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


Age Ageing. 2013;42(4):514-520. 

In This Article


The study population (Appendix 1 in the Supplementary data available at Age and Ageing online) comprised 906,422 people with a mean age of 72.8 years [standard deviation (SD) 8.9 years] on 1 January 2005 (56% women) and mean follow-up 5.2 (SD 1.7) years. Altogether 218,775 persons died (53% women) and 4,949 emigrated (44% women).

A total of 153,301 (17%) people purchased at least one prescription of an antidepressant drug during the study period; 69% were women. Antidepressants with serotonergic properties and SSRIs were most frequently used (Table 1). More women than men used TCAs (31 versus 26% of antidepressant users) and SSRIs (63 versus 58%), with minor sex differences for other subgroups. The use of antidepressants in various subgroups was similar across different birth cohorts, except for TCAs, which decreased with increasing age, from 33% (among those born in 1935–44) to 21% (born before 1915) (not shown).

During the study period, 39,938 individuals experienced a primary hip fracture. Most fractures among the people exposed to antidepressants occurred among those born in 1915–24 (40%) or in 1925–34 (41%). The mean age at the time of fracture was 83 years, and the mean number of days of exposure prior to fracture was 116. Of all hip fractures, 72% occurred in women. Within all birth year cohorts, the prevalence of hip fracture was higher among exposed women than exposed men (Table 2). However, the excess risk of hip fracture was more pronounced among exposed men (SIR = 1.9; 95% CI: 1.8–2.0) than among exposed women (1.7; 1.6–1.7). Sex differences were most prominent in the youngest cohort born in 1935–44 (men 2.9; 2.6–3.4, women 2.5; 2.3–2.7). Generally, for the people using antidepressants, the excess risk of hip fracture decreased with increasing age (Table 2).

Within all antidepressant subgroups, the SIR increased with increasing numbers of assumed exposed person-days from 3 to 14 days, and remained largely stable when SIR was calculated for DDD (not shown).

The risk of hip fracture was elevated among people exposed to any antidepressant drug (SIR = 1.7, 95% CI: 1.7–1.8). The excess risk of hip fracture was higher among people exposed to SSRIs (1.8, 1.7–1.8) than among those exposed to TCAs (1.4, 1.3–1.5) and other antidepressants (1.6, 1.5–1.7). The risk of hip fracture was higher for drugs with high or intermediate serotonergic properties (1.7, 1.7–1.8) than for drugs with no or low serotonergic properties (1.2, 1.1–1.5).

The sex differences in SIR were greatest for SSRIs and drugs with high or intermediate serotonergic effects (Table 3).


The risk of hip fracture was higher during recently started treatment with any antidepressant drug (SIR, all 2.0, 1.5–2.4; women 1.8, 1.3–2.3; men 2.7, 1.7–4.0) and SSRIs (all 2.7, 2.1–3.4; women 2.5, 1.9–3.3; men 3.3, 2.0–5.2) than during overall use (not shown in table). The total number of hip fractures during recently started antidepressant drug use (<100) was too small for analysis regarding TCAs and antidepressants with low or no serotonergic properties to yield representative results.

Attributable Risk

The percentage of hip fractures attributable to exposure to any antidepressant drug was estimated at 4.7%, with TCAs comprising 0.3%, SSRIs 3.6% and other antidepressants 1.0%. Antidepressants with high or intermediate serotonergic properties comprised 4.6% (Table 3).