Abstract
BackgroundAntidepressants are one of the most commonly prescribed medications in young and middle-aged adults, but there is relatively little information on their safety across a range of adverse outcomes in this age group. This study aimed to assess associations between antidepressant treatment and several adverse outcomes in people aged 20–64 years diagnosed with depression.MethodsWe conducted a cohort study in 238,963 patients aged 20–64 years registered with practices across the UK contributing to the QResearch primary care database. Only patients with a first diagnosis of depression were included. Outcomes were falls, fractures, upper gastrointestinal bleed, road traffic accidents, adverse drug reactions and all-cause mortality recorded during follow-up. Cox proportional hazards models were used to estimate hazard ratios associated with antidepressant exposure adjusting for potential confounding variables.ResultsDuring 5 years of follow-up, 4651 patients had experienced a fall, 4796 had fractures, 1066 had upper gastrointestinal bleeds, 3690 had road traffic accidents, 1058 had experienced adverse drug reactions, and 3181 patients died. Fracture rates were significantly increased for selective serotonin reuptake inhibitors (adjusted hazard ratio 1.30, 95% CI 1.21–1.39) and other antidepressants (1.28, 1.11–1.48) compared with periods when antidepressants were not used. All antidepressant drug classes were associated with significantly increased rates of falls. Rates of adverse drug reactions were significantly higher for tricyclic and related antidepressants (1.54, 1.25–1.88) and other antidepressants (1.61, 1.22–2.12) compared with selective serotonin reuptake inhibitors. Trazodone was associated with a significantly increased risk of upper gastrointestinal bleed. All-cause mortality rates were significantly higher for tricyclic and related antidepressants (1.39, 1.22–1.59) and other antidepressants (1.26, 1.08–1.47) than for selective serotonin reuptake inhibitors over 5 years but not 1 year, and were significantly reduced after 85 or more days of treatment with selective serotonin reuptake inhibitors. Mirtazapine was associated with significantly increased mortality rates over 1 and 5 years of follow-up.ConclusionsSelective serotonin reuptake inhibitors had higher rates of fracture than tricyclic and related antidepressants but lower mortality and adverse drug reaction rates than the other antidepressant drug classes. The association between mirtazapine and increased mortality merits further investigation. These risks should be carefully considered and balanced against potential benefits for individual patients when the decision to prescribe an antidepressant is made.
Highlights
Antidepressants are one of the most commonly prescribed medications in young and middle-aged adults, but there is relatively little information on their safety across a range of adverse outcomes in this age group
Results of analyses for fracture Over 5 years of follow-up, the fracture rate was significantly increased for selective serotonin reuptake inhibitors and other antidepressants (1.28, 95% Confidence interval (CI) 1.11–1.48), but not tricyclic and related antidepressants (0.92, 95% CI 0.80–1.06) when compared with periods of time when antidepressants were not being used (Table 2)
There was a significantly lower fracture rate for tricyclic and related antidepressants when directly compared with selective serotonin reuptake inhibitors with significant differences (P < 0.001) between the antidepressant drug classes overall (Table 3)
Summary
Antidepressants are one of the most commonly prescribed medications in young and middle-aged adults, but there is relatively little information on their safety across a range of adverse outcomes in this age group. Depression is a serious condition, common in adults of all ages worldwide [1, 2] It is frequently treated with antidepressant drugs, with many countries reporting substantial increases in the prescribing rates of these drugs in recent decades [3,4,5]. Reports from the US, Canada and UK have shown that antidepressants are one of the most commonly prescribed types of medication in young and middle-aged adults [6,7,8,9], taken by 7% of adults aged 18–39 years and by 14% of adults aged 40–59 in the US [9]. Guidelines recommend that selective serotonin reuptake inhibitors should generally be considered as the first-line treatment for depression [13]
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