OBJECTIVES: The aim of this study was to establish the relative safety and 
balance of risks for antidepressant treatment in older people. The study 
objectives were to (1) determine relative and absolute risks of predefined 
adverse events in older people with depression, comparing classes of 
antidepressant drugs [tricyclic and related antidepressants (TCAs), selective 
serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs) and 
other antidepressants] and commonly prescribed individual drugs with non-use of 
antidepressant drugs; (2) directly compare the risk of adverse events for SSRIs 
with TCAs; (3) determine associations with dose and duration of antidepressant 
medication; (4) describe patterns of antidepressant use in older people with 
depression; and (5) estimate costs of antidepressant medication and primary care 
visits.
DESIGN: A cohort study of patients aged 65 years and over diagnosed with 
depression.
SETTING: The study was based in 570 general practices in the UK supplying data 
to the QResearch database.
PARTICIPANTS: Patients diagnosed with a new episode of depression between the 
ages of 65 and 100 years, from 1 January 1996 to 31 December 2007. Participants 
were followed up until 31 December 2008.
INTERVENTIONS: The exposure of interest was treatment with antidepressant 
medication. Antidepressant drugs were grouped into the major classes and 
commonly prescribed individual drugs were identified.
MAIN OUTCOME MEASURES: There were 13 predefined outcome measures: all-cause 
mortality, sudden cardiac death, suicide, attempted suicide/self-harm, 
myocardial infarction, stroke/transient ischaemic attack (TIA), falls, 
fractures, upper gastrointestinal bleeding, epilepsy/seizures, road traffic 
accidents, adverse drug reactions and hyponatraemia.
RESULTS: In total, 60,746 patients were included in the study cohort. Of these, 
54,038 (89.0%) received at least one prescription for an antidepressant during 
follow-up. The associations with the adverse outcomes were significantly 
different between the classes of antidepressant drugs for seven outcomes. SSRIs 
were associated with the highest adjusted hazard ratios (HRs) for falls [1.66, 
95% confidence interval (CI) 1.58 to 1.73] and hyponatraemia (1.52, 95% CI 1.33 
to 1.75), and the group of other antidepressants was associated with the highest 
HRs for all-cause mortality (1.66, 95% CI 1.56 to 1.77), attempted 
suicide/self-harm (5.16, 95% CI 3.90 to 6.83), stroke/TIA (1.37, 95% CI 1.22 to 
1.55), fracture (1.63, 95% CI 1.45 to 1.83) and epilepsy/seizures (2.24, 95% CI 
1.60 to 3.15) compared with when antidepressants were not being used. TCAs did 
not have the highest HR for any of the outcomes. There were also significantly 
different associations between the individual drugs for seven outcomes, with 
trazodone, mirtazapine and venlafaxine associated with the highest rates for 
several of these outcomes. The mean incremental cost (for all antidepressant 
prescriptions) ranged between £51.58 (amitriptyline) and £641.18 (venlafaxine) 
over the 5-year post-diagnosis period.
CONCLUSIONS: This study found associations between use of antidepressant drugs 
and a number of adverse events in older people. There was no evidence that SSRIs 
or drugs in the group of other antidepressants were associated with a reduced 
risk of any of the adverse outcomes compared with TCAs; however, they may be 
associated with an increased risk for certain outcomes. Among individual drugs 
trazodone, mirtazapine and venlafaxine were associated with the highest rates 
for some outcomes. Indication bias and residual confounding may explain some of 
the study findings. The risks of prescribing antidepressants need to be weighed 
against the potential benefits of these drugs.
FUNDING: The National Institute for Health Research Health Technology Assessment 
programme.