Study Shows Zoloft and Lexapro the Best of Newer Antidepressants

Patient Expert

Several new medications for the treatment of depression have been introduced over the last 20 years. What has been missing is any consistent data about the effectiveness of these "second-generation" antidepressants.

A team of researchers have now reviewed 117 controlled trials to compare second-generation antidepressants for the acute treatment of unipolar major depressive disorder in adults. The medications were reviewed for efficacy (effectiveness), patient acceptability, and cost.

Study methods:

  • Researchers reviewed 117 controlled trials of second-generation antidepressants.
  • These trials had a total of 25,928 participants.
  • The antidepressants compared were:
    • bupropion (Wellbutrin/Zyban)
    • citalopram (Celexa)
    • duloxetine (Cymbalta)
    • escitalopram (Lexapro)
    • fluoxetine (Prozac)
    • fluvoxamine (Luvox)
    • milnacipran (Savella)
    • mirtazapine (Remeron)
    • paroxetine (Paxil)
    • reboxetine (Edronax)
    • sertraline (Zoloft)
    • venlafaxine (Effexor)
  • Medications were judged by the proportion of patients who responded well to the medications or discontinued the medications.
  • Researchers defined "acute" treatment as an eight-week treatment period. When eight-week data were not available, the utilized data ranting from six- to 12-week periods.

Study findings:

  • Mirtazapine, escitalopram, venlafaxine, and sertraline were significantly more effective than duloxetine, fluoxetine, fluvoxamine, paroxetine, and
  • Reboxetine was significantly less effective than all the other antidepressants studied.
  • Escitalopram and sertraline showed the best profile of acceptability, which caused them to have significantly fewer discontinuations than did duloxetine, fluvoxamine, paroxetine, reboxetine, and venlafaxine.

Study interpretation:

This paragraph from the journal abstract summarizes the researcher's interpretation of the data and their conclusions:

"Clinically important differences exist between commonly prescribed antidepressants for both efficacy and acceptability in favour of escitalopram and sertraline. Sertraline might be the best choice when starting treatment for moderate to severe major depression in adults because it has the most favourable balance between benefits, acceptability, and acquisition cost."

The bottom line:

Escitalopram (Lexapro) and sertraline (Zoloft) came out on top when reviewed for effectiveness and patient acceptability. Sertraline (Zoloft) has the advantage of being available in generic, whereas no generic is available yet for Lexapro.

Reboxetine (Edronax) came out on the bottom of the pile in all comparisons.

Individual responses to medications vary greatly. Your experience with any of these medications may not match those of the trial outcomes. Still, if you and your doctor are considering which medications to try, these results are worth keeping in mind.


Cipirani, Andrea; Furukawa, Toshiaki A.; Salant, Georgia; Higgins, Julian P.T.; Churchill, Rachel; Watanabe, Norio; Nakagawa, Atsuo; Omori, Ichiro M.; McGuire, Hugh; Tansella, Michele; Barbui, Corrado. "Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis." The Lancet, Early Online Publication, 29 January 2009

Kahn, Michael. "Zoloft, Lexapro best new antidepressants: study." Reuters. January 28, 2009.

HealthDay News. "Zoloft, Lexapro the Best of Newer Antidepressants." January 29, 2009.