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Newer antidepressants ‘less safe in the elderly’

Older people prescribed selective serotonin reuptake inhibitors are at an increased risk of severe adverse outcomes compared with those taking tricyclic antidepressants, UK general practice research shows.

A study published today online in the BMJ found older patients with depression who were prescribed SSRIs had a higher risk of several adverse outcomes – including all-cause mortality – compared with patients on tricyclics, monoamine oxidase inhibitors and other classes of antidepressant.

Researchers from the University of East Anglia studied the records of 570 practices in the QResearch primary care database to identify 61,000 UK patients aged 65 and over with a newly diagnosed episode of depression between 1996 and 2007, and recorded their adverse events from diagnosis until the end of 2008.

During the follow-up period 89% of patients received at least one prescription for an antidepressant. Some 55% of prescriptions were for SSRIs, 32% for TCAs, 0.2% for monoamine oxidase inhibitors, and 13.5% for other antidepressants.

Patients who were not taking antidepressants at all had an absolute risk of death from any cause in the next year of 7%. The risks of all-cause mortality in the following year were 8.1% for those taking TCAs, 10.6% for SSRIs, and 11.4 % for the group of other antidepressants.

SSRIs were also associated with the highest adjusted hazard ratios for falls, a 66% increased risk, and a 52% increased risk of hyponatraemia compared with when antidepressants were not being used.

Among individual drugs, trazodone, mirtazapine and venlafaxine were associated with the highest risks for several outcomes, including attempted suicide or self harm, heart attack, stroke, fractures, epilepsy and seizures,.

Rates of most outcomes were highest in the first 28 days after starting an antidepressant, and also in the first 28 days after stopping.

Professor Julia Hippisley-Cox, professor of clinical epidemiology and general practice at the Unviersity of Nottingham and a GP in the city, concluded: ‘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.'

‘To our knowledge, this is the first published systematic assessment of the safety of commonly used antidepressants in older patients across a range of serious adverse outcomes.'

‘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.'

BMJ 2011, online 3 August