRIs at either examination; n=118). Depressive symptoms were identified using a cutoff score of at least 6 on the Geriatric Depression Scale. After adjustment for potential confounders, including the Geriatric Depression Scale score, mean total hip BMD decreased 0.47% per year in nonusers compared with 0.82% in SSRI users (P<.001) and 0.47% in TCA users (P=.99). Higher rates of bone loss were also observed at the 2 hip subregions for SSRI users. Results were not substantially altered when women who scored at least 6 on the Geriatric Depression Scale were excluded from the analysis. Use of SSRIs but not TCAs is associated with an increased rate of bone loss at the hip in this cohort of older women.
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                Author and article information

                Contributors
                +61 3 5454 8374 , michael.leach@mymail.unisa.edu.au
                Journal
                Drugs Real World Outcomes
                Drugs Real World Outcomes
                Drugs - Real World Outcomes
                Springer International Publishing (Cham )
                2199-1154
                2198-9788
                17 May 2017
                17 May 2017
                June 2017
                : 4
                : 2
                : 87-96
                Affiliations
                [1 ]ISNI 0000 0000 8994 5086, GRID grid.1026.5, Quality Use of Medicines and Pharmacy Research Centre, Sansom Institute, School of Pharmacy and Medical Sciences, , University of South Australia, ; GPO Box 2471, Adelaide, SA 5001 Australia
                [2 ]ISNI 0000 0001 0392 1268, GRID grid.414425.2, Loddon Mallee Integrated Cancer Service, , Bendigo Health Care Group, ; Bendigo, VIC Australia
                [3 ]ISNI 0000 0004 1936 7857, GRID grid.1002.3, School of Rural Health, , Monash University, ; Bendigo, VIC Australia
                Author information
                http://orcid.org/0000-0003-1468-3474
                Article
                107
                10.1007/s40801-017-0107-8
                5457310
                28516333
                9b292990-4608-46f4-9181-23d948d11b97
                © The Author(s) 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100000938, Department of Veterans' Affairs, Australian Government;
                Categories
                Original Research Article
                Custom metadata
                © The Author(s) 2017

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