Increased Risk of Hip Fracture Among Older People Using Antidepressant Drugs

Data From the Norwegian Prescription Database and the Norwegian Hip Fracture Registry

Marit Stordal Bakken; Anders Engeland; Lars B. Engesæter; Anette Hylen Ranhoff; Steinar Hunskaar; Sabine Ruths

Disclosures

Age Ageing. 2013;42(4):514-520. 

In This Article

Methods

This was a nationwide prospective study based on merged data from the Norwegian Prescription Database (NorPD),[14] the Norwegian Hip Fracture Registry[15] and the Central Population Registry.[16]

Data Sources

The NorPD, starting from January 2004, contains information on all prescription drugs purchased at all pharmacies in Norway.[17] The data extracted for this study comprises all prescriptions of antidepressants, Anatomical Therapeutic Chemical (ATC) system code[18] N06A, dispensed from January 2004 until December 2010, by the items' ATC code, drug volume by defined daily dose (DDD)[18] and date of dispensing. The NorPD lacks individual information on medication dispensed to people living in nursing homes, ~40,000 at any time.

The Norwegian Hip Fracture Registry, starting from January 2005, contains national data (i.e. injury, fracture and surgery) on people operated on for hip fracture at all 55 hospitals in Norway performing such surgery.[15] For the purpose of this study, we extracted the date of hip fracture, or the date of surgery in case of missing information, for the period January 2005 until December 2010. Although the registry comprises fractures in nursing home patients, these individuals cannot be identified.

The Central Population Registry contains demographic information on the entire population of Norway. The data extracted for this study comprise birth year, sex and date of death or emigration if applicable.

The variables selected from these three registries were linked, using the unique 11-digit personal identity number assigned to everyone living in Norway after 1960.

Study Population

The study population included everyone born before 1945 and living in Norway on 1 January 2005. They were followed up until the day of any first hip fracture, emigration or death or until the end of the study period on 31 December 2010.

Antidepressant Medication

Antidepressant medication was divided in two different ways, according to; (i) therapeutic subgroups (ATC group): TCAs (N06AA), SSRIs (N06AB) and other antidepressants (N06AG, N06AX); (ii) the drugs' serotonergic effects: high or intermediate serotonergic properties, and those with low or no serotonergic properties.[10,19]

Exposure

Since the NorPD does not include information on whether or when the purchasers consumed the dispensed drugs, we had to make assumptions on drug exposure. Antidepressants are usually prescribed in 30 or 100 day lots, and we assumed people to start using them the day they were purchased. Antidepressants are predominantly used on a regular daily basis. The DDD is the assumed average maintenance dose per day for a drug used for its main indication among adults, as defined by the WHO.[18] Because the actually prescribed dose may diverge from the DDD, we calculated the risk of hip fracture for various assumed total exposure times (3 and 14 days and the number of days corresponding to the number of DDDs prescribed, respectively). The latter was considered the best proxy for the number of person-days exposed.

We defined overall use as any exposure to antidepressants within the study period, including all exposure periods. Recently started treatment was defined as the first 14 days of first-time exposure to antidepressants after a 360-day wash-out period.

Statistical Analysis

We compared the incidence of hip fracture during the person-days exposed and unexposed to antidepressants in the study period by calculating standardised incidence ratios (SIRs).[20] An SIR >1 indicates an increased risk of hip fracture associated with exposure. We adjusted the SIRs for sex, birth year and time period (in 2-month intervals). Results based on overall use of antidepressants in the entire study population are presented throughout the article. We performed subanalysis for recently started drug use.

For the SIRs, 95% CIs were calculated assuming a Poisson distribution of the observed number of hip fractures among exposed people, estimating the mean by the expected number of hip fractures among the exposed people.

To calculate the attributable risk of exposure to antidepressant drugs on hip fracture, we divided the observed minus the expected number of fractures during the number of person-days exposed to antidepressant drugs by the observed number of fractures in the study population.

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