What Are Selective Serotonin Reuptake Inhibitors (SSRIs)?

Close up of Prozac, Paxil and Zoloft antidepressant tablets
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What Are Selective Serotonin Reuptake Inhibitors (SSRIs)?

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed class of antidepressants in the United States. Developed in the 1970s, SSRIs are the first class of medication prescribed for depression.

This article describes what SSRIs are and how they work, lists common brand names, and identifies which conditions SSRIs treat. You will learn the common side effects of SSRIs and precautions to consider before taking them.

How SSRIs Work

The function of SSRIs is actually described in its name—selective serotonin reuptake inhibition. Serotonin is a naturally occurring substance in the body known as a neurotransmitter. It's also known as the "feel good" chemical. Serotonin is found in the brain, central nervous system (CNS), and other parts of the body.

Serotonin has a number of functions including mood regulation, memory, sleep, sexual function, and digestion, among others. While serotonin is linked with feelings of happiness, low levels of serotonin are linked to mood disorders like depression.

SSRIs work by blocking the reabsorption, or reuptake, of serotonin and increasing the amount of serotonin in the brain. Increasing serotonin in the brain is linked with regulating anxiety, mood, and promoting a greater sense of well-being.

Common Brand Names

The following are brand names of some of the SSRIs that are currently FDA-approved to treat depression, anxiety, and other mood disorders:

FDA-Approved Uses

In addition to treating depression, SSRIs are FDA-approved to treat the following mental health conditions in adults, including:

SSRIs are also the first-line medication option for young people with depression and anxiety. The table below lists the FDA-approved uses for individual SSRIs.

  For Children For Adults
Celexa MDD
Lexapro MDD GAD, MDD
Paxil GAD, MDD, OCD, PD, PTSD, SAD
Prozac MDD, OCD MDD, OCD, PD
Trintellix MDD
Viibryd MDD
Zoloft OCD MDD, OCD, PD, PMDD, PTSD, SAD

As you can see, not every SSRI is FDA-approved to treat every mood-related disorder.

Off-Label Uses

If a doctor prescribes a medication for a purpose other than what it has been approved to treat, this is called "off-label" prescribing. For example, Paxil and Zoloft are the only SSRIs approved by the FDA for PTSD, but doctors may prescribe Prozac off-label to treat PTSD.

Prescribing a drug off-label can mean prescribing a drug for:

  • A different age range: Treating children with a medication that has been approved for use in adults only
  • A different condition: When a medication is used for a condition that it is not approved to treat
  • At a different dosage: When a medication is dosed differently than what has been approved

Off-label use does not imply illegal use. In fact, the practice is legal and quite common. According to one study, one in five prescriptions is written for off-label use.

Doctors may also prescribe SSRIs off-label to treat a broad range of other conditions, including eating disorders, fibromyalgia, migraines, and premature ejaculation.

Precautions and Contraindications

SSRIs are not for everyone and must be used with caution in certain individuals. Be sure you speak to a doctor thoroughly about any preexisting conditions you may have before starting an SSRI.

Pregnancy

Hundreds of studies have looked at SSRI exposure and birth defects. With the exception of Paxil, most SSRIs are generally considered safe to use during pregnancy. But they are not without risk. Although rare, the following are risks that have been linked to SSRI use during pregnancy:

  • Birth defects: SSRI use during pregnancy may increase the risk of abdominal, heart, and lung birth defects.
  • Blood loss after childbirth: Some studies have reported a slightly higher risk of postpartum hemorrhage among women on SSRIs.
  • Miscarriage or premature birth: A person who is pregnant and taking antidepressants is at increased risk for a number of complications, including miscarriage and premature delivery.
  • Psychiatric disorders in children: Children of pregnant people who used antidepressants before and during pregnancy have a higher risk of developing a psychiatric disorder. However, this association may be attributable to the severity of the parent’s underlying condition.
  • Withdrawal symptoms in newborns: Newborns exposed to SSRIs in the last trimester may experience withdrawal symptoms. The most common withdrawal symptoms are tremors, disturbed sleep, and high-pitched crying.

Letting depression go untreated can also have a negative impact on a pregnancy. Remember to always discuss your specific situation thoroughly with a doctor before discontinuing any medication.

