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Antidepressants work ‘by tackling anxiety symptoms rather than depression’

Benefits seen in the first few weeks of antidepressants seem to be related to a reduction in anxiety, rather than any impact on depression itself, a large trial based on routine GP care has found.

The trial – thought to be the largest not funded by the pharmaceutical industry – also found that the reduction in anxiety symptoms was just as apparent in those with mild to moderate depression, suggesting more patients may benefit than previously thought.

The randomised controlled trial of 550 patients presenting to their GP with depressive symptoms found no evidence that sertraline led to a clinically meaningful reduction in depressive symptoms at six weeks.

But there was strong evidence that the SSRI led to reduced anxiety symptoms – such as worry and restlessness – as well as better mental health-related quality of life, and self-reported improvements in mental health, the researchers report in The Lancet Psychiatry.

There was some evidence that by 12 weeks, the SSRI could have been having some impact on reducing depressive symptoms, the researchers pointed out, but the effect was weak.

The trial was set up to try and replicate a more accurate picture of the effects of the drug in ‘real-life’ general practice.

Patients from 179 practices across London, Bristol, Liverpool and York, took part in the placebo-controlled trial, which threw up some unexpected results.

Study leader Dr Gemma Lewis said based on previous evidence they had expected to see an earlier and larger effect on depression symptoms.

‘The message is that in this population antidepressants do work but they work in a different way from what we expected.

‘It underpins the importance of anxiety symptoms in depression,’ she said.

‘We think by acting early on anxiety, the antidepressant is helping the patient feel better and this is happening even if the impact on the depressive symptoms is small and happening later.’

Dr Lewis added the study would help provide doctors and patients with information about which symptoms are likely to respond and when.

She said the next step was to do a study with a longer follow up.

Professor Azeem Majeed, head of primary care at Imperial College London, said the study had shown some interesting results but had some limitations including that the population finally selected had come from a group of 30,000 who had been invited to take part but declined or didn’t respond.

‘I would be very cautious about proposing greater use of drugs such as sertraline, particularly given the findings in the recent PHE report on long-term use of antidepressants.

He agreed that a longer study was needed to see if the effects on anxiety symptoms were maintained.

He said: ‘I think there needs to be a much bigger focus on the prevention of mental health problems by addressing the wider determinants of health, and better support for non-pharmacological interventions before we propose expanding the use of antidepressants even further.’

Professor Helen Stokes-Lampard, chair of RCGP, said: ‘It is well-established that it often takes a while for patients to feel the full benefits of modern antidepressants and that they work best when taken for significant periods of time, which is one reason why doctors will often review patients after several weeks of use and then prescribe a fairly long course of the drugs, if they appear to be beneficial.

‘This study gives an interesting insight into how a medication primarily used to treat depression may be improving a patients’ health in other ways in the shorter term, by reducing symptoms of anxiety, which is often associated with depression. 

‘It is always encouraging to see continued research into widely-used medications, and it is important that it is taken into account in the development of clinical guidelines so that GPs and other prescribers can continue to provide the best possible care for patients, based on the most up to date evidence.’


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