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.