Antidepressant Classes Compared: SSRIs, SNRIs, Bupropion, Mirtazapine and Older Options
Short answer
Most antidepressants prescribed today fall into a few groups: SSRIs, SNRIs, bupropion and mirtazapine, with older tricyclics and MAOIs used less often. FDA labels describe different likely mechanisms and different common side effects, but the labels reviewed here all carry the same boxed warning about suicidal thoughts in young people. No class suits everyone. A prescriber weighs your symptoms, health, other medicines and past responses.
In crisis or thinking about suicide? Call or text 988 now (in New York City it reaches NYC 988). If you are in immediate danger, call 911.
This guide is not enough if
- You are thinking about suicide or harming yourself. Call or text 988, or call 911 if you are in danger now.
- You want to switch or stop an antidepressant you already take. Talk with your prescriber first; do not change it on your own.
- You need a dose or a recommendation for one specific drug. This guide compares classes at a general level only.
- You have signs of a serious reaction such as fever, a racing heartbeat, muscle stiffness, confusion or a seizure. Get medical help right away.
Why the class matters, and why it is not the whole decision
Maybe a prescriber has suggested a medicine and you want to know what kind it is. Or you tried one antidepressant, it did not fit, and you want to understand what else exists. Knowing the class helps you follow the conversation and ask better questions.
Class is only part of the picture, though. MedlinePlus says the newer types are usually tried first and the older types may cause more serious side effects, and that some people need to try two or more medicines before finding one that works. FDA labels are also frank about uncertainty: several say a drug's mechanism is unclear or unknown.
For a deeper look at the two most common groups, see SSRIs and SNRIs explained. This guide puts all the main classes side by side.
What the classes have in common
Each label reviewed for this guide (sertraline, venlafaxine, bupropion, mirtazapine, amitriptyline and phenelzine) carries a boxed warning: antidepressants increased the risk of suicidal thoughts and behaviors in children, teens and young adults in short-term studies, and all patients should be watched closely for worsening. What a boxed warning means explains how to read that warning.
They also share a timeline. NIMH says antidepressants usually take 4 to 8 weeks to work, which how long antidepressants take to work covers in detail. And none should be combined with an MAOI: the sertraline, venlafaxine, mirtazapine and bupropion labels each rule out use while taking an MAOI or within 14 days of stopping one.
Two more shared warnings are worth knowing before a first visit. The sertraline, venlafaxine, bupropion and mirtazapine labels all tell prescribers to screen for bipolar disorder before starting, because an antidepressant can trigger mania or hypomania, so mention any personal or family history of unusually high or elevated moods. The same four labels warn that angle-closure glaucoma has occurred in people with untreated narrow angles in the eye who took antidepressants, so mention any eye conditions too.
| Class (label example) | How the label says it may work | Common side effects on the label | Key safety points |
|---|---|---|---|
| SSRIs (sertraline) | Raises serotonin activity by blocking its reuptake | Nausea, diarrhea, tremor, indigestion, sweating, sexual side effects | Serotonin syndrome with other serotonergic drugs; bleeding risk with NSAIDs or blood thinners |
| SNRIs (venlafaxine) | Thought to raise serotonin and norepinephrine activity | Nausea, sleepiness, dry mouth, sweating, sexual side effects | Blood pressure checks before and during treatment; serotonin syndrome |
| Bupropion | Unknown; presumed norepinephrine and dopamine effects, no serotonin reuptake blocking | Dry mouth, nausea, insomnia, dizziness, agitation, anxiety | Dose-related seizure risk; not for seizure or eating disorders; can raise blood pressure |
| Mirtazapine | Unclear; may raise norepinephrine and serotonin activity through alpha-2 receptor blocking | Sleepiness, increased appetite, weight gain, dizziness | Serious drop in white blood cells (seen in a few trial patients): report fever, sore throat or infection |
| Older classes: tricyclics (amitriptyline) and MAOIs (phenelzine) | Older drugs with broader effects | Tricyclics: dry mouth, constipation, blurred vision, trouble urinating | Tricyclics: heart rhythm changes reported; MAOIs: tyramine diet rules and many drug interactions |
SSRIs and SNRIs
SSRIs act mainly on serotonin. The sertraline (Zoloft) label says the drug increases serotonin activity in the brain by blocking its reuptake. Its most common side effects in trials included nausea, diarrhea, tremor, indigestion, decreased appetite, heavy sweating and sexual side effects.
SNRIs add norepinephrine. The venlafaxine (Effexor XR) label says its action is thought to come from increasing serotonin and norepinephrine activity through reuptake inhibition. Common side effects on that label include nausea, sleepiness, dry mouth, sweating and sexual side effects. The label also says to control high blood pressure before starting and to monitor blood pressure regularly.
Both groups can raise the risk of bleeding, especially with aspirin, NSAIDs or blood thinners, according to the sertraline label. Sexual side effects deserve a direct conversation; sexual side effects and weight changes covers options.
Bupropion and mirtazapine: two that work differently
Bupropion (Wellbutrin) is not an SSRI. Its label says the mechanism is unknown but presumed to involve norepinephrine and dopamine, and that it does not block serotonin reuptake. Common side effects include dry mouth, nausea, trouble sleeping, dizziness, agitation and anxiety. It can also raise blood pressure.
