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Antidepressants do work after all, major GP trial shows

By Lilian Anekwe

Antidepressants not only work after all, but their use should be extended to milder forms of depression, a major trial based in UK general practice has concluded.

The Health Technology Assessment, obtained by Pulse, concluded that use of SSRIs for patients with mild to moderate depression was cost-effective.

The researchers called for NICE – which rules out use of antidepressants for mild depression – to consider the results when re-evaluating its guidance later this year.

GPs are currently faced with little option but to prescribe drugs to patients with mild depression who face long waits for psychological therapies. A change to NICE guidance would remove the stigma from doing so, and undermine claims that GPs were over-using SSRIs.

The Threshold for Antidepressants (THREAD) study randomised 186 patients with newly-diagnosed episodes of either mild or moderate depression to either supportive GP care or supportive care plus fluoxetine. Each group was assessed using the Hamilton Depression Rating Scale (HDRS) after 12 and 26 weeks.

Depression scores fell in both groups, but by a further three points in patients who received fluoxetine. The effect was sustained at 26 weeks, which researchers said meant the difference was unlikely to be down to a placebo effect.

The efficacy of antidepressants has been the subject of huge controversy in recent weeks, after a meta-analysis including unpublished data concluded they were generally no better than placebos.

Professor Tony Kendrick, professor of primary medical care at the University of Southampton and a GP in the city, presented the research at the UK Mental Health Research Network meeting in London.

He said: ‘Both groups got better and with support alone from GPs there was a drop in HDRS score. But with SSRIs there was a bigger drop and patients seem to get better more quickly.

‘The difference was about three points. It's debatable whether that's clinically significant, but I think GPs keep prescribing because they see the same differences we saw. This does provide some support for what GPs are doing.'

Professor Kendrick added: ‘There's a high probability that adding an SSRI is cost effective at the £30,000 per quality adjusted life year threshold set by NICE.'

Mr Stephen Pilling, consultant clinical psychologist at UCL and member of the NICE depression GDG, said NICE did not rule out antidepressants for mild depression - but favoured other, most cost-effective measures.

'What's emerged from the study does not seem to me to be in principle out of line with what we recommended in the guidance in 2004. But this study is very important and once it is published we will be considering it when we review our guidance. We will also be looking at the ways of classifying mild, moderate and severe depression and offering clarification on this for GPs.'

Dr David Shiers, GP advisor to the National Institute for Mental Health in England, said the trial supported the experience of many GPs.

'The THREAD trial supports what anecdotally many GPs will tell you about the positive clinical effectiveness of the SSRIs for their patients even with mild to moderate depression. This appears to fly in the face of recent well publicised comments of Kirsch and colleagues casting doubt on the efficacy of SSRIs for mild to moderate depression.'

The THREAD Trial

- 95 patients with mild depression, 91 with moderate depression
- 96 were given an SSRI, 90 supportive care
- Follow-up at 12 and 26 weeks
- HDRS score showed significant difference at 12 and 26 weeks, favouring patients given SSRIs, for patients with mild and moderate depression
- Costs were broadly similar in the two groups

Source: UK Mental Health Research Network Scientific Conference 2008


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