Do antidepressants (antidepressant medications) actually work?

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Last updated: March 18, 2025View editorial policy

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From the Guidelines

Antidepressants are effective in treating depressive disorders, particularly when selected based on adverse effect profiles, cost, and patient preferences. The American College of Physicians recommends selecting second-generation antidepressants for patients with acute major depression, considering factors such as adverse effect profiles, cost, and patient preferences 1. When choosing an antidepressant, it is essential to discuss adverse event profiles with patients, as differences have been reported among medications in terms of mild to major adverse effects, such as sexual dysfunction and suicidality.

Key considerations for antidepressant therapy include:

  • Selecting second-generation antidepressants based on adverse effect profiles, cost, and patient preferences
  • Regularly assessing patient status, therapeutic response, and adverse effects of antidepressant therapy, beginning within 1 to 2 weeks of initiation of therapy 1
  • Modifying treatment if the patient does not have an adequate response to pharmacotherapy
  • Monitoring patients for the emergence of agitation, irritability, or unusual changes in behavior, which can indicate worsening depression
  • Being aware of the increased risk for suicide attempts associated with SSRIs, particularly during the first 1 to 2 months of treatment 1

Common medications used to treat depression include:

  • Selective serotonin reuptake inhibitors (SSRIs) like fluoxetine, sertraline, and escitalopram
  • Serotonin-norepinephrine reuptake inhibitors (SNRIs) like venlafaxine and duloxetine
  • Atypical antidepressants like bupropion, which is associated with a lower rate of sexual adverse events compared to some other medications 1

It is crucial to note that antidepressants work best when combined with therapy, and patients should never stop taking them abruptly without medical supervision due to potential withdrawal effects. Treatment should continue for at least 6-12 months after symptoms improve to prevent relapse. By carefully selecting and monitoring antidepressant therapy, clinicians can help patients achieve remission and improve their quality of life.

From the FDA Drug Label

However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression

The FDA drug label indicates that antidepressants can be effective in delaying the recurrence of depression in adults, as shown by substantial evidence from placebo-controlled maintenance trials 2 and 3.

  • Key points:
    • Antidepressants can delay the recurrence of depression in adults.
    • The use of antidepressants has been shown to be effective in maintenance trials.
    • However, the labels do not provide direct evidence that antidepressants are effective in treating depression, only that they can delay its recurrence.

From the Research

Efficacy of Antidepressants

  • Antidepressants are effective in treating depression, with studies showing a significant reduction in symptoms 4, 5, 6.
  • The efficacy of antidepressants varies depending on the type and dose, with some studies suggesting that lower doses may be more effective than higher doses 4.
  • A systematic review and meta-analysis found that the response and remission rates of antidepressants were significant, with some drugs showing higher efficacy than others 6.

Factors Affecting Antidepressant Efficacy

  • The mechanism of action of antidepressants is important in determining their efficacy, with different medications affecting different symptoms and patients 7.
  • Patient preference, depressive presentation, and drug interactions should be considered when choosing an antidepressant 8.
  • A biopsychosocial and lifestyle approach should be used when managing depression, with education and shared decision-making critical components of treatment 8.

Comparison of Antidepressant Efficacy

  • A study comparing the efficacy of different antidepressants found that NASIDs, venlafaxine, and ketamine had the highest response and remission rates 6.
  • Another study found that selective serotonin reuptake inhibitors (SSRIs) were effective in treating depression, but that their efficacy varied and was incomplete 6.
  • The choice of antidepressant depends on its efficacy and tolerability, as well as patient-specific factors such as symptoms and medical history 8.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Depression in adults: drug and physical treatments.

BMJ clinical evidence, 2011

Research

Application of antidepressants in depression: A systematic review and meta-analysis.

Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 2020

Research

Why is mechanism of action important in antidepressant treatment?

The Journal of clinical psychiatry, 2016

Research

Choosing an antidepressant.

Australian prescriber, 2021

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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