Health reporter, BBC News
Around 3.5 million people take SSRIs every year in the UK
Antidepressants can help mild to moderate depression and should not just be used in bad cases, researchers say.
Current guidelines urge doctors to avoid antidepressants as an initial treatment in mild depression.
But an NHS-funded study of 200 patients from across England found the drugs, called SSRIs, were more effective than GP advice and support alone.
The team hope national advisers will look at their findings, reported on the Health Technology Assessment website.
Study leader Professor Tony Kendrick, a GP and researcher at the University of Southampton, said although the National Institute of Health and Clinical Excellence wants doctors to restrict SSRIs to the most severe cases, GPs frequently prescribe them for milder cases.
"Just because someone has mild depression does not mean it is a mild illness, because it can cause them to be off work for months," he said.
"And often you don't have psychological treatments to offer because they're not available so you end up prescribing quite frequently."
In the latest study, researchers looked at patients across 115 practices who had depression for at least eight weeks and had not had any counselling or drug treatment.
Half of them had usual care of four follow-up consultations with their GP over 12 weeks to talk about how they were coping and half received the same GP support plus antidepressants.
Those who had the drugs had better quality of life at the end of the trial and for every seven patients treated, one showed significant improvement by 12 weeks.
Professor Kendrick said although the benefits of the drugs were small, the results showed prescribing them for mild to moderate depression was helpful and "good value for money".
He said the findings would help GPs decide when to prescribe the drugs by assessing how long they had had symptoms and by scoring them on a depression questionnaire.
"GPs are criticised a lot for missing depression, putting too many people on antidepressants and not putting enough people on antidepressants so they can't win," he added.
Professor Andrew Tylee, an expert in primary care mental health at King's College London, who took part in the study, said the results showed that that it was often worth prescribing SSRIs for people with mild to moderate depression
"The team do hope that NICE will take this finding into account in their current revision of their depression guideline."
But Dr Tim Kendall, joint director of the National Collaborating Centre for Mental Health, threw doubt on whether the guidelines would alter.
"I think using drugs for mild to moderate depression doesn't make much sense because you're risking a lot of side effects," he said.
"Self-help approaches improve people's self-reliance."
He said the evidence base suggested psychological therapies were best in mild to moderate cases of depression and the latest research may have picked up a placebo effect.
"Access to psychological therapies has improved hugely, in Sheffield where I work GPs say there has been a noticeable difference."