A huge new study may help settle the ongoing debate about whether antidepressant medications really work, concluding that all of them are effective in relieving symptoms, though some more than others.

The study, published in The Lancet, was led by researchers at Oxford Health. It reviewed 522 already-published, randomized controlled trials that tested 21 antidepressants on more than 116,000 participants.

The review concludes all the antidepressants were more effective than placebo for treating depression.

In order to be considered “effective,” the medication needed to reduce depression symptoms by 50 per cent or more by eight weeks. It also had be “acceptable,” meaning not likely to cause patients to abandon the drug by Week 8.

The study found that some medications were more effective than others. The most effective (in alphabetical order) were:

  • agomelatine (sold under several brand names, including Valdoxan, Melitor and Thymanax)
  • amitriptyline (Elavil)
  • escitalopram (Lexapro)
  • mirtazapine (Remeron)
  • paroxetine (Paxil)
  • venlafaxine (Effexor XR)
  • vortioxetine (Trintellix)

The least effective were:

  • fluoxetine (Prozac)
  • fluvoxamine (Faverin)
  • reboxetine (Edronax)
  • trazodone (Desyrel)

Dr. Sagar Parikh, a professor of psychiatry at the University of Michigan who was not involved in the study, says that given that some medications work better than others with different people, these findings will help guide doctors on which medication to try first.

“We don’t have a blood test before we take an antidepressant and so it’s a little bit hit or miss,” he explained to CTV News Channel Thursday.

“If you want to improve the odds, why not pick the ones with the best track record, the ones that really work? And this is what this study helped establish.”

He notes that of the seven most effective medications, three were also considered most tolerable, with the fewest side effects: agomelatine; escitalopram; and vortioxetine. (Agomelatine is not approved for use in Canada.)

Parikh says antidepressants can be life-changers for people with clinical depression.

“They reduce suicidality, they help them get back to work and get them functioning well with their families. So if you are able to find the right medication for the patient, it makes a dramatic difference in their day-to-day symptoms and long-term functioning,” he said.

Most of the 522 studies that the team analyzed were funded by pharmaceutical companies and thus carried a risk of bias. To try to mitigate that risk, the authors contacted pharmaceutical companies and the original study authors to ask them to provide data for studies that went unpublished. They also asked them to supplement incomplete reports from the original papers.

Dr. Andrea Cipriani, a psychiatrist at Oxford Health who was the lead author of the review as well as a researcher at the University of Oxford, says it’s important to note that while antidepressants work, for some reason, not everyone responds to them.

“Antidepressants are effective drugs, but, unfortunately, we know that about one third of patients with depression will not respond. With effectiveness ranging from small to moderate for available antidepressants, it’s clear there is still a need to improve treatments further,” Cipriani said in a statement.

The authors add that while antidepressants can be effective in treating depression, this does not mean that they should always be the first option. Medication should always be considered alongside other treatments, including psychological and psychotherapy care.