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Network meta-analysis led by Dr Andrea Cipriani of 522 trials includes the largest amount of unpublished data to date.

A major study comparing 21 commonly used antidepressants concludes that all are more effective than placebo for the short-term treatment of acute depression in adults, with effectiveness ranging from small to moderate for different drugs.

The international study, published in The Lancet, is a network meta-analysis of 522 double-blind, randomised controlled trials comprising a total of 116477 participants. The study includes the largest amount of unpublished data to date, and all the data from the study have been made freely available online.

Our study brings together the best available evidence to inform and guide doctors and patients in their treatment decisions. We found that the most commonly used antidepressants are more effective than placebo, with some more effective than others. 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. Medication should always be considered alongside other options, such as psychological therapies, where these are available. Patients should be aware of the potential benefits from antidepressants and always speak to the doctors about the most suitable treatment for them individually.
- Dr Andrea Cipriani, University of Oxford Department of Psychiatry

An estimated 350 million have depression worldwide. The economic burden in the USA alone has been estimated to be more than US$210 billion. Pharmacological and non-pharmacological treatments are available but because of inadequate resources, antidepressants are used more frequently than psychological interventions. However, there is considerable debate about their effectiveness.

As part of the study, the authors identified all double-blind, randomised controlled trials (RCTs) comparing antidepressants with placebo, or with another antidepressants (head-to-head trials) for the acute treatment (over 8 weeks) of major depression in adults aged 18 years or more. The authors then contacted pharmaceutical companies, original study authors, and regulatory agencies to supplement incomplete reports of the original papers, or provide data for unpublished studies.

The primary outcomes were efficacy (number of patients who responded to treatment, i.e. who had a reduction in depressive symptoms of 50% or more on a validated rating scale over 8 weeks) and acceptability (proportion of patients who withdrew from the study for any reason by week 8).

Overall, 522 double-blind RCTs done between 1979 and 2016 comparing 21 commonly used antidepressants or placebo were included in the meta-analysis, the largest ever in psychiatry. A total of 87052 participants had been randomly assigned to receive a drug, and 29425 to receive placebo. The majority of patients had moderate-to-severe depression.

All 21 antidepressants were more effective than placebo, and only one drug (clomipramine) less acceptable than placebo.

Some antidepressants were more effective than others, with agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine proving most effective, and fluoxetine, fluvoxamine, reboxetine, and trazodone being the least effective. The majority of the most effective antidepressants are now off patent and available in generic form.

Antidepressants also differed in terms of acceptability, with agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine proving most tolerable, and amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine being the least tolerable.

The authors note that the data included in the meta-analysis covers 8-weeks of treatment, so may not necessarily apply to longer term antidepressant use. The differences in efficacy and acceptability between different antidepressants were smaller when data from placebo-controlled trials were also considered.

In order to ensure that the trials included in the meta-analysis were comparable, the authors excluded studies with patients who also had bipolar depression, symptoms of psychosis or treatment resistant depression, meaning that the findings may not apply to these patients. “Antidepressants are effective drugs, but, unfortunately, we know that about one third of patients with depression will not respond. With effectiveness ranging from small to moderate for available antidepressants, it’s clear there is still a need to improve treatments further,” adds Dr Cipriani.

409 (78%) of 522 trials were funded by pharmaceutical companies, and the authors retrieved unpublished information for 274 (52%) of the trials included in the meta-analysis. Overall, 46 (9%) trials were rated as high risk of bias, 380 (78%) as moderate, and 96 (18%) as low. The design of the network meta-analysis and inclusion of unpublished data is intended to reduce the impact of individual study bias as much as possible. Although this study included a significant amount of unpublished data, a certain amount could still not be retrieved.

Antidepressants are routinely used worldwide yet there remains considerable debate about their effectiveness and tolerability. By bringing together published and unpublished data from over 500 double blind randomised controlled trials, this study represents the best currently available evidence base to guide the choice of pharmacological treatment for adults with acute depression. The large amount of data allowed more conclusive inferences and gave the opportunity also to explore potential biases.- Professor John Ioannidis, from the Departments of Medicine, Health Research and Policy, Biomedical Data Science, and Statistics, Stanford University, USA

The authors note that they did not have access to individual-level data so were only able to analyse group differences. For instance, they could not look at the effectiveness or acceptability of antidepressants in relation to age, sex, severity of symptoms, duration of illness or other individual-level characteristics.

The findings from this study contrast with a similar analysis in children and adolescents, which concluded that fluoxetine was probably the only antidepressant that might reduce depressive symptoms. The authors note that the difference may be because depression in young people is the result of different mechanisms or causes, and note that because of the smaller number of studies in young people there is great uncertainty around the risks and benefits of using any antidepressants for the treatment of depression in children and adolescents. 

Read the study in The Lancet.

