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Antidepressants ‘more effective than placebo’ for acute depression in adults

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Antidepressants are more effective than placebo for the short-term treatment of acute depression in adults, a study led by UK researchers has confirmed.

They noted that there was “considerable debate” about the effectiveness of antidepressants, which were used more frequently than psychological interventions because of inadequate resources.

“We found that the most commonly used antidepressants are more effective than placebo”

Andrea Cipriani

Their new meta-analysis of 522 trials carried out between 1979 and 2016, and which involved a total of 116,477 participants and compared 21 commonly used antidepressants.

They concluded that all the drugs were 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The international study, published in The Lancet, used the largest amount of unpublished data to date, all of which has now been made freely available online.

The authors identified all double-blind, randomised controlled trials comparing antidepressants with placebo, or with another antidepressants, for the acute treatment of major depression in adults.

They 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study authors, and regulatory agencies to supplement incomplete reports of the original papers, or provide data for unpublished studies.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 – and acceptability – proportion of patients who withdrew from the study for any reason by week eight.

“This study represents the best currently available evidence base to guide the choice of pharmacological treatment”

John Ioannidis

Some antidepressants were found to be more effective than others, with the majority of the most effective ones now off patent and available in generic form, noted the researchers.

Those that were least effective were fluoxetine, fluvoxamine, reboxetine, and trazodone being the least effective, according to the researchers.

Meanwhile, they said agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine proved most effective.

The researchers also highlighted that antidepressants differed in terms of acceptability to patients, though only clomipramine was less acceptable than placebo.

Those drugs found to be the least tolerable were amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine.

In contrast, the study authors said the most tolerable were agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine.

However, the authors noted that the data included in the meta-analysis covered eight weeks of treatment, so may not necessarily apply to longer term antidepressant use.

They 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.

The authors noted they did not have access to individual-level data so were only able to analyse the antidepressants in relation to age, sex, symptom severity, illness duration or other characteristics.

But they highlighted that their latest findings contrasted with their previous analysis in children and adolescents, also published in The Lancet, which indicated fluoxetine was the only antidepressant that might reduce depressive symptoms.

They suggested the difference may partly be because depression in young people was the result of different mechanisms or causes.

Lead author Dr Andrea Cipriani, from University of Oxford, said the study brought together the “best available evidence to inform and guide” treatment decisions.

University of Oxford

Major review reveals most and least effective antidepressants

Andrea Cipriani

“We found that the most commonly used antidepressants are more effective than placebo, with some more effective than others,” he noted.

“Our findings are relevant for adults experiencing a first or second episode of depression – the typical population seen in general practice,” he said.

Dr Cipriani highlighted that, while antidepressants could be an “effective tool” to treat major depression, it did not necessarily mean they should always be the first line of treatment.

“Medication should always be considered alongside other options, such as psychological therapies,” noted Dr Cipriani, who is also a consultant psychiatrist at Oxford Health NHS Foundation Trust.

“With effectiveness ranging from small to moderate for available antidepressants, it’s clear there is still a need to improve treatments further,” he added.

Co-researcher Professor John Ioannidis, from Stanford University in the US, said: “This study represents the best currently available evidence base to guide the choice of pharmacological treatment for adults with acute depression.”

The study was funded by the National Institute for Health (NIHR) Research Oxford Health Biomedical Research Centre and the Japan Society for the Promotion of Science.

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