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Antidepressants linked with significant risk of stroke and fracture

By Lilian Anekwe

Antidepressant prescribing is associated with a significantly increased risk of stroke, falls and fractures in older people, according to analyses of primary care data by UK researchers.

Two analyses by the same team of researchers from the University of Nottingham of the QResearch database – a network of 602 practices in England – found antidepressants increased the stroke rate by up to half, the rate of falls by more than three quarters and the fracture rate by 87% compared with no antidepressant use.

Figures from the NHS information Centre show antidepressants are the 10th most commonly prescribed class of drugs in primary care, with 39 million prescriptions issued in England in 2009.

Although depression is common in older people, clinical trials for antidepressants often under-represent the elderly population so little is known about the risks of adverse events in older patients and the relative safety of individual drugs in this class.

The first cohort consisted of 54,298 patients aged 65 and over without a previous stroke but with a diagnosis of depression recorded between 1996 and 2007.

The rate of stroke during follow-up was significantly increased for selective serotonin reuptake inhibitors (SSRIs) and the drugs listed in the BNF category of other antidepressants, including venlafaxine and mirtazapine.

The highest hazard ratios among the most commonly prescribed drugs were for venlafaxine, where the stroke rate increased by 51%, and mirtazapine, where the stroke rate was increased by 38%, compared with no antidepressant use.

The second analyses looked at a cohort of 55,757 patients with their first recorded falls and 52,907 with their first recorded fractures.

The highest hazard ratios among the most commonly prescribed drugs were a 76% relative increase in risk for citalopram, a 68% increase for venlafaxine, a 66% increase in escitalopram, a 64% increase for fluoxetine and a 63% increase for sertraline.

The fracture rate was also significantly increased for all classes of antidepressant, with hazard ratios highest for venlafaxine, an 87% increase, citalopram, a 62% increase and sertraline, a 60% increase.

The researchers estimated that for each 10,000 patients 81 additional people treated with the class of other antidepressants and 38 additional people on SSRIs would have a stroke in one year.

For each 10,000 patients treated with SSRIS compared with no treatment, 220 additional people would fall in one year and 98 would have a fracture, compared with 103 and 42 respectively for TCAs and 133 and 209 for other antidepressants.

Professor Julia Hippisley-Cox, a GP and director of the QResearch programme, said: ‘Stroke risk significantly increased for SSRIs and the class of other antidepressants in older people. All classes of antidepressant drug are associated with an increased rate of falls and fractures in older people.

'These risks need to be weighed against the potential benefits of these drugs.'

Antidepressants linked with significant risk of stroke and fracture What are the risks?

STROKE (increase in stroke rate when compared to no antidepressant use)
Other antidepressant drugs (BNF chapter 4.3.4) – 37%
Venlafaxine – 51%
Mirtazapine – 38%


FRACTURES (increase in fracture rate when compared to no antidepressant use)
Tricyclic agents – 26%
Other antidepressant drugs – 64%
Venlafaxine – 87%
Citalopram – 62%
Setraline – 60%


FALLS (increase in falls rate when compared to no antidepressant use)
SSRIs – 66%
Citalopram – 76%
Venlafaxine – 68%
Escitalopram – 66%
Fluoxetine – 64%
Setraline – 63%


Society for Academic Primary Care 2010, oral abstracts 058 and 104

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