The pills were expected to have a changing effect on depressive symptoms such as poor concentration, insomnia and low mood, but the results were damning.
The medication did however boost the overall mood in patients through reduction of anxiety, and as a result, patients reported feeling better after taking them than those given a placebo.
"WE NEED BETTER TREATMENTS"
Researcher Professor Glyn Lewis, head of division at UCL Psychiatry, said: "We were shocked and surprised when we did our analysis. There is absolutely no doubt this is an unexpected result.
"Antidepressants work but perhaps in a different way to the way we had originally thought.
"They seem to be working on anxiety symptoms first before any smaller, and later, possible effects on depression.
"We definitely need better treatments for depression."
Sertraline is part of most common class of antidepressant known as selective serotonin reuptake inhibitors (SRI).
The study, published in The Lancet Psychiatry, was conducted in GP surgeries across England.
It included 653 people experiencing depressive symptoms, who were split into two groups.
The first group was given a dummy drug for 12 weeks while the second group was given sertraline.
After six weeks, those on the active pills experienced a five per cent improvement in depressive symptoms compared to the placebo. After 12 weeks the gain was just 13 per cent.
However, experts found the pills did ease anxiety symptoms. These include worry, nervousness, irritability and restlessness.
WHERE TO GET HELP:
If you are worried about your or someone else's mental health, the best place to get help is your GP or local mental health provider. However, if you or someone else is in danger or endangering others, call 111.
If you need to talk to someone, the following free helplines operate 24/7:
DEPRESSION HELPLINE: 0800 111 757
LIFELINE: 0800 543 354
NEED TO TALK? Call or text 1737
SAMARITANS: 0800 726 666
YOUTHLINE: 0800 376 633 or text 234
There are lots of places to get support. For others, click here.