Read more about Dr Andrea Cipriani.




 andrea cipriani, bbc world service, feb 22 2018


media round up

Wednesday 21 February 2018

Daily Telegraph online, 11.30pm - The drugs do work: anti-depressants should be given to a million more Britons, largest ever review claims

Reuters, 11.35pm - Study seeks to end antidepressant debate: the drugs do work

Time magazine - These Antidepressants Are Most Effective, Study Says

Channel News Asia (Singapore),

Thursday 22 February 2018

Broadcast – TV and Radio

BBC Five Live - - 6-6.14am - live interview with Andrea Cipriani

BBC Five Live – Your Call – 9-10am - phone-in discussion on paper:

Radio: BBC Radio 4, Today – 6.49-6.54am - live interview with Andrea Cipriani (49.30 – 54.00)

BBC News - Victoria Derbyshire – 10.10-10.22am – studio interview with Andrea Cipriani  (from 1:10:10 to 1:21:49)

BBC News – interview ft Henry Hardy and Dr Sarah Lotzof (11.48)

BBC Two – Newsnight – 10.39-10.49pm – ‘Study Finds Anti-Depressants Work’ – interview with Andrea; case study; studio discussion (From 19:35 to 29:20)

BBC World Service – Newshour – interview with Andrea Cipriani (39.27-46.25)
Clip of interview (embeddable)

CTV News (Canada) -
Interviews with John Geddes; Sagar Parikh (wrote Commentary in The Lancet)


TV: BBC World News, Newsday, 00:15

Radio: BBC World Service, The Newsroom, 02:26

Radio: BBC World Service, Outlook, 04:06

Radio: LBC 97.3, Steve Allen, 05:01

Radio: BBC Radio 4, News Briefing, 05:32

TV: Sky News, Sunrise with Sarah-Jane Mee, 06:11

TV: BBC 1, Breakfast, 06:04

TV: BBC World News Channel, News, 14:42

Print / online

The Guardian, p.1, Sarah Boseley - Depression: the drugs do work, say experts

The Guardian, Mark Rice-Oxley, It's official: antidepressants are not snake oil or a conspiracy – they work

The Sun, p.1 & 9, Nick Mcdermott – Pop More Happy Pills / The drugs do work

The Times, p.1, Chris Smyth - More people should get pills to beat depression

Daily Mail, p.5, Kate Pickles - A million more of us should be taking antidepressants

The Independent Daily Edition, p.18, Shehab Khan - Antidepressants work and should be prescribed more

Metro – Antidepressants are effective in treating mental health, major study finds

Daily Express, Antidepressants DO work and millions more should be on them

Mail Online UK, The drugs do work - study suggests antidepressants are effective

Daily Mirror, p.13, Lucy Clarke-Billings - ‘Put more on pills to tackle depression’

Hindustan Times, Do antidepressants really work? We finally have an answer

Japan Times, The drugs do work: Study seeks to end antidepressant debate

International Business Times UK, Which are the best drugs to treat depression and what are the side effects?

Global Times, Study settles debate on drugs to heal depression

CBC, Antidepressant drugs do work, review on almost 120,000 patients concludes

BBC News – ‘Anti-depressants: Major study finds they work’
Scientists say they have settled one of medicine's biggest debates after a huge study found that anti-depressants work.

BBC News – ‘Anti-depressants: ‘There’s still a stigma’
A comedian who found anti-depressants helped said he thought there was still a stigma around the drugs.

BBC News – Health – ‘Whatever the medication is doing, it’s keeping me going’
As scientists release a study showing that anti-depressants work, some users of the medication share their experiences on how it has affected their lives.

BBC - clip - Antidepressants help with treatment of depression, study finds

Sky News - Antidepressants really do work, study suggests - While all the antidepressants were shown to work in the study, some were shown to be far more effective than others.

Huffington Post UK, Anti-Depressants Are An Effective Treatment For Depression, Major Study Finds

Huffington Post UK, Mental Health Charities Slam The Sun For Calling Anti-Depressants `Happy Pills''

Der Spiegel - Antidepressants - How well do medications work against depression? – ‘Antidepressants more effective than placebo

University of Oxford - Study seeks to end antidepressant debate: the drugs do work

Friday 23 February 2018

New Statesman – Mark Brown – ‘Stop vilifying antidepressants – mental health is more complex than the “insteaders” think’

iNews – Health – ‘Here’s what you actually need to know before taking antidepressants’

The Guardian, Letters, ‘Why we are sceptical of antidepressant analysis’

Daily Star online, Laura Mitchell - Anti-depressants really DO work scientists discover – but some are better than others


The Sun, p.18 - Will the pills do any good?

International Business Times UK, 23/02/2018, Yasmin Alibhai-Brown - The modern epidemic of sadness destroying heart and soul cannot be solved with anti-depressants

Xinhua News Agency (China), - Anti-depressants do help lift people’s mood, although their effects vary, according to a recent study published in the medical journal The Lancet.

Saturday 24 February 2018

Business Standard India, Antidepressants do actually work in adults: Lancet

Daily Telegraph, p.25, Bryony Gordon - I’m living proof that the drugs can work

The Guardian, p.59 - Depression: The drugs do work, say experts

Oxford Mail, p.6 - ‘A million extra’ should be using antidepressants


Monday 26 February 2018

Daily Mail (Scotland), p.16, Stephen Daisley - The drugs really do work. Without them, I wouldn’t be here today

El Pais - 


Tuesday 27 February 2018

Radio Columbia


Wednesday 28 February 2018
The Guardian – Opinion – Rhiannon Lucy Cosslett - ‘Why treating your depression is like learning your times tables’


Thursday 1 March 2018

The Guardian


Monday 5 March 2018

Radio ABC (Australian Broadcasting Corporation)


Tuesday 3 April 2018

NIHR Signal


Sunday 13 May 2013
The Mail on Sunday


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