Selective serotonin reuptake inhibitors (SSRIs)

Date Updated: 09/11/2024

Selective serotonin reuptake inhibitors, also called SSRIs, are the type of antidepressant prescribed most often. They can ease symptoms of moderate to severe depression. They are relatively safe, and they typically cause fewer side effects than other types of antidepressants do.

How SSRIs work

Serotonin is one of many chemical messengers in the brain called neurotransmitters. Neurotransmitters carry signals between nerve cells in the brain, called neurons.

After carrying a signal between brain cells, serotonin usually is taken back into those cells, a process called reuptake. But SSRIs block this process. Blocking reuptake makes more serotonin available to help pass messages between brain cells. SSRIs are called selective because they mainly affect serotonin, not other neurotransmitters.

SSRIs may be used to treat conditions other than depression, such as anxiety disorders.

SSRIs approved to treat depression

The U.S. Food and Drug Administration (FDA) has approved these SSRIs to treat depression:

Citalopram (Celexa).
Escitalopram (Lexapro).
Fluoxetine (Prozac).
Paroxetine (Paxil).
Sertraline (Zoloft).

Possible side effects and cautions

All SSRIs are thought to work in much the same way. They generally can cause many of the same side effects. But some people have no side effects. Many side effects may go away after the first few weeks of treatment. Some side effects may lead you and your healthcare professional to try a different medicine.

If one SSRI doesn't work well for you, a different one may work better. This is because SSRIs differ in how well they block serotonin reuptake and in how quickly they break down and are cleared from the body.

Possible side effects of SSRIs may include:

Upset stomach, vomiting or diarrhea.
Sweating.
Headache.
Sleepiness or trouble sleeping.
Dry mouth.
Nervousness, anxiety or restlessness.
Shakiness.
Sexual problems, such as lessened sexual desire, trouble reaching orgasm or trouble getting and keeping an erection.
Changes in appetite, leading to weight loss or weight gain.

Taking your medicine with food may lessen the risk of an upset stomach. Also, so long as your medicine doesn't keep you from sleeping, taking it at bedtime may lessen an upset stomach.

The antidepressant that is best for you depends on several factors, such as your symptoms and any other health conditions you may have. Ask your healthcare professional and pharmacist about the side effects that are most common for the SSRI prescribed for you. Also read the patient medicine guide that comes with the prescription.

Safety issues

SSRIs are generally safe for most people. But some can cause safety issues. For example, citalopram can cause dangerous irregular heart rhythms if the dose is too high. The FDA and the manufacturer recommend that the dose should be no more than 40 milligrams (mg) a day, but no more than 20 mg of citalopram a day for people over age 60.

Before you take an SSRI, talk with your healthcare professional about:

Interactions with other medicines and supplements. When taking an antidepressant, tell your healthcare professional about any other prescription or nonprescription medicines, herbs, or other supplements you're taking. Some antidepressants can interfere with the effectiveness of other medicines. Some antidepressants can cause dangerous reactions when combined with certain medicines or herbal supplements.

For example, SSRIs may raise your risk of bleeding. The risk is higher when you also take other medicines that raise the risk of bleeding, for example, a nonsteroidal anti-inflammatory drug, such as aspirin or ibuprofen (Advil, Motrin IB, others), or warfarin (Jantoven) and other blood thinners.
Serotonin syndrome. Rarely, an antidepressant can cause high levels of serotonin to build up in your body. Serotonin syndrome most often occurs when two medicines that raise the level of serotonin are combined. These include, for example, other antidepressants, some pain or headache medicines, and the herbal supplement St. John's wort.

Symptoms of serotonin syndrome include anxiety, being nervous or jittery, high fever, sweating, confusion, shaking, restlessness, lack of coordination, major changes in blood pressure, and a fast heartbeat. Get medical help right away if you have any of these symptoms.
Antidepressants and pregnancy. Talk to your healthcare professional about the risks and benefits of using specific antidepressants. Some antidepressants may harm your baby if you take them during pregnancy or while you're breastfeeding. If you're taking an antidepressant and you're thinking about getting pregnant, talk with your healthcare professional about the possible risks. Don't stop taking your medicine without talking with your healthcare professional first, as stopping puts you at risk.

Suicide risk and antidepressants

Most antidepressants are generally safe. But the FDA requires that all antidepressants carry boxed warnings, the strictest warnings for prescriptions. In some cases, children, teenagers and young adults under 25 may have an increase in suicidal thoughts or behavior when taking antidepressants. This may be more likely in the first few weeks after starting or when the dose is changed.

Anyone taking an antidepressant should be watched closely for worsening depression or unusual behavior. If you or someone you know has suicidal thoughts when taking an antidepressant, call your healthcare professional right away or get emergency help.

Keep in mind that depression that's not treated is a more concerning risk of suicide. And antidepressants may lessen suicide risk in the long run by improving mood for many people.

Stopping treatment with SSRIs

SSRIs aren't habit-forming. However, stopping antidepressant treatment suddenly or missing several doses can cause withdrawal-like symptoms. This is sometimes called discontinuation syndrome. Work with your healthcare professional to slowly and safely lower your dose.

Withdrawal-like symptoms can include:

Restlessness and anxiety.
Nausea.
Dizziness.
Feeling sluggish or sleepy.
Flu-like symptoms, such as chills, sweating and muscle aches.

Finding the right antidepressant

Different people may react differently to the same antidepressant. For example, one medicine may work better — or not as well — for you than for another person. Or you may have more, or fewer, side effects from taking a specific antidepressant than someone else does.

Traits passed down in your family play a role in how antidepressants affect you. If a relative responded well to a particular antidepressant, tell your healthcare professional. This may be a good medicine for you to try first.

In some cases, results of special blood tests, where available, may offer clues about how your body may respond to a particular antidepressant. But other factors can affect your response to medicine. For example, people with a history of bipolar disorder typically aren't given SSRIs for depression. That's because SSRIs may worsen their symptoms.

When choosing an antidepressant, your healthcare professional considers your symptoms, any health conditions you may have, other medicines you take and what has worked for you in the past.

It may take several weeks or more before an antidepressant is fully effective and for early side effects to ease up. Your healthcare professional may recommend some dose changes or different antidepressants. With patience, you and your healthcare professional can find a medicine that works well for you.