Atypical antidepressants explained
Antidepressants that work differently from SSRIs and SNRIs, and when they are used.
What "atypical" means
"Atypical antidepressants" is not a tidy category. It is a loose label for antidepressants that do not fit the two big classes, the SSRIs and the SNRIs. The medications grouped under it work in different ways from one another, so the term describes what they are not more than what they share. The most useful way to understand them is one by one.
How they work
In short, atypical antidepressants act on different chemical messengers, or in different ways, than SSRIs do. Some work mainly on norepinephrine and dopamine. Some affect serotonin through more complex routes. The mechanism is specific to each drug, so the individual medication pages on PsychiatryRx are the place to look for detail.
When they're used
Atypical antidepressants are often used when an SSRI or an SNRI is not the right fit. That can happen because of side effects, or because the first medication only partly helped. Having a group of medications that work differently gives a prescriber different trade-offs to work with, which is useful when a standard option has not done the job.
The medications in this group
- Bupropion (Wellbutrin). Works on norepinephrine and dopamine rather than serotonin. It is activating, it rarely causes sexual side effects, and it tends not to cause weight gain. It carries a dose-related seizure risk. It is often chosen for people who want to avoid sexual side effects or weight gain.
- Mirtazapine (Remeron). Tends to be sedating and to increase appetite. It is often chosen when depression comes with serious insomnia and loss of appetite.
- Trazodone (Desyrel). At low doses it is mostly used as a sleep aid. At higher doses it can act as an antidepressant.
- Vortioxetine (Trintellix) and vilazodone (Viibryd). Newer medications that act on serotonin in more complex ways than a standard SSRI.
What they have in common
The medications in this group differ a great deal, but they still share a couple of things. They usually take several weeks for the fuller effect, as other antidepressants do. They also carry the same antidepressant boxed warning about a possible increase in suicidal thoughts in people under 25, especially early in treatment.
Sources
This guide draws on current prescribing information and public health references. It is reviewed for clinical accuracy and updated as guidance changes.
- U.S. Food and Drug Administration. Prescribing information.
- MedlinePlus, U.S. National Library of Medicine.
- National Institute of Mental Health. Mental health medications.
This guide is for general education. It is not medical advice and is not a substitute for evaluation, diagnosis, or treatment by a qualified clinician. Never start, stop, or change a medication without talking to your prescriber. If you are in crisis or thinking about harming yourself, call or text 988 in the U.S. to reach the Suicide and Crisis Lifeline.