The 5 Most Effective Antidepressants

The most effective antidepressants revealed by a review of 522 different studies involving 116,477 people.

The most effective antidepressants revealed by a review of 522 different studies involving 116,477 people.

Most antidepressants do work, according to a review of 522 different studies involving 116,477 people.

The review — published in the medical journal The Lancet — found that 21 common antidepressants beat placebos in strictly controlled tests.

The study’s first author, Dr Andrea Cipriani, believes this is the ‘final answer’ to the controversy over whether or not antidepressants work.

The study found that most antidepressants were better than placebo for moderate to severe depression.

However, set against this, it is well-known that common antidepressants have little to no effect for up to 50 percent of people.

5 most effective antidepressants

The five most effective antidepressants, according to this research, are:

  • Amitriptyline (known as Elavil and others)
  • Agomelatine (known as Melitor, Thymanax and Valdoxan)
  • Escitalopram (known as Cipralex, Lexapro and others)
  • Mirtazapine (known as Remeron and others)
  • Paroxetine (known as Paxil, Pexeva, Seroxat and others)

The four least effective antidepressants (although they still worked) were:

  • Fluoxetine (known as Prozac, Sarafem, Adofen and others)
  • Fluvoxamine (known as Faverin, Fevarin, Floxyfral, Dumyrox and Luvox)
  • Reboxetine (known as Edronax and others)
  • Trazodone (known as Desyrel, Oleptro, Trazorel and many others)

The study of the most effective antidepressant — known as a meta-analysis — brings together 522 different drug trials.

Some of these trials involved previously unpublished data from pharmaceutical companies.

Professor Carmine Pariante, at the London Institute of Psychiatry, who was not involved in the research, said:

“…the paper analyses unpublished data held by pharmaceutical companies, and shows that the funding of studies by these companies does not influence the result, thus confirming that the clinical usefulness of these drugs is not affected by pharma-sponsored spin.”

Professor Allan Young, Director of the Centre for Affective Disorders at London’s KCL, who was not involved in the research, said:

“…we should be aware that these findings only apply to major depressive disorder and are calculated from group data so individual patients may differ significantly in their responses.

A range of treatment choices should therefore be maintained.

Also a lot of “antidepressants” are used for other disorders (such as anxiety or OCD) or off-label (where the drug is prescribed for something other than the original condition for which it was officially approved) and this evidence does not apply in these instances.

However, the top line is that these findings should be considered good news as they confirm existing evidence that antidepressants do work and, for most people, the side-effects are worth it.”

Most of the studies involved using antidepressants for around 8 weeks — so the results don’t tell us anything about using them long-term.

They also cannot tell us which drugs are most suitable for individuals.

Are the side-effects worth it?

Although the side-effects of antidepressants are frequently pointed out, Professor Anthony Cleare at KCL (also not involved in the research) believes the benefits are worth it:

“…it is interesting that for almost all antidepressants, patients are no more likely to stop treatment early when taking an antidepressant than when taking a placebo.

Some treatments were even better tolerated than placebo.

This suggests that, overall, patients judge that the greater effect of antidepressants in relieving depression counterbalances any side effects.

Other scientists are not so sure.

For example, one review looking at antidepressants’ effect on the whole body concludes they may do more harm than good, although it may be that these ‘side-effects’ can be attributed to the underlying psychiatric conditions people are being treated for, rather than the drugs themselves.

Surveys of antidepressants side-effects also frequently find higher than expected levels of emotional numbness, sexual problems and even suicidal thoughts associated with the medication.

Indeed, it is common, in the first few weeks of treatment, for common antidepressants to cause increased anxiety and fear.

→ Read on: Antidepressants: Pros And Cons And How They Should Be Prescribed

The study was published in the journal The Lancet (Cipriani et al., 2018).


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This site is all about scientific research into how the mind works.

It’s mostly written by psychologist and author, Dr Jeremy Dean.

I try to dig up fascinating studies that tell us something about what it means to be human.

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Author: Jeremy Dean

Psychologist, Jeremy Dean, PhD is the founder and author of PsyBlog. He holds a doctorate in psychology from University College London and two other advanced degrees in psychology. He has been writing about scientific research on PsyBlog since 2004. He is also the author of the book "Making Habits, Breaking Habits" (Da Capo, 2013) and several ebooks.