SSRIs and SNRIs are two closely related families of antidepressants. SSRIs (selective serotonin reuptake inhibitors) act mainly on serotonin. SNRIs (serotonin and norepinephrine reuptake inhibitors) act on serotonin and norepinephrine. Both are prescribed for depression and for a range of anxiety disorders, and some are also used for other conditions.
Part of our guide: A Patient’s Guide to Psychiatric Medication
In short, both slow the rate at which nerve cells take these chemical messengers back up after release. What is less settled is exactly how that leads to feeling better. NIMH says antidepressants usually take 4 to 8 weeks to work, and that sleep, appetite, energy and concentration often improve before mood lifts.
If you are thinking about suicide or are in crisis: call or text 988 (988 Suicide & Crisis Lifeline), call 911 or go to the nearest ER.
How SSRIs and SNRIs work
Nerve cells communicate by releasing chemical messengers across a small gap. A transporter then pulls much of that chemical back into the cell, a process called reuptake. These medications block that transporter.
- SSRIs focus on serotonin. The sertraline label says the drug potentiates serotonin activity in the central nervous system by inhibiting its reuptake.
- SNRIs add norepinephrine. The venlafaxine label says its mechanism is unclear, but is thought to be related to increasing serotonin and norepinephrine activity through reuptake inhibition.
That word "unclear" matters, because FDA labels describe a likely mechanism and do not claim a complete explanation. You may have heard that depression is a simple shortage of serotonin. A 2022 umbrella review found no consistent evidence that depression is caused by lowered serotonin, and that review has been debated among researchers. It addressed the cause of depression, a separate question from whether treatment helps. A large 2018 analysis of 522 trials found that all 21 antidepressants studied worked better than placebo in the short-term treatment of adults with major depression, with varying effect sizes and tolerability.
Common medications and what the FDA label lists
Doctors may also prescribe these medications for uses outside this list. This table covers FDA-labeled uses only, and age limits vary by drug and condition.
| Medication | Family | Examples of labeled uses |
|---|---|---|
| Sertraline | SSRI | Depression, OCD, panic disorder, PTSD, social anxiety disorder, PMDD |
| Escitalopram | SSRI | Depression, generalized anxiety disorder |
| Fluoxetine | SSRI | Depression, OCD, bulimia nervosa, panic disorder |
| Citalopram | SSRI | Depression in adults |
| Paroxetine extended release | SSRI | Depression, panic disorder, social anxiety disorder, PMDD in adults |
| Venlafaxine extended release | SNRI | Depression, generalized anxiety disorder, social anxiety disorder, panic disorder in adults |
| Desvenlafaxine | SNRI | Depression in adults |
| Duloxetine | SNRI | Depression, generalized anxiety disorder, diabetic nerve pain, fibromyalgia, chronic musculoskeletal pain |
| Levomilnacipran | SNRI | Depression in adults |
How the two families differ
The main difference is the added norepinephrine effect, which carries some extra safety points. Venlafaxine's label calls for blood pressure monitoring before and regularly during treatment, and duloxetine's label warns about liver failure, sometimes fatal. Duloxetine also has labeled pain uses, which may matter to someone living with both depression and chronic pain.
This evidence does not show that either family is simply stronger. The 2018 analysis compared individual drugs, not families. Differences between drugs were smaller when all trials were counted, with wide uncertainty on most comparisons, head-to-head trials showed more variation, and tolerability varied too. Choice usually comes down to your symptoms, other health conditions, other medications, past responses and which side effects you most want to avoid. For a closer look at that decision, see how medications are determined in psychiatric treatment.
Common side effects
NIMH lists upset stomach, headache and sexual dysfunction among the common side effects of SSRIs and other antidepressants, and notes these are generally mild and tend to fade over time. Sertraline's label reports nausea, loose stools, tremor, indigestion, decreased appetite, heavy sweating and sexual side effects as its most common adverse reactions.
Sexual changes deserve a direct conversation. The sertraline label says prescribers should ask about sexual function before treatment and specifically during it, and that patients may not bring it up on their own. Raising it yourself can open up options.
