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Antidepressants more effective than placebo for acute depression, study finds

All of the most commonly prescribed antidepressants were more effective at treating the symptoms of acute depression in adults than placebo, according to the findings of a major analysis.

The meta-analysis, published this week in the Lancet, looked at over 500 trials including over 116,000 patients with major depressive disorder. The analysis included both placebo-controlled trials and head to head trials, where antidepressants were compared with other antidepressants.

The researchers found that all 21 of the most common antidepressants that they looked at in the study were more effective than placebo for treating acute depression in the first eight weeks of treatment.

Agomelatine and fluoxetine showed the greatest acceptability, with patients 16% and 12% less likely respectively to stop taking their medication compared to placebo. Clomipramine had the worst acceptability, with patients 30% more likely to stop taking it than placebo.

Head to head studies included in the analysis also showed that some antidepressants were more effective than others, with agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine and vortioxetine proving the most effective.

Agomelatine was the most acceptable drug when compared to other antidepressants, with amitriptyline, duloxetine and venlafaxine among the least tolerable.

The researchers said in the paper: ‘All antidepressants were more efficacious than placebo in adults with major depressive disorder. These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants.’

Dr Andrea Cipriani, lead author and senior clinical researcher at the University of Oxford, said: ‘Our findings are relevant for adults experiencing a first or second episode of depression – the typical population seen in general practice.

‘Antidepressants can be an effective tool to treat major depression, but this does not necessarily mean that antidepressants should always be the first line of treatment.’

RCGP chair Professor Helen Stokes-Lampard said: ‘This research should reassure patients who are taking or are contemplating commencing antidepressants, and the doctors that prescribe them, that they are an effective treatment for depression in the short-term.

‘Although antidepressants are of proven benefit - as this study shows - no doctor wants their patients to become reliant on medication so where possible, GPs will explore alternative treatments, such as talking therapies or CBT, which can be of great benefit for some patients.’

It comes as Public Health England was last month tasked by the Government to include antidepressants in a review into prescription drug addiction.

The Lancet; available online 21st February

Readers' comments (15)

  • No, there is still a massive doubt in my mind about ADs
    This is a meta-analysis. Any such meta-analysis is simply a re-jigging of the numbers. You know what they say about statistics.

    Not one single new patient (or should I hastily correct myself and say 'consumer') has been tested here.

    So, are we saying that there are disordered neurotransmitters in the brains of so-called depressed people? If so, how are these substances assayed and how is there is baseline levels altered by these drugs. And how is the level of anti-depression different from presecribing the 'consumer' a large VAT (Vodka and Tonic, 'pace' Arfur Daley) every evening at 6pm

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  • JJ You are scarey

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  • Sorry JJ. What you are saying is scary. If we cannot trust the experts and the evidence then we may as well go back believing that the earth is flat.
    The work is moving to a lack of trust in and denigration of experts in all walks of life. FAKE NEWS

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  • Might be worth considering the response from the Council for Evidence Based Psychiatry - UK?
    Re - "Finally putting to bed the controversy on antidepressants".

    "This statement is irresponsible and unsubstantiated" -

    Overall, the study's findings are highly limited, and do not support increasing antidepressant usage. Antidepressants are already being prescribed to around 10% of the UK population and current guidelines do not even support their use by at least one third of these patients.

    This study, and the media coverage that has accompanied it, will unfortunately do nothing to help reduce this level of unnecessary prescribing and the consequent harms".

    Also: -
    Professor Peter Gotzsche : Nordic Cochrane Centre- states:

    ----- "We have done such an analysis based on clinical study reports of placebo-controlled trials we have obtained from European drug regulators (submitted for publication)".

    "I will not reveal the details before our results have been published, but our results are very different from those shown in the Lancet paper".

    "The use of clinical study reports is crucial. The manufacturers had excluded patients from their analyses, which we were able to include. This is generally not possible for the systematic review done by Cipriani et al.
    So, these results are also flawed and should not be trusted".

    Cum Scientia Caritas?

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  • As far as I am aware this is the 2nd met-analysis done in this area. The first one by Irving Kirsch - try Wikipedia, said no better than placebo. So now we have 2 bits of research to go on. Take note of the words "acute" Short term" and "major". These words do not apply to 90% + of my depressed workload which consists of chronic low grade depression and dependency on long term medication. Unfortunately the simple message now to the public and doctors is that these medication "work" . It is much more complex than that. They also stated that they excluded patients with "resistant" depression. I assume that means they excluded those patients where medication failed - bizarre!
    There is no evidence that serotonin affects mood - it is a theory. There is no evidence that SSRI actually raise serotonin levels in the brain!

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