Its key warning is seizures. The label says seizure risk is dose-related, and bupropion is not to be used by people with a seizure disorder, a current or past eating disorder (bulimia or anorexia), or who are abruptly stopping alcohol, benzodiazepines or certain other drugs.
Mirtazapine (Remeron) is also different. Its label says the mechanism is unclear but may involve blocking certain alpha-2 receptors, which raises norepinephrine and serotonin activity. The most common side effects were sleepiness, increased appetite, weight gain and dizziness. The label also warns about agranulocytosis, a serious drop in infection-fighting white blood cells seen in a few patients in its clinical trials, so a sore throat, fever or other sign of infection needs a prompt call.
Tricyclics and MAOIs: older options with more rules
Tricyclic antidepressants (TCAs) include amitriptyline. Its label lists anticholinergic effects such as dry mouth, constipation, blurred vision and trouble urinating. It says tricyclics, particularly at high doses, have been reported to cause heart rhythm changes, and that people with heart conditions should be watched closely.
MAOIs, such as phenelzine (Nardil), have the most rules. The phenelzine label warns that foods high in tyramine, such as aged cheeses, dry sausage, beer and wine, can trigger a dangerous rise in blood pressure (a hypertensive crisis). It also lists many medicines that should not be combined with it, including stimulants and the cough medicine dextromethorphan. NIMH notes that older antidepressants have more side effects but may still be the right option for some people.
Interactions that cut across classes
Some interaction risks apply to several classes at once. Bring a full list of what you take to every medication visit.
- Serotonin syndrome. The sertraline label says SSRIs and SNRIs can bring on this potentially life-threatening condition, and the risk rises with other serotonergic drugs such as triptans, tricyclics, tramadol, lithium, amphetamines, tryptophan and St. John's wort.
- MAOI combinations. Mixing an MAOI with another antidepressant can be dangerous; labels require a waiting period when switching.
- Supplements. NCCIH says St. John's wort can interact in dangerous, sometimes life-threatening ways with many medicines. See supplements and mental health.
- Alcohol. Advice varies by drug. The sertraline Medication Guide, for example, says not to drink alcohol while taking it.
- Pill changes. If a refill looks different, a generic may have been swapped in; brand vs generic explains when to mention it.
When comparing classes is not the right next step
If you are having thoughts of suicide, set this comparison aside. Call or text 988, or call 911 if you are in immediate danger; crisis and hotline resources has more options.
If your current medicine is not helping, do not switch or stop on your own. The sertraline label notes that stopping, especially abruptly, can cause symptoms such as dizziness, irritability and anxiety. How switching antidepressants works explains what a planned change involves, and questions to ask before starting a psychiatric medication helps you prepare. If several medicines have not helped, read about depression and treatment-resistant depression care or medication management.
Frequently asked questions
Which antidepressant class has the fewest side effects?
There is no single answer. FDA labels list different common side effects for each class, such as sexual side effects with SSRIs, trouble sleeping with bupropion, and sleepiness and weight gain with mirtazapine. Which matters most depends on you, your other health conditions and your other medicines. Tell your prescriber which side effects you most want to avoid so the choice can account for them.
Is bupropion an SSRI?
No. The bupropion label says its mechanism is unknown but presumed to involve norepinephrine and dopamine, and that it does not inhibit the reuptake of serotonin. That is one reason its side effect profile differs from SSRIs. It carries its own warnings, including a dose-related seizure risk, and it shares the boxed warning about suicidal thoughts in young people that antidepressants carry.
Why would a prescriber suggest an older antidepressant like an MAOI?
NIMH says older antidepressants such as tricyclics and MAOIs have more side effects but may still be the right option for some people. MAOIs come with diet rules about tyramine-rich foods and a long list of drug interactions, so they need careful planning and clear instructions. If one is suggested, ask what the food and medicine rules are and what to do if you need another prescription or a cold medicine.
Can I switch from one class to another on my own?
No. Switching needs a plan from your prescriber. Labels for sertraline, venlafaxine, mirtazapine and bupropion rule out use with an MAOI or within 14 days of stopping one, and stopping some antidepressants quickly can cause symptoms such as dizziness and irritability. Your prescriber can decide whether to taper, overlap or wait between medicines, based on the specific drugs involved.
Next: get ready to decide
A question list for the medication conversation, with why each question matters and where the answer is written down.
Sources
- DailyMed: Zoloft (sertraline) label
- DailyMed: Effexor XR (venlafaxine) label
- DailyMed: Wellbutrin XL (bupropion) label
- DailyMed: Remeron (mirtazapine) label
- DailyMed: Nardil (phenelzine) label
- DailyMed: amitriptyline hydrochloride tablets label
- NIMH: Mental Health Medications
- MedlinePlus: Antidepressants
Reviewed by Dr. Beata Lewis, MD, Founder and Clinical Director, board-certified in adult psychiatry, child and adolescent psychiatry, and integrative medicine on November 8, 2026. Facts checked against the sources above on November 8, 2026. This guide is general education, not medical advice, a diagnosis or a treatment plan, and reading it does not make you a patient of Mind Body Seven. For advice about your situation, talk with a licensed clinician.