Despite claims that antidepressants may be just delivering a placebo effect, three-quarters of people who tried them in a large study said they helped
Antidepressants are one of the most commonly used medicines, but they don’t work for everyone.
Now a large real-world study, published in the journal Psychological Medicine, has identified the groups of people who are least likely to find them helpful – which includes men and older people.
The research used an ongoing health study called UK Biobank, where people were asked if they had ever taken a kind of antidepressant called an SSRI – the Prozac class of drugs – and whether it helped them. Nearly 20,000 people were included.
About three-quarters of people said that antidepressants had helped them “at least a little”.
As well as men and older people being less likely to report a benefit, the study found that “non-responders” were likely to have a lower income, to use alcohol or illegal drugs to boost their mood, and to have been depressed for over two years.
Mood lifting
Another risk factor linked with a lower chance of benefiting from the medicines was if people did not usually get a lift in mood from positive events.
Conversely, people were more likely to have found that antidepressants helped them if they were women, were younger, had a higher income, if they didn’t use alcohol or illegal drugs to improve their mood, and if they had not been depressed for long.
The study did not investigate why these factors were linked with people’s odds of responding, and we should not assume the factors were directly causing the response, said Professor Cathryn Lewis, a geneticist at King’s College London (KCL). “We don’t know whether this is cause or effect,” she said.
But people who are drinking excess alcohol or taking illegal drugs might not benefit from antidepressants because they are missing doses, said Professor Lewis.
Alcohol can also make people feel more depressed, even though people often think it will improve their mood.
Another risk factor for poor response to antidepressants was a genetic variant that makes the liver less effective at breaking down the medicines – this might lead to higher antidepressant levels, raising the risk of side effects.
The relatively high number of people who said they were helped by the medicines was welcomed by Professor Peter Tyrer, a psychiatry researcher at Imperial College London, who was not involved in the research. “To get a 75 per cent positive response is a very important finding,” he said.
The results are similar to those from previous small randomised trials of antidepressants, but such trials tend to involve only people in good general health, with less complex mental conditions, he said. “Trials don’t actually look at the variation within the population. A big advantage of these large-scale studies is that they can.”
Antidepressants have come in for criticism in recent years, with independent analyses of drug company trial results suggesting they cause only small improvements in mood compared with people in comparison groups taking placebo tablets.
“The use of antidepressants, and the rate at which they are prescribed in the UK, has been the source of much debate,” said Dr Michelle Kamp, a postdoctoral research associate at KCL. “This research provides reassuring evidence that many people report that this common type of medication is helping them manage what can be a severe illness.”
Placebo effect
But Professor Joanna Moncrieff, a psychiatrist at University College London who has previously criticised the growing use of antidepressants, said depression is particularly responsive to the “placebo effect” – when symptoms improve simply because people expect them to.
“This was not a test of response [to antidepressants]. This was a test of what people think about their antidepressants,” she said. “We know that most people who respond to an antidepressant will also respond to a placebo.”
Professor Moncrieff said that this could also explain some of the “risk factors” that predicted non-response. “Some of the things they’ve found suggest that these are just markers of a more severe condition – like lower income,” she said.
“People who have milder conditions will get better anyway, and will therefore feel that the antidepressant has helped them. People who have more severe conditions may not get better and will therefore feel that the antidepressant hasn’t helped.”
A spokesperson for the Royal College of Psychiatrists said: “Most patients will benefit from the use of antidepressants, but as with all medications, some people have side effects or negative experiences, which is why their use should be carefully monitored and regularly reviewed.
“We would advise anyone thinking of stopping their antidepressant to talk to their doctor first, as these medications should not be stopped abruptly.”