Pharmacology · Class
Atypical antidepressants !
Antidepressants that work in other ways than the classic groups: bupropion, mirtazapine and trazodone. Each has its own side-effect profile.
Updated 2026-11-01
What they are
A mixed group of antidepressants whose mechanisms differ from SSRIs, SNRIs, tricyclics and MAOIs. They are chosen for their side-effect profiles: bupropion (no sexual dysfunction or weight gain, helps stop smoking), mirtazapine (sedation and appetite) and trazodone (sedation, used for sleep).
Mechanism of action
Bupropion weakly blocks the norepinephrine and dopamine transporters and has no serotonergic action. Mirtazapine blocks presynaptic alpha-2 receptors, which increases norepinephrine and serotonin release, and blocks 5-HT2, 5-HT3 and H1 receptors. Trazodone blocks 5-HT2A receptors and, more weakly, serotonin reuptake; its alpha-1 and H1 blockade explains its sedation and orthostatic hypotension.
Target: Different targets: NET and DAT (bupropion), alpha-2 adrenergic receptors (mirtazapine), 5-HT2A receptors and SERT (trazodone)
Drugs in this class
- BupropionAn antidepressant that acts on norepinephrine and dopamine, not serotonin. It also helps people stop smoking and does…Norepinephrine transporter (NET) and dopamine transporter (DAT)
- MirtazapineAn antidepressant that blocks alpha-2 receptors to release more norepinephrine and serotonin. Causes sleepiness and…Alpha-2A adrenergic receptor (also 5-HT2, 5-HT3 and H1 receptors)
- TrazodoneAn antidepressant that blocks 5-HT2A receptors and weakly blocks serotonin reuptake. Very sedating, often used for…Serotonin 5-HT2A receptor (also SERT, alpha-1 and H1 receptors)
Others in the class
- Esketamine
- Vortioxetine
- Agomelatine
- Vilazodone
Test yourself
Think of the answer, then tap the question to see it.
Which antidepressant is chosen when sexual dysfunction from an SSRI is a problem, and what is its main risk?
Bupropion, which has no serotonergic action. Its main risk is seizures, so it is avoided in seizure disorders and eating disorders.
Which antidepressant causes priapism?
Trazodone. A prolonged erection is a urological emergency, because untreated priapism can permanently damage erectile tissue.
How does mirtazapine increase norepinephrine and serotonin release?
It blocks presynaptic alpha-2 autoreceptors and heteroreceptors, removing the brake on release of norepinephrine and serotonin.
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - MIRTAZAPINE tablet, film coated (DailyMed (U.S. National Library of Medicine), 2026); DailyMed - TRAZODONE HYDROCHLORIDE tablet (DailyMed (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.