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Antidepressant use and risk of adverse outcomes in older people: population based cohort study

BMJ 2011; 343 doi: (Published 02 August 2011) Cite this as: BMJ 2011;343:d4551
  1. Carol Coupland, associate professor in medical statistics1,
  2. Paula Dhiman, research statistician1,
  3. Richard Morriss, professor of psychiatry and community mental health2,
  4. Antony Arthur, associate professor in elder care3,
  5. Garry Barton, senior lecturer in health economics4,
  6. Julia Hippisley-Cox, professor of clinical epidemiology and general practice1
  1. 1Division of Primary Care, University of Nottingham, Nottingham NG7 2RD, UK
  2. 2Division of Psychiatry, University of Nottingham
  3. 3Division of Nursing, University of Nottingham
  4. 4Health Economics Group (HEG), School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, UK
  1. Correspondence to: C Coupland carol.coupland{at}
  • Accepted 13 June 2011


Objectives To investigate the association between antidepressant treatment and risk of several potential adverse outcomes in older people with depression and to examine risks by class of antidepressant, duration of use, and dose.

Design Cohort study of people aged 65 and over diagnosed as having depression.

Setting 570 general practices in the United Kingdom supplying data to the QResearch primary care database.

Participants 60 746 patients diagnosed as having a new episode of depression between the ages of 65 and 100 years from 1 January 1996 to 31 December 2007 and followed up until 31 December 2008.

Main outcome measures Hazard ratios associated with antidepressant use for all cause mortality, attempted suicide/self harm, myocardial infarction, stroke/transient ischaemic attack, falls, fractures, upper gastrointestinal bleeding, epilepsy/seizures, road traffic accidents, adverse drug reactions, and hyponatraemia, adjusted for a range of potential confounding variables. Hazard ratios were calculated for antidepressant class (tricyclic and related antidepressants, selective serotonin reuptake inhibitors, other antidepressants), dose, and duration of use and for commonly prescribed individual drugs.

Results 54 038 (89.0%) patients received at least one prescription for an antidepressant during follow-up. A total of 1 398 359 antidepressant prescriptions were issued: 764 659 (54.7%) for selective serotonin reuptake inhibitors, 442 192 (31.6%) for tricyclic antidepressants, 2203 (0.2%) for monoamine oxidase inhibitors, and 189 305 (13.5%) for the group of other antidepressants. The associations with the adverse outcomes differed significantly between the antidepressant classes for seven outcomes. Selective serotonin reuptake inhibitors were associated with the highest adjusted hazard ratios for falls (1.66, 95% confidence interval 1.58 to 1.73) and hyponatraemia (1.52, 1.33 to 1.75) compared with when antidepressants were not being used. The group of other antidepressants was associated with the highest adjusted hazard ratios for all cause mortality (1.66, 1.56 to 1.77), attempted suicide/self harm (5.16, 3.90 to 6.83), stroke/transient ischaemic attack (1.37, 1.22 to 1.55), fracture (1.64, 1.46 to 1.84), and epilepsy/seizures (2.24, 1.60 to 3.15), compared with when antidepressants were not being used. Tricyclic antidepressants did not have the highest hazard ratio for any of the outcomes. Significantly different associations also existed between the individual drugs for the same seven outcomes; trazodone (tricyclic antidepressant), mirtazapine, and venlafaxine (both in the group of other antidepressants) were associated with the highest rates for some of these outcomes. Absolute risks over 1 year for all cause mortality were 7.04% for patients while not taking antidepressants, 8.12% for those taking tricyclic antidepressants, 10.61% for selective serotonin reuptake inhibitors, and 11.43% for other antidepressants.

Conclusions Selective serotonin reuptake inhibitors and drugs in the group of other antidepressants were associated with an increased risk of several adverse outcomes compared with tricyclic antidepressants. Among individual drugs, trazodone, mirtazapine, and venlafaxine were associated with the highest risks for some outcomes. As this is an observational study, it is susceptible to confounding by indication, channelling bias, and residual confounding, so differences in characteristics between patients prescribed different antidepressant drugs that could account for some of the associations between the drugs and the adverse outcomes may remain. Further research is needed to confirm these findings, but the risks and benefits of different antidepressants should be carefully evaluated when these drugs are prescribed to older people.


  • We thank the practices and patients who provide data to QResearch. This project was funded by the NIHR Health Technology Assessment Programme (project number 06/42/01) and will be published in full in Health Technology Assessment. Further information about the project is available on the HTA programme website (

  • Contributors: CC was involved in the conception and design of the study, analysing and interpreting data, and reviewing the literature; she wrote the draft manuscript. PD was involved in the design of the study, statistical analysis, interpreting data, and reviewing the literature. RM and AA were involved in the conception and design of the study, interpretation of data, and reviewing the literature. GB was involved in interpretation of data and reviewing the literature. JH-C was involved in the conception and design of the study, extracted the data, and was involved in interpretation of data and reviewing the literature. All authors critically reviewed the paper. CC is the guarantor.

  • Funding: This project was funded by the NIHR Health Technology Assessment Programme (project number 06/42/01). The views and opinions expressed are those of the authors and do not necessarily reflect those of the Department of Health.

  • Competing interests: All authors have completed the Unified Competing Interest form at (available on request from the corresponding author) and declare: all authors had financial support from the NIHR Health Technology Assessment Programme (project number 06/42/01) for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; JH-C is director of QResearch, which is a not for profit venture between the University of Nottingham and EMIS (commercial supplier of general practice clinical computer systems), and director of ClinRisk Ltd (medical software company); RM has received financial support for speaking at meetings sponsored by several pharmaceutical companies about the non-drug treatment of depression and bipolar disorder; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: The project was independently peer reviewed by the QResearch Scientific Board and has been reported to Trent Research Ethics Committee in accordance with the agreed procedure.

  • Data sharing: The patient level data from the QResearch databases are specifically licensed according to the governance framework. See for further details.

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