Does the effectiveness of antidepressant medications increase with depression severity?

Updated: Aug 06, 2020
  • Author: Jerry L Halverson, MD; Chief Editor: David Bienenfeld, MD  more...
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In a meta-analysis, Fournier et al found that medication superiority over placebo increased with increases in baseline depression severity, crossing the threshold for a clinically significant difference at a baseline Hamilton Depression Rating Scale (HDRS) score of 25. [119] In patients with mild or moderate depression, antidepressant medication had minimal or no benefit compared with placebo, but in patients with very severe depression, antidepressant drugs provided a substantial benefit compared with placebo.

More confirmation that antidepressants work for depression came from a large meta-analysis of 522 randomized controlled trials that compared 21 different antidepressants with placebo in more than 116,000 patients with major depressive disorder. [120] The 21 antidepressants included in the trials were agomelatine, amitriptyline, bupropion, citalopram, clomipramine, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, trazodone, venlafaxine, vilazodone, and vortioxetine. Results showed that each studied antidepressant was significantly more efficacious, defined as yielding a reduction of at least 50% in the total score of a standardized scale for depression, than placebo after 8 weeks. Patients who received agomelatine, escitalopram, and vortioxetine had both high response rates and low dropout rates. [120]

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