Breastfeeding

It's possible that SSRIs can be passed to your baby through your breastmilk. If you're pregnant (or trying to become pregnant) and wish to breastfeed, try to choose an antidepressant that is safe to use both during pregnancy and breastfeeding. 

Zoloft, Paxil, and Prozac have been widely studied and are considered relatively safe for use during breastfeeding. The data suggest that the amount of these drugs nursing infants are exposed to is low enough that there are no adverse effects.

Children

In 2004, the FDA issued a black box warning—the agency's strictest warning—that young people (up to age 25) taking antidepressants might experience increased suicidal thoughts and behaviors.

The warning also says that children and adolescents taking SSRIs should be carefully watched for sudden changes in their mood or actions, such as:

If you see any of these signs in your child, particularly if they are new or noticeably worse than before, be sure to talk to a doctor as soon as possible.

If your child is having suicidal thoughts, contact the National Suicide Prevention Lifeline at 1-800-273-8255 for support and assistance from a trained counselor. If you or a loved one are in immediate danger, call 911.

For more mental health resources, see our National Helpline Database.

Side Effects

SSRIs are considered the most effective antidepressants with the fewest side effects. The majority of people who take them, however, do experience at least one side effect. Most of them are minor and usually go away as your body gets used to the medication.

Common side effects of most SSRIs include:

  • Diarrhea
  • Drowsiness
  • Dry mouth
  • Headache
  • Increased sweating
  • Insomnia
  • Nausea and vomiting
  • Sexual dysfunction (delayed or absent orgasm and decreased libido)
  • Weight gain

Consult with a doctor so they can explain all the known side effects of your chosen SSRI. If you're experiencing one or more of these side effects, let a doctor know. They may be able to suggest ways to lessen the effects or adjust your dose as needed.

Serotonin Syndrome

SSRIs aren't the only medications that increase serotonin levels in your body. Other medications, such as certain pain medications, certain migraine medications, and herbal supplements (such as St. John's wort), can also increase serotonin levels.

Taking two or more of drugs that increase serotonin levels in your body (also known as serotonergic drugs) can lead to a condition called serotonin syndrome.

Serotonin syndrome can also occur if you are taking two or more antidepressants—for example, taking an SSRI and a selective norepinephrine reuptake inhibitor (SNRI) or an SSRI and monoamine oxidase inhibitor (MAOI).

If too much serotonin builds up in your body, you may experience some of the following symptoms of serotonin syndrome:

  • Autonomic effects: Abnormally fast heart rate, hypertension, hyperthermia, shivering, sweating
  • Mental status effects: Confusion, delirium, excitement, restlessness, and hallucinations
  • Neuromuscular effects: Muscle twitching, tremor, and increased reflexes

Though rare, serotonin syndrome may be life-threatening if not treated immediately.

Before starting any medication, it is important that you discuss all the medications you're taking with a doctor to avoid developing serotonin syndrome. You should also use caution when increasing doses of an SSRI.

Discontinuation Syndrome

SSRIs work by altering the levels of neurotransmitters, which are the chemical messengers that attach to neurons throughout the body and influence their activity.

Neurons eventually adapt to the new level of neurotransmitters. But if the level changes too much too quickly—for example, because you've suddenly stopped taking your antidepressant—it can lead to uncomfortable withdrawal symptoms such as:

  • Feeling anxious
  • Flu-like symptoms
  • Hyperarousal
  • Nausea
  • Sensory disturbances
  • Trouble sleeping

Symptoms occur within two to four days after drug cessation and usually last one to two weeks.

As many as one in five people who stop an antidepressant quickly may experience at least a mild version of discontinuation syndrome. 

Paroxetine is linked with the highest incidence of discontinuation syndrome, whereas fluoxetine is linked with the lowest. In general, lower doses of SSRIs are associated with fewer occurrences of discontinuation syndrome.

Treatment for discontinuation syndrome depends on your individual symptoms, which SSRI you were taking, and your dosage. Recommendations for potentially lessening symptoms include tapering gradually off your dosage instead of stopping immediately as well as switching from your current SSRI to the more slowly metabolized fluoxetine.

Discontinuation syndrome is not life-threatening and symptoms should subside within a few weeks. Talk to a doctor before discontinuing your medication; they can help you develop a strategy to hopefully minimize any symptoms.

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