Selective Serotonin Reuptake Inhibitors (SSRIs)

SSRIs are medications used to treat several mental health conditions. Here we profile the usage, benefits and risks of SSRIs for the treatment of depression and anxiety.

Selective serotonin reuptake inhibitors, known more commonly as SSRIs, are among the most commonly prescribed medications in the world. As more information has become available about these drugs, the public has become more informed about how SSRIs can treat depression and anxiety.

What are SSRIs?

SSRIs are the most commonly prescribed medications of a larger class of drugs called antidepressants. As the name of this class suggests, SSRIs are used for the treatment of depression, though they also help treat several other conditions. As a class of medications, SSRIs are the second most widely prescribed class of medications in the world behind the statins class of cholesterol-lowering drugs.

Along with serotonin-norepinephrine reuptake inhibitors (SNRIs), SSRIs are part of the second generation of antidepressants. These medications are known for having good safety profiles and for being well tolerated by patients. This differentiates them from older antidepressants such as monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs), which can have several problematic side effects and are sometimes not well tolerated.

Background and History

Though the quest to find drugs that improve mood is as old as human history, it wasn’t until the 1950s that antidepressants as we know them became a subject of laboratory research. At the time, scientists were trying to find treatments for tuberculosis, but one candidate drug was shown to improve the mood and the outlook in people who took it.

This research led to the development of the monoamine hypothesis — the idea that neurotransmitters like serotonin, dopamine and norepinephrine were responsible for conveying information about mood, anxiety levels and general happiness. This research led to the development of the first generation of antidepressant medications — the MAOIs.

The history of SSRIs branches off in the 1970s, when the pharmaceutical company Eli Lilly began using research about the role of serotonin availability in depression to create new compounds. As a result, the molecule fluoxetine (later known as Prozac) emerged as a prime candidate, and the development of the first SSRI was underway. Prozac was approved by the United States Food and Drug Administration (FDA) for the treatment of depression in 1987, and it became the first SSRI on the market.

Use in Treating Mental Illness

SSRIs are commonly prescribed for the treatment of depression and anxiety disorders. SSRIs are FDA approved for the treatment of the following conditions:

• Major depressive disorder
• Generalized anxiety disorder
• Panic disorder
• Social phobia
• Obsessive-compulsive disorder
• Premenstrual dysphoric disorder

SSRIs are now the gold standard of treatment and are commonly prescribed for moderate and severe levels of anxiety and depression.

How Do SSRIs Work?

So what do SSRIs do that allows them to be utilized for so many different conditions? How do SSRIs work in the brain to treat anxiety and depression? The brain’s nerve cells use serotonin as a communicator about mood, anxiety level and overall well-being. The cells “talk” with each other by varying the amount, location and rate of serotonin released from one nerve cell to another.

SSRIs amplify the amount of serotonin available to communicating cells by preventing serotonin from getting reabsorbed by the cell that initially sends the message. This is called reuptake inhibition — the “RI” in “SSRI” — and it allows more serotonin to be available to the cell receiving the message.

Over time, this process helps improve mood and decrease anxiety. The “selective” part of an SSRI refers to the fact that these medications have little effect on other neurotransmitters, such as dopamine or norepinephrine.

Types of SSRIs

This list of SSRIs shows medications with FDA approval to treat depression and/or anxiety, as of early 2019. Different types of SSRIs are often used for different purposes; for example, paroxetine and sertraline are commonly used for anxiety disorders because of their high potency.

• Citalopram (Celexa): A mid-potency, moderately selective SSRI
• Escitalopram (Lexapro): A mid-potency moderately selective SSRI chemically similar to citalopram
• Fluoxetine (Prozac): The most selective SSRI
• Fluvoxamine (Luvox): A more potent, shorter-acting SSRI
• Paroxetine (Paxil): The most potent SSRI
• Sertraline (Zoloft): A more potent, longer-acting SSRI
• Vilazodone (Viibryd): A relatively newer SSRI with fewer sexual side effects

Effectiveness of SSRIs

Numerous studies have questioned if SSRIs are effective. Decades of research have indicated that SSRIs are no more or no less effective than other antidepressants. However, they are prescribed more often than other antidepressants because they are better tolerated and have fewer side effects.

