Antidepressants in Older Patients may have Adverse Outcomes

Posted by: admin on: September 30, 2011

According to the issue of the Cochrane Database Systematic Review of elderly people with depression, tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) have similar efficacy, but TCAs appear to have a higher discontinuation rate because of adverse effects.


Study Synopsis and Perspective

  • Use of antidepressant medication in those over age 65 is risky, new research suggests.
  • A population-based cohort study in the United Kingdom published online August 2 in the British Medical Journal showed significant associations between the use of antidepressants and adverse outcomes, including falls, stroke, seizures, and all-cause mortality in elderly people with depression.
  • Patients prescribed SSRIs, which were the most commonly prescribed antidepressants, fared worse than those receiving the older tricyclic antidepressants, according to the researchers.
  • Carol Coupland said that the findings are new and unexpected, and need to be confirmed in other studies and added that the benefits of the different classes of antidepressant drugs also need to be considered alongside the adverse effects.
  • If the findings are confirmed, then low-dose TCAs should be considered when assessing antidepressant treatment for older people with depression.

Under-Represented Group

  • Little is known about the adverse effects associated with antidepressants in the elderly, who may be at increased risk because of their higher levels of comorbidity, age-related physiological changes, and Polypharmacy said Dr Coupland.
  • Older people are also under-represented in clinical trials of antidepressants, and most of these trials are short-term, which makes it difficult to derive reliable estimates of the incidence of adverse events in this group.
  • Dr. Coupland and team identified 60,746 patients aged 65 to 100 years with a newly diagnosed episode of depression between 1996 and 2007.
    1. The mean age of the patients was 75 years
    2. 33.3% of patients were men
    3. 66.7% were women
    4. Many patients had other conditions, such as heart disease and diabetes, and were taking several medications.
  • They were followed for a mean of 5 years, and the total number of person-years of follow-up was 305,188.


  • During follow-up, 89% of the cohort (n = 54,038) received at least 1 prescription for an antidepressant drug.
  • SSRIs accounted for 54.7%, TCAs made up 31.6%, and the group of other antidepressants (venlafaxine hydrochloride, and mirtazapine) made up 13.5% of prescriptions.
  • Only 0.2% of prescriptions were for monoamine oxidase inhibitors, and patients who were prescribed these drugs were excluded from the analysis.
  • After adjusting for confounding factors, including age, sex, severity of depression, other illnesses, and use of other medications, the study showed that SSRIs and drugs in the group of other antidepressants were associated with an increased risk for several adverse outcomes compared with TCAs.
  • Among individual drugs, trazodone, mirtazapine and venlafaxine were associated with the highest risks for several outcomes.

TCAs Less Risky

  • The absolute risks over 1 year for all-cause mortality were 7.04% for patients, 8.12% for TCAs, 10.61% for SSRIs, and 11.43% for other antidepressants vs no antidepressant use.
  • The most dangerous times for adverse events were within the first 28 days of starting an antidepressant and within the first 28 days after stopping.
  • Doctors should also advise patients that adverse effects are most common during the first few weeks of treatment, and they should be monitored during this period.
  • Study suggests that TCA’s may be less risky but the findings could also be due to residual confounding due to differences between patients prescribed different antidepressant drugs.
  • However this study may prompt further research leading to clearer guidance on how best to treat depression effectively but safely in older people.

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