The safety and risks of antidepressant treatment in older people: new large UK cohort study


The aim of this study was to establish the relative safety and balance of risks for antidepressant treatment in older people.

The cohort study included 60,746 patients aged 65 years and over diagnosed with depression. The study was based in 570 general practices in the UK supplying data to the QResearch database.

The study objectives were to:

  • 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)
    • other antidepressants
    • commonly prescribed individual drugs with non-use of antidepressant drugs
  • directly compare the risk of adverse events for SSRIs with TCAs;
  • determine associations with dose and duration of antidepressant medication;
  • describe patterns of antidepressant use in older people with depression; and
  • estimate costs of antidepressant medication and primary care visits.

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
  • hyponatraemia

Here’s what the study found:

  • 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)
  • 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.

The authors concluded:

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.

CAC Coupland, P Dhiman, G Barton, R Morriss, A Arthur, T Sach and J Hippisley-Cox. A study of the safety and harms of antidepressant drugs for older people: a cohort study using a large primary care database (PDF). Health Technology Assessment 2011; Vol. 15: No. 28.

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