Selective serotonin reuptake inhibitors (SSRIs)

Date Updated: 09/17/2019

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants. They can ease symptoms of moderate to severe depression, are relatively safe and typically cause fewer side effects than other types of antidepressants do.

How SSRIs work

SSRIs treat depression by increasing levels of serotonin in the brain. Serotonin is one of the chemical messengers (neurotransmitters) that carry signals between brain nerve cells (neurons).

SSRIs block the reabsorption (reuptake) of serotonin into neurons. This makes more serotonin available to improve transmission of messages between neurons. SSRIs are called selective because they mainly affect serotonin, not other neurotransmitters.

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

SSRIs approved to treat depression

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

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

Possible side effects and cautions

All SSRIs are thought to work in a similar way and generally can cause similar side effects, though some people may not experience any. Many side effects may go away after the first few weeks of treatment, while others may lead you and your doctor to try a different drug.

If you can't tolerate one SSRI, you may be able to tolerate a different one, as SSRIs differ in their potencies at blocking serotonin reuptake and in how quickly the body eliminates (metabolizes) the drug.

Possible side effects of SSRIs may include, among others:

Nausea, vomiting or diarrhea
Headache
Drowsiness
Dry mouth
Insomnia
Nervousness, agitation or restlessness
Dizziness
Sexual problems, such as reduced sexual desire, difficulty reaching orgasm or inability to maintain an erection (erectile dysfunction)
Impact on appetite, leading to weight loss or weight gain

Taking your medication with food may reduce the risk of nausea. Also, as long as your medication doesn't keep you from sleeping, you can reduce the impact of nausea by taking it at bedtime.

Which antidepressant is best for you depends on a number of issues, such as your symptoms and any other health conditions you may have. Ask your doctor and pharmacist about the most common possible side effects for your specific SSRI and read the patient medication guide that comes with the prescription.

Safety issues

SSRIs are generally safe for most people. However, in some circumstances they can cause problems. For example, high doses of citalopram may cause dangerous abnormal heart rhythms, so doses over 40 milligrams (mg) a day should be avoided according to the FDA and the manufacturer. They also recommend a maximum daily dose of 20 mg of citalopram for people over age 60.

Issues to discuss with your doctor before you take an SSRI include:

Drug interactions. When taking an antidepressant, tell your doctor about any other prescription or over-the-counter medications, herbs or other supplements you're taking. Some antidepressants can interfere with the effectiveness of other medications, and some can cause dangerous reactions when combined with certain medications or herbal supplements.

For example, SSRIs may increase your risk of bleeding, especially when you're taking other medications that increase the risk of bleeding, such as nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, warfarin (Coumadin, Jantoven) and other blood thinners.
Serotonin syndrome. Rarely, an antidepressant can cause high levels of serotonin to accumulate in your body. Serotonin syndrome most often occurs when two medications that raise the level of serotonin are combined. These include, for example, other antidepressants, certain pain or headache medications, and the herbal supplement St. John's wort.

Signs and symptoms of serotonin syndrome include anxiety, agitation, high fever, sweating, confusion, tremors, restlessness, lack of coordination, major changes in blood pressure and a rapid heart rate. Seek immediate medical attention if you have any of these signs or symptoms.
Antidepressants and pregnancy. Talk to your doctor 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 breast-feeding. If you're taking an antidepressant and you're considering getting pregnant, talk to your doctor about the possible risks. Don't stop taking your medication without contacting your doctor first, as stopping might pose risks for you.

Suicide risk and antidepressants

Most antidepressants are generally safe, but the FDA requires that all antidepressants carry black box 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, especially 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, immediately contact your doctor or get emergency help.

Keep in mind that antidepressants are more likely to reduce suicide risk in the long run by improving mood.

Stopping treatment with SSRIs

SSRIs aren't addictive. However, stopping antidepressant treatment abruptly or missing several doses can cause withdrawal-like symptoms. This is sometimes called discontinuation syndrome. Work with your doctor to gradually and safely decrease your dose.

Withdrawal-like symptoms can include:

General feeling of uneasiness
Nausea
Dizziness
Lethargy
Flu-like symptoms

Finding the right antidepressant

People may react differently to the same antidepressant. For example, a particular drug 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.

Inherited traits play a role in how antidepressants affect you. If you have a close relative who responded to a particular antidepressant, tell your doctor, because this could be a good drug choice to start.

In some cases, results of special blood tests, where available, may offer clues about how your body may respond to a particular antidepressant. However, other variables can affect your response to medication.

When choosing an antidepressant, your doctor takes into account your symptoms, any health problems, other medications you take and what has worked for you in the past.

Typically, it may take several weeks or longer before an antidepressant is fully effective and for initial side effects to ease up. Your doctor may recommend some dose adjustments or different antidepressants, but with patience, you and your doctor can find a medication that works well for you.