The University of Hull reviewed published clinical trial data, and unpublished data secured under Freedom of Information legislation.
They found the drugs helped only a small group of the most severely depressed, and in most cases had no more effect than taking a dummy pill.
The Royal College of Psychiatrists said the findings were "very important".
In total, the Hull team, who published their findings in the journal PLoS Medicine, reviewed data on 47 clinical trials.
They focused on drugs in the class known as Selective Serotonin Reuptake Inhibitors (SSRIs), which work by increasing levels of the mood controlling chemical serotonin in the brain.
These included fluoxetine (Prozac), venlafaxine (Efexor) and paroxetine (Seroxat) - all commonly prescribed in the UK.
| || There seems little reason to prescribe anti-depressant medication to any but the most severely depressed patients |
Professor Irving Kirsch
University of Hull
The number of prescriptions for anti-depressants hit a record high in England in 2006 - even though official guidance stresses they should not be a first line treatment for mild depression.
The researchers found that even the positive effects seen on severely depressed patients were relatively small, and open to interpretation.
The seemingly good result came from the fact that these patients' response to the placebo decreased, rather than any notable increase in their response to anti-depressants.
Lead researcher Professor Irving Kirsch said: "The difference in improvement between patients taking placebos and patients taking anti-depressants is not very great.
"This means that depressed people can improve without chemical treatments.
"Given these results, there seems little reason to prescribe anti-depressant medication to any but the most severely depressed patients, unless alternative treatments have failed to provide a benefit."