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Older people taking new generation antidepressants are at more risk of dying or suffering from a range of serious health conditions including stroke, falls, fractures and epilepsy, a study involving researchers at The University of Nottingham has found.

The research, published on British Medical Journal, discovered that selective serotonin reuptake inhibitors ( SSRIs ) are more strongly associated with an increased risk of several adverse outcomes in people over the age of 65 with depression compared with older tricyclic antidepressants ( TCAs ).

The authors say the risks and benefits of different antidepressants should be carefully considered when prescribing these drugs to elderly patients and have called for further research to investigate the findings.

Researchers have found some evidence that the older tricyclic antidepressants may be associated with lower risks of several adverse outcomes compared with newer antidepressants in older people diagnosed as having depression.

Depression is a common condition in older people and antidepressants, particularly SSRIs, are widely used. However, very little is known about the safety of these drugs in older people.

The team of researchers from the Universities of Nottingham and East Anglia set out to investigate the potential link between antidepressant treatment and the risk of a number of potentially life-threatening outcomes in older people.

They identified 60,746 UK patients aged 65 and over with a newly diagnosed episode of depression between 1996 and 2007 using the QResearch primary care database. Many patients had other conditions, such as heart disease and diabetes mellitus, and were taking several medications.

Patients were tracked until the end of 2008. During this time, 89% ( 54,038 ) received at least one prescription for an antidepressant, and a total of 1,398,359 prescriptions for antidepressants were received. Of these 57% were for SSRIs, 31% for TCAs, 0.2% for monoamine oxidase inhibitors ( MAOIs ) and 13.5% for other antidepressants.

Antidepressant use was then analysed against several adverse outcomes including all-cause mortality, attempted suicide or self harm, heart attack, stroke, falls, fractures, epilepsy or seizures and hyponatraemia. After adjusting for factors that could affect the results, including age, sex, severity of depression, other illnesses and use of other medications, the team found that SSRIs and drugs in the group of other antidepressants were associated with an increased risk of several adverse outcomes compared with tricyclic antidepressants.

Those taking SSRIs were more likely to die, suffer a stroke, fall or fracture, have epilepsy or a seizure and have hyponatraemia compared with tricyclic antidepressants. The group of other antidepressants were associated with an increased risk of mortality, attempted suicide or self-harm, stroke, fracture and epilepsy or seizures.

Patients in the study had a 7% risk of dying over one year while they were not taking antidepressants, while the comparable risks were 8.1% when taking TCAs, 10.6% for SSRIs and 11.4% for the group of other antidepressants. For stroke, one-year risks were 2.3%, 2.6% and 3.0% (compared with 2.2% when not on antidepressants ) and for fracture they were 2.2%, 2.7% and 2.8% compared with 1.8%.

Among individual drugs Trazodone ( Desyrel, Trittico ), Mirtazapine ( Remeron ) and Venlafaxine ( Efexor, Effexor ) carried the highest risk for some adverse outcomes.

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

Source: University of Nottingham, 2011

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