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Antidepressant use and risk of adverse outcomes in people aged 20-64 years: Cohort study using a primary care database

Antidepressant use and risk of adverse outcomes in people aged 20-64 years: Cohort study using a primary care database
Antidepressant use and risk of adverse outcomes in people aged 20-64 years: Cohort study using a primary care database

Background: 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. This study aimed to assess associations between antidepressant treatment and several adverse outcomes in people aged 20-64 years diagnosed with depression. Methods: We 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. Results: During 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. Conclusions: Selective 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.

Adverse effects, Antidepressants, Depression, Falls, Fracture, Gastrointestinal bleed, Mortality
Coupland, Carol
6efd69d5-8f84-45ac-9777-d4b07feeb2e2
Hill, Trevor
7c347407-2cde-4145-9a38-6e4258af6982
Morriss, Richard
fb48ce6f-f557-4e5d-a309-5eb7f6ee6c2e
Moore, Michael
1be81dad-7120-45f0-bbed-f3b0cc0cfe99
Arthur, Antony
90ae53fb-349a-445a-8527-a3bba857a2d7
Hippisley-Cox, Julia
7be524e3-9066-4179-b58f-cb2e16cd02ec
Coupland, Carol
6efd69d5-8f84-45ac-9777-d4b07feeb2e2
Hill, Trevor
7c347407-2cde-4145-9a38-6e4258af6982
Morriss, Richard
fb48ce6f-f557-4e5d-a309-5eb7f6ee6c2e
Moore, Michael
1be81dad-7120-45f0-bbed-f3b0cc0cfe99
Arthur, Antony
90ae53fb-349a-445a-8527-a3bba857a2d7
Hippisley-Cox, Julia
7be524e3-9066-4179-b58f-cb2e16cd02ec

Coupland, Carol, Hill, Trevor, Morriss, Richard, Moore, Michael, Arthur, Antony and Hippisley-Cox, Julia (2018) Antidepressant use and risk of adverse outcomes in people aged 20-64 years: Cohort study using a primary care database. BMC Medicine, 16 (1), [36]. (doi:10.1186/s12916-018-1022-x).

Record type: Article

Abstract

Background: 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. This study aimed to assess associations between antidepressant treatment and several adverse outcomes in people aged 20-64 years diagnosed with depression. Methods: We 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. Results: During 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. Conclusions: Selective 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.

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Accepted/In Press date: 9 February 2018
e-pub ahead of print date: 8 March 2018
Keywords: Adverse effects, Antidepressants, Depression, Falls, Fracture, Gastrointestinal bleed, Mortality

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Local EPrints ID: 418742
URI: http://eprints.soton.ac.uk/id/eprint/418742
PURE UUID: 4dca6bae-caf1-48c3-9065-e8b10f058770
ORCID for Michael Moore: ORCID iD orcid.org/0000-0002-5127-4509

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Date deposited: 21 Mar 2018 17:30
Last modified: 17 Dec 2019 01:46

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Contributors

Author: Carol Coupland
Author: Trevor Hill
Author: Richard Morriss
Author: Michael Moore ORCID iD
Author: Antony Arthur
Author: Julia Hippisley-Cox

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