Side Effects of SSRIs

Although SSRIs are generally well-tolerated, they do have several well-known potential side effects. SSRI side effects can include:

• Nausea
• Vomiting
• Diarrhea
• Headache
• Drowsiness
• Agitation or restlessness
• Sexual dysfunction
• Sensory changes

Risks Associated with SSRIs

Among the most significant risks associated with the SSRI medication class is the link between SSRIs and serotonin syndrome. Serotonin syndrome is characterized by:

• Temperature elevation
• Mental status changes
• Flushing
• Sweating
• Tremor
• Agitation
• Increased reflexes
• Diarrhea

Serotonin syndrome is more likely to develop while using an SSRI and another serotonergic medication, such as an SNRI like Effexor, or with some opioids, like tramadol. In addition to serotonin syndrome, SSRIs are also associated with hyponatremia (low sodium balance in the bloodstream), especially when taken with diuretic medications.

Rarely, SSRIs can also trigger suicidal thoughts or behaviors, especially in teenage or young adult patients. Finally, SSRI medications can trigger mania in someone with bipolar disorder if they are taken (fluoxetine appears to be somewhat of an exception, and it is FDA approved to treat bipolar depression when taken with olanzapine).

Possible Interactions

Despite their relative safety, SSRIs can and do interact with other medications. SSRI drug interactions with negative clinical consequences usually involve the combination of an SSRI with other mental health medications, such as the first generation antidepressants (MAOIs and TCAs) clozapine and lithium. Opioids can combine with SSRIs to cause heart rhythm disturbances (for example, taking citalopram and methadone together is generally not recommended because of this possibility).

Taking SSRIs While Pregnant

Using antidepressants during pregnancy has benefits as well as risks. They help protect against the potential effects of depression on pregnancy, including improper prenatal care, suicidal thoughts and behaviors, poor eating habits and more.

On the other hand, some SSRIs can increase the risk of birth defects. For example, paroxetine (Paxil) is generally discouraged: It has been shown in two studies to increase fetal risk for right-sided heart defects. Most clinicians feel that the benefits of SSRIs outweigh their relatively minor risks of birth defects, and research data also appears to support this opinion.

If a woman wishes to know if she can take an SSRI while pregnant, she should consult with her OB/GYN provider or with a psychiatrist. They can help assess whether the benefits of taking SSRIs outweigh the risks of not taking them.

Note: Before 2015, SSRIs except for paroxetine were classified by the FDA as pregnancy class C. This classification meant that animal research demonstrated a link to minor fetal damage when taking the drug, but human research was inadequate or inconclusive. The FDA now utilizes narrative information rather than a class letter, but the outdated pregnancy classes labeling system is still seen on health information websites.

Stopping SSRIs

A unique feature of SSRIs, compared to other commonly prescribed medications, is that they should be tapered (gradually decreased). The action of SSRIs creates biochemical remodeling in the brain and body, which need time to readapt their usual functions.

In theory, fluoxetine (Prozac) does not need a taper because of its long half-life. Most still recommend tapering for all SSRIs. One danger of stopping SSRIs abruptly is that it can lead to a withdrawal-like antidepressant discontinuation syndrome, characterized by:

• Sensory changes
• Nausea
• Restlessness
• Fatigue
• Weakness

What to Do In Case of Overdose

Like all overdoses, SSRI overdoses are medical emergencies. If an SSRI overdose is intentional, it is a psychiatric emergency as well. Emergency medical services such as 911 should be activated if an SSRI overdose is suspected. Even though SSRIs are considered safe, and an overdose of only SSRIs without other medications is not usually fatal, SSRI overdose can lead to serotonin syndrome and other health risks.

Get More Information on SSRIs

SSRIs may be a treatment option for anyone who suffers from depression or anxiety disorders. The Recovery Village has articles and personnel that can help you make choices about your treatment.

If you or someone you care about would like more information about SSRIs, depression or anxiety, The Recovery Village can help. Our network of resources about mental health conditions and substance use disorders and our staff of professionals can guide your decisions about which medications to use and how to go about managing these conditions. Call or chat with us today.

Editor – Jonathan Strum

Jonathan Strum graduated from the University of Nebraska Omaha with a Bachelor's in Communication in 2017 and has been writing professionally ever since. Read more

Medically Reviewed By – Dr. Kevin Wandler, MD

Kevin Wandler holds multiple positions at Advanced Recovery Systems. In addition to being the founding and chief medical director at Advanced Recovery Systems, he is also the medical director at The Recovery Village Ridgefield and at The Recovery Village Palmer Lake. Read more