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[Pharmacology](https://durgical.com/en/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)

## Key points

- Bupropion: lowers the seizure threshold; contraindicated in seizure disorders, bulimia or anorexia nervosa and abrupt withdrawal of alcohol or benzodiazepines. No sexual dysfunction; also used to stop smoking.
- Mirtazapine: sedation, increased appetite and weight gain (useful in older adults with insomnia and poor appetite); rare agranulocytosis.
- Trazodone: sedation, orthostatic hypotension and priapism (an erection lasting hours is an emergency).
- All carry the antidepressant boxed warning on suicidality in young people.

## Drugs in this class

- [**Bupropion** An antidepressant that acts on norepinephrine and dopamine, not serotonin. It also helps people stop smoking and does… Norepinephrine transporter (NET) and dopamine transporter (DAT)](https://durgical.com/en/pharmacology/bupropion/)
- [**Mirtazapine** An 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)](https://durgical.com/en/pharmacology/mirtazapine/)
- [**Trazodone** An 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)](https://durgical.com/en/pharmacology/trazodone/)

## 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.

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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](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a4c012f0-50b6-42fb-9f06-a14632f23f2e) (DailyMed (U.S. National Library of Medicine), 2026); [DailyMed - TRAZODONE HYDROCHLORIDE tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=71961ab1-951d-1493-f76c-2ff25cca2a85) (DailyMed (U.S. National Library of Medicine), 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=N06AX) (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

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Representative model, for educational purposes only.

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