What Are Selective Serotonin Reuptake Inhibitors (SSRIs)?

Selective serotonin reuptake inhibitors, or SSRIs, were the first antidepressants developed. They are now the most commonly prescribed antidepressant medications. They are prescribed to treat depression but are also used to treat a broader range of depressive disorders, anxiety disorders, and post-traumatic stress disorder (PTSD).

Having depression is common. Depression affects around 6.7% of the population (16.1 million people) of the United States each year, and that's just the people with clinical diagnoses. Medications such as SSRIs, along with other depression treatment options like talk therapy, can make depression a very treatable condition.

This article explains how SSRIs work, what conditions they are used for, and the different types you may encounter on your own mental health journey. You will also learn about the most common side effects and important safety precautions.

What Are SSRIs? 

True to their name, SSRIs are medications that inhibit or limit the reuptake of serotonin. Serotonin is the chemical messenger associated with mood, energy, sexual functioning, digestion, and sleep. It is naturally present in the gut, brain, and central nervous system.

By inhibiting the reuptake of serotonin, SSRIs work to increase levels of serotonin in your body. Low levels of serotonin are associated with depression.

Recent research also suggests that SSRIs work by changing nerve cell functioning in the brain.

Types 

FDA-approved SSRIs to treat depression, anxiety, and other mood disorders include:

• Celexa (citalopram)
• Lexapro (escitalopram)
• Luvox (fluvoxamine)
• Paxil, Paxil CR, Pexeva (paroxetine)
• Prozac (fluoxetine)
• Trintellix (vortioxetine)
• Viibryd (vilazodone)
• Zoloft (sertraline)

Not every SSRI is approved to treat every mood disorder. 

Possible SSRI Side Effects 

The FDA lists the following common side effects from SSRIs:

• Nausea
• Tremor (shaking) 
• Nervousness 
• Sleeping problems (too much or too little)
• Sexual desire or performance problems
• Sweating
• Agitation
• Fatigue 

Safety and Precautions

SSRIs may not be an option for everyone. Only you and your healthcare provider can decide what, if any, is the right antidepressant for you.

Drug Interactions

If you’re already taking other medications, SSRIs may interact with them, increasing the risk of adverse reactions or symptoms of overdose.

Negative drug interactions usually involve combinations of an SSRI with other psychotropics (psychoactive drugs that alter nervous system functions), especially tricyclic antidepressants and monoamine oxidase inhibitor (MAOI), lithium, clozapine, and methadone. Drug interactions are common with SSRIs, especially with other psychotropics.

Herbal and natural products can also cause drug interactions with SSRIs. Examples include Japanese ginkgo biloba, which can cause hemorrhaging, and ginseng, which can cause serotonin syndrome.

Serotonin Syndrome 

Serotonin syndrome is a potentially life-threatening reaction to having excessive amounts of serotonin in the nervous system. This can happen when taking SSRIs and other substances that impact serotonin known as serotonergic drugs.

Pain medications, certain migraine medications, herbal supplements (such as Saint-John's-wort), and antidepressants like SSRIs fall into this category. It causes:

• Mental status changes: This may include anxiety, restlessness, disorientation (confusion), and agitated delirium.
• Autonomic instability: Unconscious changes in nervous system function, which may include sweating, increased heart rate, high body temperature, high blood pressure, vomiting, and diarrhea.
• Neuromuscular hyperactivity: Changes in muscle activity and control, which may include tremors, involuntary muscle jerks, and overactive reflexes.

Pregnancy

SSRIs are generally considered safe during pregnancy. Untreated depression during pregnancy is not safe for the person or the growing fetus with specific neonatal needs.

Previously, there was a public health advisory for SSRIs during pregnancy due to risk of persistent pulmonary hypertension of the newborn (PPHN), which is a low concentration of oxygen in the blood due to circulation issues. That advisory has since been recalled as it was based on a single published study. Newer data show PPHN is rare, and that doctors should not alter their treatment of depression.

Children and Teens 

Antidepressants carry an FDA black box warning about a risk of increased suicidal thinking and behavior in some individuals under the age of 25.

Suicidal Thoughts 

There is risk of suicidal thinking associated with depression, mood disorders, and antidepressant use, but it's not a direct relationship, nor is it explained simply. A 2021 study demonstrated suicidal thoughts were more likely in the month before starting antidepressants than the month after or at the year-after mark. Results don’t support that SSRI treatment increases the risk of suicidal behavior, but it is possible that SSRI treatment reduces the risk.

When to Stop Treatment 

Depression, like any mental health condition, truly is different for everyone. This means there is no “standard” treatment course for antidepressants. That said, healthcare providers usually recommend taking the medication for six to nine months before deciding to go off them.

However, if you've had three or more recurrences of depression, your provider may recommend maintaining treatment for two years after your symptoms stop or stabilize. Only you and your providers can determine when or if stopping treatment is best for your situation.

How to Find the Right Antidepressant 

The right antidepressant may take trial and error to find. This is because it’s not possible to predict for certain how your body chemistry will respond to the medication.

If one SSRI doesn’t seem to be working–or the side effects are unmanageable–talk to your prescribing provider about trying another antidepressant. This can include another SSRI or another class of drugs like selective norepinephrine reuptake inhibitors (SNRIs).

Summary 

SSRIs are the most commonly prescribed antidepressants. They are used to treat depression, anxiety, and other mood disorders. There are also off-label uses. Some safety precautions exist, but this drug class is generally seen by providers as a safe choice for treating depression.

A Word From Verywell 

Depression is a complex mental health condition with many potential causes and factors that can either work in support of recovery or against treatment efforts. While medications can be a lifesaving tool for people with depression, they are not the only option, nor should they be seen as the only tool for managing depression. You may also want to consider talk therapy, which can help you work through any underlying problems (past or present).