All About Selective Serotonin Reuptake Inhibitors (SSRIs): Types, Side Effects, and More

What do Prozac, Lexapro, and Zoloft have in common? All belong to a class of drugs called selective serotonin reuptake inhibitors, or SSRIs, and all have been approved by the U.S. Food and Drug Administration (FDA) to treat depression and related mental health conditions.

They’re also more accessible and cost-effective than other treatment options for depression, says James Rachal, MD, a psychiatrist and senior academic chairman of the department of psychiatry at Atrium Health in Charlotte, North Carolina.

Even though SSRIs all belong to the same class of drugs, they don’t work exactly the same way, says Dr. Rachal. That’s why an SSRI that’s effective for one person might not work as well for someone else, and it might cause different side effects for different people. And if an SSRI doesn’t work for you, this doesn’t mean you have to give up on treatment. There are other options, such as selective norepinephrine reuptake inhibitors (SNRIs), norepinephrine and dopamine reuptake inhibitors (NDRIs), tricyclic antidepressants, and monoamine oxidase inhibitors (MAOIs).

In 1987, fluoxetine (Prozac) was the first SSRI to be approved by the FDA. It became the most popular drug at the time for depression because it was well-tolerated and effective, says Andrew J.P. Carroll, MD, a family physician based in Chandler, Arizona, and a member of the board of directors of the American Academy of Family Physicians. Prozac is still commonly used to treat depression.

The other FDA-approved SSRIs are:

• Citalopram (Celexa)
• Escitalopram (Lexapro)
• Paroxetine (Paxil)
• Sertraline (Zoloft)

• Agitation, nervousness, or restlessness
• Diarrhea
• Dizziness
• Drowsiness or insomnia
• Dry mouth
• Headache
• Nausea or vomiting
• Reduced sexual desire or sexual performance
• Weight gain or loss due to appetite changes

Weight gain is one of the most common side effects of SSRIs, but the amount gained varies from person to person, says Dr. Carroll. “One to three pounds in one person might be 10 to 20 pounds in another,” he says.

That said, not all weight gain is necessarily caused by the SSRI itself. For example, some people with severe depression may have lost weight before treatment due to loss of appetite, a common symptom of depression, Carroll explains. But once the treatment helps their appetite return to normal, they may gain that weight back later on.

Rare Side Effects of SSRIs

SSRI Withdrawal and Discontinuation Syndrome

Symptoms include:

• Anxiety
• Dizziness
• Flu-like symptoms
• Headache
• Irritability
• Lethargy
• Nausea
• Return of depressive symptoms
• Sensations resembling electric shocks
• Vivid dreams or insomnia

Antidepressant discontinuation syndrome can usually be avoided by reducing your dose gradually (also known as tapering) to allow your body to adjust.

There is no typical treatment course for SSRIs. The ideal length of treatment has not been well studied, and in practice how long someone will need to take an SSRI varies from person to person. Doctors often prescribe SSRIs in accordance with evidence-based treatment guidelines, which account for factors like depression severity and how each person’s mind and body respond to treatment.

For instance, Carroll says that when he prescribes SSRIs to patients experiencing their first episode of depression, he periodically checks to see how they’re adjusting to the medication and whether they’re experiencing any uncomfortable side effects. Once the patient is stabilized — meaning their depressive symptoms have receded — he generally advises they continue taking the SSRI for at least another six months.

If someone’s depressive symptoms return after their first round of treatment ended, both Carroll and Rachal recommend their patients take an SSRI daily for at least one year.

In general, says Carroll, people who can function normally and don’t have suicidal thoughts or behaviors can eventually taper off SSRIs, or gradually stop taking them under the supervision of their doctor. However, Rachal adds, “There are some people who will experience multiple episodes of depression or persistent symptoms without remission, and for them, we recommend staying on the SSRI indefinitely.”

Although SSRIs have been studied in clinical research trials for decades, findings related to their safety and effectiveness vary. Although many studies show SSRIs can work very well, it's difficult to predict exactly how each individual will react to these medications, mentally and physically, especially when it comes to side effects, says Carroll.

Thus, the effectiveness of SSRIs is most often measured on an individual basis based on improvements in one’s depression compared with any side effects one experiences, Carroll explains. This helps you and your doctor determine whether an SSRI is the best treatment option for you.

People with bipolar disorder often need to avoid SSRIs because these drugs are associated with an increased risk of manic episodes among people with this condition. However, for someone with bipolar disorder who has been stabilized with a mood-stabilizing drug like lithium (Eskalith, Eskalith-CR, Lithobid, Lithonate, Lithotabs) or lamotrigine (Lamictal), treatment with an SSRI might benefit them, Carroll notes.

• Aspirin, warfarin, blood thinners, and other medications that increase risk of bleeding, because SSRIs have been linked to an increased risk of bleeding.
• Medications or supplements that contain serotonin, such as St. John’s wort. If you take too many substances containing serotonin, you may develop a rare but serious medical emergency called serotonin syndrome, evidenced by symptoms like fast heartbeat, significant changes in blood pressure, high fever, sweating, and confusion, among others. This can occur in people taking more than one antidepressant or certain headache or pain medications such as triptans.

  

As always, if you are prescribed an SSRI, be sure to tell your doctor about any other supplements or medications you’re taking and before taking any new ones.

“SSRIs may reduce the frequency and severity of migraine headaches, and decrease nerve pain associated with diabetes,” adds Rachal.

In some cases, SSRIs can also be prescribed off-label to treat premature ejaculation, say Rachal and Carroll.

Talk to your doctor about the benefits and risks of taking an SSRI during pregnancy. Antidepressant use during pregnancy is generally safe, but it’s not without risk.

The decision to continue or discontinue an SSRI while pregnant largely depend on one’s functioning, says Carroll. For instance, he explains, if one of his patients is taking a low-dose SSRI for mild depression and considering becoming pregnant, he says he’d likely help that patient safely taper off the medication.

“If you're not suicidal and you are functional, less substances in your system throughout pregnancy is better,” Carroll says.

But for someone with moderate to severe depression, it may be safer to continue taking an antidepressant. “Some studies have shown untreated depression and anxiety during pregnancy can also have effects on the development of the baby while in the womb, as well as effects on mother-baby bonding after the child is born,” explains Rachal. “So, it is important to weigh the risk and benefit of any medication with your healthcare provider.”

Nevertheless, if you’re breastfeeding, talk to your doctor about the risks and benefits of taking an SSRI during this time.

Another potential benefit of SSRIs is they may have protective effects against some of the most severe COVID-19 symptoms, including death, emerging research suggests.