Serious risks to know about
These are less common, and they are the reason follow-up visits matter.
- Boxed warning on suicidal thoughts. FDA requires a boxed warning stating that antidepressants increased the risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term studies. The sertraline Medication Guide describes the risk in some people 24 and younger, especially in the first few months of treatment or when the dose changes. All patients taking an antidepressant should be watched closely for worsening and for new suicidal thoughts. Families can help by noticing changes and calling the prescriber right away.
- Serotonin syndrome. This potentially life-threatening condition is more likely when an SSRI or SNRI is combined with other drugs that raise serotonin, including triptans, tramadol, lithium, amphetamines and St. John's Wort. Tell your prescriber about everything you take, including supplements.
- Bleeding. These medications increase the risk of bleeding events, and aspirin, NSAIDs, warfarin and other blood thinners can add to that risk.
- Mania or hypomania. In people with bipolar disorder, treating depression with an antidepressant may precipitate a mixed or manic episode. Screening for personal and family history comes first, so share any history of elevated moods.
- Low sodium. Hyponatremia can occur, and older adults and people taking diuretics may be at greater risk. Headache, confusion, weakness or unsteadiness should prompt a call.
Severe agitation, high fever, stiff muscles, fainting, seizures or confusion need urgent medical care. Do not wait for your next appointment.
What to tell your prescriber before starting
A few details can change which medication is safest for you, so bring them up even if they seem unrelated:
- Other medications and supplements. SSRIs can be dangerous with MAOI antidepressants, and the sertraline label requires at least 14 days between the two. Other labels set different gaps. Fluoxetine's calls for at least 5 weeks after stopping it before starting an MAOI.
- Any history of elevated mood, personally or in your family.
- Seizures or glaucoma. The sertraline label advises caution with a seizure disorder and says to avoid use with untreated narrow angles in the eye.
- Pregnancy or breastfeeding plans. See psychiatric medication during pregnancy.
What to expect in the first weeks
Early side effects can arrive before any benefit, which is discouraging if nobody warned you. A few practical habits help:
- Take the medication exactly as prescribed and ask what to do about a missed dose.
- Keep brief notes on sleep, energy, appetite, mood and side effects, so your clinician can see the trend.
- Ask when your first follow-up should be and how to reach the office if something feels wrong.
- Avoid judging the medication too early, and raise any worries with your prescriber rather than waiting.
- Consider therapy alongside medication. Comparing medication and therapy for depression can help you weigh that.
If several weeks pass with little change, tell your prescriber. That is useful information, and there are next steps when a medication is not working.
Stopping is a decision to make together
NIMH says people should not stop a prescribed medication without the help of a health care provider, even when they feel better. Stopping suddenly can bring on nausea, dizziness, irritability and electric shock sensations, which the labels describe as discontinuation symptoms. Make any change to your medication only with your prescriber. Our guide to discontinuation symptoms versus relapse explains how the two are told apart.
Where to go from here
If you are weighing an SSRI or SNRI, or want a second look at one you already take, medication management at Mind Body Seven covers that conversation. You can request a consultation, and the intake team confirms fit, scheduling and costs.
FAQs
Are SSRIs and SNRIs addictive?
Labels for medications such as sertraline and venlafaxine state they are not controlled substances. Stopping them can still cause discontinuation symptoms, so changes should be planned with your prescriber. The sertraline label recommends gradual reduction over abrupt stopping whenever possible.
Can teenagers take SSRIs or SNRIs?
Some are FDA-approved for young people and others are not. Escitalopram is labeled for depression from age 12 and generalized anxiety from age 7, while venlafaxine extended release is not approved for pediatric patients. The boxed warning on suicidal thoughts applies to young people in particular, so close follow-up matters, especially early on and after dose changes. Parents can learn more about medication management for teens and young adults.
Is an SNRI a better choice if an SSRI did not help?
It can be one option, though it is not automatically the better one. Your prescriber may also look at dose, how long you took the first medication, your diagnosis and whether therapy or another type of treatment makes more sense.
