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

SSRIs generally cause fewer side effects than other treatments, which is one reason they’re the most commonly prescribed antidepressants.

Medically Reviewed

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.

In fact, SSRIs are the most commonly prescribed class of antidepressants — they’re generally the first choice over other types of antidepressants because they’re fairly safe and often cause fewer side effects.

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.

Many people experience depression — approximately 16.1 million adults in the United States.

 But because of antidepressants like SSRIs, as well as other modalities like talk therapy, depression is one of the most treatable mental illnesses.

How Do SSRIs Work?

Experts don’t know exactly how SSRIs work. One effect these drugs are believed to have is by increasing the body’s supply of certain neurotransmitters, or chemicals that nerve cells in the brain use to communicate with one another.

 One such chemical, serotonin, exists in the brain as well as other parts of the body and helps regular functions like sleep, mood, and appetite.
Recent research also suggests that SSRIs may enhance how nerve cells in the brain function.

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).

Common SSRIs

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:

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Common Side Effects of SSRIs

SSRIs typically pose fewer side effects than other types of antidepressants. Common side effects of SSRIs include:

  • 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.

Sexual dysfunction — difficulty becoming sexually aroused, maintaining an erection, or reaching sexual climax — is another common side effect, especially among younger folks, says Carroll. SSRIs may cause sexual dysfunction in 40 to 65 percent of people, which in some cases could exacerbate depressive symptoms and make it more difficult for someone to stick to their treatment regimen.

Rare Side Effects of SSRIs

SSRIs can have other rare but serious side effects, such as internal bleeding. In addition, the FDA requires that SSRIs carry a black box warning — the strictest possible warning — because they may be associated with an elevated risk of suicidal thoughts or behaviors among children, teens, and young adults under age 25, especially within the first few weeks of treatment or if the dose is altered.

Approximately 4 percent of people who take SSRIs experience suicidal thoughts. However, experts say this risk must be balanced with the serious suicide risk posed by untreated depression.

Furthermore, a 2020 study by experts at Harvard University and the University of Pennsylvania raised questions about whether the FDA’s black box warnings about antidepressants may do more harm than good. In the study, the researchers linked the establishment of the black box warning with a decline in depression treatment and increase in suicide rates among adolescents and young adults. They mentioned that other factors may have contributed to this trend, but based on their findings, they urged additional research to determine the potential effects of the black box warning.

SSRI Withdrawal and Discontinuation Syndrome

SSRIs aren't addictive like other substances such as tobacco. You won’t experience cravings for these medications if you stop taking them. But going off an SSRI abruptly — or missing several doses in a row — may cause what’s known as antidepressant 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.

Typical Duration of Treatment

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.”

Recent Research on the Effectiveness of SSRIs

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.

In fact, research shows that not all antidepressants are equally effective and appropriate for all people. This means that while SSRIs may be helpful and even life-changing for some people, they may not be as suitable as other antidepressants for other people.

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.

Experts have also studied ways to maximize the benefits of antidepressants like SSRIs. Ample research shows that antidepressant treatment may be most effective when combined with talk therapies such as cognitive behavioral therapy — in which individuals learn to replace unhelpful thought and behavior patterns with healthier ones — among adults with depression.

Contraindications: Who Shouldn’t Take an SSRI?

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.

People using certain medications or supplements may be unable to take an SSRI due to potential drug interactions. These medications include:

  • 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.

Off-Label Uses for SSRIs

When doctors prescribe a medication “off-label,” this means they’ve prescribed the drug for a use they deem medically appropriate for a certain patient, but this use has not been formally approved by the FDA.

Off-label prescriptions are not uncommon. One study published in February 2017 showed that, out of more than 100,000 antidepressant prescriptions, nearly one-third were for an off-label use such as pain, migraine, or insomnia.

The most common off-label use for SSRIs is anxiety — in fact, SSRIs are considered the first-choice medication for many types of anxiety.

“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.

SSRIs and Pregnancy

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.

In some cases, it might slightly increase the risk of birth defects. For example, while most research found no link between taking SSRIs such as citalopram or sertraline during pregnancy and an increased risk of birth defects, the SSRI paroxetine was shown to slightly increase the risk of a fetal heart defect. For this reason, experts typically discourage the use of paroxetine during pregnancy.

Additionally, about 30 percent of babies whose mothers are treated with SSRIs will develop neonatal adaptation syndrome. Potential symptoms include increased irritability, jitteriness, and difficulty breathing. Experts believe this may be due to either the baby experiencing withdrawal from the SSRI or exposure to SSRIs before birth. These symptoms will eventually go away, but your baby’s pediatrician may opt to run some medical tests just to be safe.

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.”

SSRIs and Breastfeeding

SSRI treatment among breastfeeding women has been well studied. Experts believe that they’re relatively safe for use during breastfeeding.

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

SSRIs and COVID-19

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.

In one November 2021 study, researchers assessed the health records of more than 83,500 patients who’d been diagnosed with COVID-19 between January and September 2020, including about 3,400 patients taking SSRIs. The study showed that people taking SSRIs, especially fluoxetine, had a significantly reduced risk of dying compared with people who weren’t taking SSRIs. The researchers note that large-scale studies are still needed to confirm these findings.

Editorial Sources and Fact-Checking

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