Potentially inappropriate drug use and hip fractures among older people. Pharmacoepidemiological studies
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Over the last decades there has been a major increase in the use of prescribed drugs, especially among older people. Although beneficial in many situations, the use of medications is also associated with potential harms. Older people are particularly vulnerable to adverse effects of drugs use, due to age- and disease-related changes, multimorbidity and (often) complex drug regimens. Psychotropic drugs are known to increase the risk of falling; hip fractures are feared consequences of falls, due to resulting loss of function, and high morbidity and mortality. This thesis is based on two empirical studies. Study I (paper I) investigates drug use and prescribing quality among acutely hospitalized older people. Study II (papers II and III) investigates associations between psychotropic drug use and hip fractures. Drug use and prescribing quality (study I) Aims: To identify inappropriate prescribing among older people (≥ 70) on acute hospital admission and on discharge from an intermediate-care nursing home unit (INHU) and hospital wards (HWs). Furthermore, to compare changes in inappropriate prescribing within and between these groups during stay. Methods: This was an observational study conducted among community-dwelling older people acutely admitted to hospitals in Bergen. The study population comprised 290 (157 transferred to the INHU, 133 treated in HWs) individuals. Drug use was obtained from medication charts. Results: Potentially inappropriate medicines (PIMs) and drug-drug interactions (DDIs) were prevalent among community-dwelling older people acutely admitted to hospital, and increased during stay in hospital or intermediate care nursing home. Concomitant use of several psychotropic drugs and inappropriate drug combinations including non-steroidal anti-inflammatory drugs (NSAIDs) were the PIMs most frequently identified. Serious DDIs were scarce. No reductions in number of drugs, PIMs or DDIs were identified in either setting. Psychotropic drugs and hip fractures (study II) Aims: To examine associations between exposure to antidepressant, anxiolytic or hypnotic drugs and the risk of hip fracture among older people; to examine associations between exposure to hypnotic drugs and the time of hip fracture; and to estimate the share of hip fractures attributable to exposure to antidepressant, anxiolytic and hypnotic drugs (attributable risk). Methods: A nationwide prospective cohort study based on merged data from three registries (the Norwegian Prescription Database, the Norwegian Hip Fracture Registry and the Central Population Registry) was conducted. The study population included all 906,422 individuals born prior to 1945 and living in Norway on study start, January 1, 2005. The study period ended on December 31, 2010. Results: Being exposed to any antidepressant, anxiolytic or hypnotic drug was associated with an excess risk of hip fracture as compared to non-exposure. Being exposed to selective serotonin reuptake inhibitors (SSRIs) and other drugs with high/intermediate serotonergic properties was associated with the greatest excess risk – which was almost 2-fold. We found no evidence that short-acting benzodiazepines (SABs) were safer than long-acting benzodiazepines with regards to hip fracture. People exposed to z-hypnotics were at greatest excess risk at night. The attributable risk of antidepressants was estimated at about 5% and anxiolytics and hypnotics at about 3%. At the population level this corresponds to more than 3000 fractures during the 6 year study period. Conclusion and implications: Study I revealed that inappropriate prescribing was common, increased regardless of setting, and frequently involved psychotropic drugs. In study II clinically relevant associations between widely used psychotropic drugs and the risk of hip fracture were identified. These findings imply that there is need for improving the drug treatment for older people, and that the recommended psychotropic drugs (SSRIs, SABs and zhypnotics) offer no advantages with regard to hip fractures as compared to the traditional alternatives.
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Paper I: Bakken MS, Ranhoff AH, Engeland A, Ruths S. Inappropriate prescribing for older people admitted to an intermediate-care nursing home unit and hospital wards. Scand J Prim Health Care. 2012;30(3):169-175. The article is available at: http://hdl.handle.net/1956/10480
Paper II: Bakken MS, Engeland A, Engesaeter LB, Ranhoff AH, Hunskaar S, Ruths S. Increased risk of hip fracture among older people using antidepressant drugs: data from the Norwegian Prescription Database and the Norwegian Hip Fracture Registry. Age Ageing. 2013;42(4):514-20. The article is not available in BORA due to publisher restrictions. The published version is available at: http://dx.doi.org/10.1093/ageing/aft009
Paper III: Bakken MS, Engeland A, Engesaeter LB, Ranhoff AH, Hunskaar S, Ruths S. Risk of hip fracture among older people using anxiolytic and hypnotic drugs: a nationwide prospective cohort study. Eur J Clin Pharmacol. 2014;70(7):873-80. The article is available at: http://hdl.handle.net/1956/8868