Selective Serotonin Reuptake Inhibitors and Other Antidepressants and Risk of Fracture |
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Authors: | Peter Vestergaard Lars Rejnmark Leif Mosekilde |
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Institution: | (1) Department of Endocrinology and Metabolism C, Aarhus Amtssygehus, Aarhus University Hospital, Tage Hansens Gade 2, DK-8000 Aarhus C, Denmark |
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Abstract: | Our aim was to study fracture risk in users of various antidepressants (tricyclic antidepressants, selective serotonin reuptake
inhibitors, and the group of other antidepressants including monoamine oxidase B inhibitors and drugs with effect on the norepinephrine
system) and its relationship with effects on inhibition of the cholinergic and serotonin transporter system. We conducted
a case-control study with 124,655 fracture cases and 373,962 age- and gender-matched controls. The exposure was use of antidepressants
and a number of confounders. Among the tricyclic antidepressants, amitriptyline and clomipramine were associated with a dose-dependent
increase in fracture risk, while imipramine and nortriptyline were not. Amityriptyline was associated with an increased risk
of fractures at low doses, while the other tricyclic antidepressants were not. Among the selective serotonin reuptake inhibitors,
citalopram, fluoxetine, and sertraline were associated with a dose-dependent increase in fracture risk, while the increase
was borderline statistically insignificant for paroxetine. The group of other antidepressants was not associated with fracture
risk. The increase in fracture risk was significantly associated with the pharmacodynamic effect on the serotonin transporter
system but not on other signaling systems. The effect of antidepressants on the risk of fractures may be linked to their effect
on the serotonin transporter system. While selective serotonin receptor uptake inhibitors were associated with an increased
fracture risk, tricyclic antidepressants and the group of other antidepressants were not systematically associated with fracture
risk. |
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Keywords: | Selective serotonin reuptake inhibitor Tricyclic antidepressant Antidepressant Fracture |
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