SSRI vs SNRI for Depression: What the Labels Say

What the two groups have in common

SSRIs and SNRIs are two of the three antidepressant groups the National Institute of Mental Health (NIMH) calls commonly prescribed. In its account, both help across many depressive and anxiety disorders, with fewer side effects than older types.

Their labels also share much of the same safety information. This includes the boxed warning about suicidal thoughts and behaviors in children, teens and young adults, serotonin syndrome, increased bleeding risk, activation of mania or hypomania, symptoms after stopping, angle-closure glaucoma and low sodium. Both groups must not be combined with MAOIs, the labels say. If you are in crisis, call or text 988, or call 911. Locascio Wellness does not provide emergency services.

How each is thought to act

The difference is in the names. SSRI stands for selective serotonin reuptake inhibitor. The sertraline label says it increases serotonin activity in the central nervous system by blocking serotonin reuptake, and that it has only very weak effects on norepinephrine and dopamine reuptake.

SNRI stands for serotonin and norepinephrine reuptake inhibitor. The labels for venlafaxine and desvenlafaxine say the way each treats depression is unclear or unknown, but is thought to relate to boosting serotonin and norepinephrine by blocking reuptake. A difference in action is a documented fact about the medicines, and it does not show that one group works better.

Labeled uses, medicine by medicine

What a medicine is FDA-approved for comes from its own label, and medicines in the same group can differ a lot. These examples come from current labels.

• Sertraline (Zoloft), SSRI: major depressive disorder, obsessive-compulsive disorder, panic disorder, posttraumatic stress disorder, social anxiety disorder and premenstrual dysphoric disorder.
• Escitalopram (Lexapro), SSRI: major depressive disorder in adults and in young people 12 and older, and generalized anxiety disorder in adults and in children 7 and older.
• Venlafaxine extended-release (Effexor XR), SNRI: adults with major depressive disorder, generalized anxiety disorder, social anxiety disorder and panic disorder. Not approved for pediatric patients.
• Desvenlafaxine (Pristiq), SNRI: adults with major depressive disorder. Not approved for pediatric patients.
• Levomilnacipran (Fetzima), SNRI: major depressive disorder in adults.

Side effects listed on the labels

Each label lists the most common side effects seen in its studies. The lists overlap, and trials differ, so these are not a head-to-head comparison.

• Sertraline: nausea, diarrhea or loose stool, tremor, indigestion, decreased appetite, sweating, ejaculation failure and decreased sex drive.
• Escitalopram: insomnia, ejaculation disorder, nausea, increased sweating, fatigue, sleepiness, decreased sex drive and difficulty with orgasm.
• Venlafaxine extended-release: nausea, sleepiness, dry mouth, sweating, abnormal ejaculation, loss of appetite, constipation, impotence and decreased sex drive.
• Desvenlafaxine: nausea, dizziness, insomnia, sweating, constipation, sleepiness, decreased appetite, anxiety and specific male sexual problems.
• Levomilnacipran: nausea, constipation, sweating, increased heart rate, erectile dysfunction, ejaculation disorder, vomiting and pounding heartbeat.

One documented difference: blood pressure

The labels for venlafaxine, desvenlafaxine and levomilnacipran each have a warning about elevated blood pressure and say it should be monitored during treatment. The sertraline and escitalopram labels do not have a warning section on this. The levomilnacipran label also has a warning about raised heart rate.

This matters mainly for people who have high blood pressure or heart concerns, so mention those to any prescriber. A warning like this describes something to watch for, and it does not make a medicine a right or wrong choice for you. That judgment takes your whole health picture.

Working it out with us

A licensed psychiatrist on our team, a Doctor of Osteopathic Medicine with more than three decades of practice, offers online depression treatment by secure video for people physically located in Pennsylvania or New York during each visit. Whether either group is an option for you is a decision for you and your prescriber. Ask us whether our psychiatrist can help, using our medication care contact form.

If you take one of these medicines now, please do not stop or change it on your own: reactions can occur when these medicines are stopped, and the labels advise reducing them gradually. Our therapists do not prescribe. They see clients in Pennsylvania, West Virginia, Arizona, Colorado and Florida, not New York.