The Best and Worst Antidepressants

Learn which antidepressants work best and are easiest to tolerate.

The Best and Worst Antidepressants

By Kent Peterson Published at March 5 Views 1,533 Comments 3

Kent Peterson, senior editor, has also produced award-winning work in television and radio.

Experts have long debated how well antidepressant medicines work-or whether they work at all. An international team of researchers set out to help settle the issue by reviewing hundreds of previous studies.

The good news: all of the 21 common antidepressants they studied worked better than a placebo (fake medicine). The not-so-good news: benefits of the drugs were modest. None of them provided dramatic depression relief.

Still, some medications worked better than others.

Finding the best performers

In the largest-ever study of its kind, researchers examined data from 522 double-blind, randomized controlled trials involving more than 100,000 adults with depression.

"Our study brings together the best available evidence to inform and guide doctors and patients in their treatment decisions," said study author Dr. Andrea Cipriani of Oxford University's department of psychiatry in a news release.

Some of the clinical trials they analyzed compared an antidepressant to a placebo; others pitted antidepressants against each other. Some studies had been published in scholarly journals-a measure of quality-while others had not.

Sorting the results

Of the antidepressants available in the United States, the researchers found the most effective ones included:

  • Amitriptyline
  • Effexor (venlafaxine)
  • Lexapro (escitalopram)
  • Paxil (paroxetine)
  • Remeron (mirtazapine)
  • Trintellix (vortioxetine)

Among the least effective were:

  • Luvox (fluvoxamine)
  • Oleptro (trazodone)
  • Prozac (fluoxetine)

When medicine makes you miserable

Antidepressants cause unpleasant side effects in some people. To rank which drugs were hardest to live with, the researchers investigated how many participants stopped taking their antidepressant during each study. Among the easiest medicines to tolerate:

  • Celexa (citalopram)
  • Lexapro (escitalopram)
  • Prozac (fluoxetine)
  • Trintellix (vortioxetine)
  • Zoloft (sertraline)

Less well-tolerated drugs included:

  • Amitriptyline
  • Anafranil (clomipramine)
  • Cymbalta (duloxetine)
  • Effexor (venlafaxine)
  • Luvox (fluvoxamine)
  • Oleptro (trazadone)

Only two drugs made both the most-effective list and the best-tolerated list: Lexapro and Trintellix.

Understanding the study's limitations

No study is perfect, even one as large as this. For one thing, researchers based their findings on just eight weeks of antidepressant use, so we don't know whether the rankings would change with long-term use. What's more, the authors couldn't break down group data to see if factors like age, sex, or severity of symptoms made a difference. It's also worth noting that the trials they reviewed varied in quality, and many were paid for by drug makers.

Still, this research provides important information and insights about antidepressants that we haven't had before.

Making smart decisions

If your doctor or mental health professional recommends an antidepressant, talk with him or her about these findings. But remember that individuals may respond differently to the same antidepressant. What works for one person may not work for another, so some trial-and-error may be needed.

Also, don't despair if you can't tolerate a highly ranked antidepressant. The performance differences between the studied drugs tended to be small, so you may still benefit from a medicine that was farther down the list.

Finally, bear in mind that drugs aren't the only way to treat depression. Talk therapy works well for many-sometimes in conjunction with an antidepressant, and sometimes by itself. Working with your doctor or mental health professional to find what's best for you may take time and effort-but relieving your depression is worth it.

Have you taken antidepressants? Add a comment below to tell us whether they helped and describe any side effects.

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