The most commonly prescribed antidepressant barely relieves symptoms of modern depression, a major study reveals.
The largest independent investigation ever undertaken found patients taking sertraline experienced negligible improvements in mood.
Published in the Lancet Psychiatry, the study comes amid mounting controversy over increased use of antidepressants by GPs in recent decades, with roughly 7.3 million people in England issued a prescription each year.
Its authors said they were “shocked and surprised” by the results, and called for the development of new classes of medication.
However, in the absence of better drugs, they do not want current prescribing practice to be changed because the trial also showed sertraline is effective in reducing anxiety, which often accompanies depression.
The new trial is by far the largest to be conducted without the involvement of the pharmaceutical industry.
It is also the most in-depth examination of sertraline – a type of selective serotonin reuptake inhibitor (SSRI) – in patients with a range of depression severities, rather than just in severely depressed patients in specialist mental health units.
The study included 654 people aged 18 to 74 who were given either the antidepressant for 12 weeks or a placebo.
The results showed depressive symptoms were five per cent lower after six weeks in the sertraline group, which was “no convincing evidence” of an effect.
After 12 weeks, there was a 13 per cent reduction, a finding the experts described as “weak”.
But the drug did offer clear benefits in reducing anxiety, with a 21 per cent reduction in symptoms at six weeks and 23 per cent at 12 weeks.
This is likely to explain why patients taking sertraline were twice as likely to say they felt generally better compared to the placebo group, even once questioned on specific symptoms of depression the benefit was far weaker.
Symptoms of depression include poor concentration, low mood, trouble with sleep, lack of enjoyment, whereas anxiety is presents as worry, nervousness, irritability and restlessness.
Professor Glyn Lewis, who led the research at University College London, said: “We were shocked and surprised when we did our analysis.
“There is absolutely no doubt this is an unexpected result.’
“Our primary hypothesis was that it would affect those depressive symptoms at six weeks and we didn’t find that.
“We definitely need better treatments for depression, and we need more research in this area.”
He suggested that new, more effective classes of antidepressants could be based on ketamine, psilocybin, the psychedelic in magic mushrooms, and anti-inflammatories.
It is thought that roughly four million people in England are long-term users of antidepressants.
Prescribing data shows that SSRI’s such as sertraline make up 54 per cent of antidepressant prescriptions.
Scientists have responded to the new study by pointing out that some of the patients had very mild symptoms of depression to start with, making it less likely that sertraline would cause an improvement.
However, others have pointed out that this is exactly the basis upon which GPs tend to hand out the drugs in practice.
Dr Gemma Lewis, who co-authored the new research, said: “I think it’s really important to understand that anxiety symptoms are very, very common among people with depression.”
She added: “It appears that people taking the drug are feeling less anxious, so they feel better overall, even if their depressive symptoms were less affected.
“We hope that we have cast new light on how antidepressants work, as they may be primarily affecting anxiety symptoms such as nervousness, worry and tension, and taking longer to affect depressive symptoms.”
Professor Helen Stokes-Lampard, Chair of the Royal College of GPs, 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.”