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Atypical antidepressants, including bupropion (Wellbutrin), mirtazapine (Remeron), nefazodone (Serzone), trazodone (Desyrel), and vilazodone (Viibryd), offer unique mechanisms of action. Bupropion weakly inhibits dopamine and norepinephrine reuptake, aiding depression treatment and smoking cessation, with a low risk of sexual dysfunction. Mirtazapine enhances serotonin and norepinephrine neurotransmission, leading to sedation, increased appetite, and weight gain. As a result, it helps treat...
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Related Experiment Video

Updated: Feb 5, 2026

Network Pharmacology and Validation of the Antidepressant Mechanisms of Qiangzhifang in a Chronic Restraint Stress-induced Depression Rat Model
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Other Antidepressants.

T E Schwasinger-Schmidt1, M Macaluso2

  • 1Department of Internal Medicine, University of Kansas School of Medicine-Wichita, Wichita, KS, USA. tschwasinger-schmidt@kumc.edu.

Handbook of Experimental Pharmacology
|September 9, 2018
PubMed
Summary
This summary is machine-generated.

This chapter reviews five unique FDA-approved antidepressants: bupropion, mirtazapine, trazodone, vortioxetine, and vilazodone. These medications offer distinct mechanisms of action for treating major depressive disorder, targeting various central nervous system receptors.

Keywords:
BupropionMirtazapineTrazadoneVilazodoneVortioxetine

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Area of Science:

  • Pharmacology
  • Neuroscience
  • Psychiatry

Background:

  • Major depressive disorder (MDD) is a prevalent mental health condition.
  • Existing antidepressant classes do not encompass all treatment needs.
  • Novel mechanisms of action are crucial for effective MDD management.

Purpose of the Study:

  • To provide a comprehensive overview of five FDA-approved antidepressants not fitting major classes.
  • To detail the unique pharmacology, efficacy, and safety profiles of bupropion, mirtazapine, trazodone, vortioxetine, and vilazodone.
  • To highlight their distinct mechanisms targeting central nervous system receptors for MDD treatment.

Main Methods:

  • Review of FDA-approved medications for MDD in the United States.
  • Analysis of unique structures and properties targeting diverse central nervous system receptors.
  • Examination of indications, development history, pharmacology, metabolism, dosing, onset of action, special populations, safety, tolerability, adverse effects, interactions, and overdose data.

Main Results:

  • Bupropion uniquely targets norepinephrine and dopamine without affecting serotonin.
  • Mirtazapine enhances norepinephrine and serotonin via alpha-2 antagonism.
  • Trazodone acts as a 5-HT2A/2C antagonist and SSRI, also used for insomnia.
  • Vortioxetine combines serotonin transporter inhibition with 5-HT1A receptor modulation.
  • Vilazodone is an SSRI and 5-HT1A partial agonist, offering potentially reduced sexual side effects.

Conclusions:

  • These five antidepressants offer unique mechanisms distinct from major classes.
  • They target diverse central nervous system receptors, providing alternative treatment options for MDD.
  • Their efficacy and remission rates are comparable to SSRIs, often with improved tolerability and specific symptom targeting.