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SSRI Antidepressants: Types, Uses & Risks

SSRIs (selective serotonin reuptake inhibitors) such as Prozac, Paxil and Zoloft revolutionized the treatment of depression and related disorders when they arrived on the market in the 1980s. But research has found that SSRIs can cause serious side effects ranging from withdrawal complications to birth defects to suicidal thoughts and behavior in younger patients.

Last Modified: January 26, 2024
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Eleven percent of Americans aged 12 years and over take an antidepressant medication, according to the Centers for Disease Control and Prevention.

The use of antidepressants increased nearly 400 percent between 1988 and 2008. As of 2022, SSRIs are the most common class of antidepressants in the U.S. and are believed to be safer and generally cause fewer side effects than other antidepressants.

SSRIs are prescribed to treat depression, anxiety disorders, panic attacks and personality disorders. They have been shown to be more effective in severe cases of depression than in mild cases.

SSRI Use and Frequently Asked Questions

Before taking any prescription medication as directed by your doctor, it is important to ask the prescribing doctor questions about the treatment and its pros and cons. Below are some of the frequently asked questions about SSRIs.

SSRIs Treat:
  • Major depressive disorder (MDD)
  • Generalized anxiety disorder (GAD)
  • Obsessive-compulsive disorder (OCD)
  • Panic disorder (PD)
  • Social Anxiety Disorder (SAD)
  • Social Phobia
  • Post-traumatic stress disorder (PTSD)
  • Bipolar disorder (when combined with other drugs)
  • Premenstrual dysphoric disorder (PMDD)

Who Is Prescribed SSRIs?

Doctors are more likely to prescribe SSRIs to women. One in four women in their 40s and 50s take antidepressants, and 13 percent of pregnant women take these drugs.

Why Do Doctors Prescribe SSRIs?

There are several reasons why doctors prescribe SSRIs. Some are for uses not approved by the U.S. Food and Drug Administration, known as off-label uses.

How Do SSRIs Work?

Nerve cells in our brain use various chemicals to pass on impulses. SSRIs work by increasing the levels of a brain chemical called serotonin, which plays a key role in mood. The body naturally produces serotonin and keeps it at a certain level, but SSRIs can increase that level by blocking (inhibiting) the re-absorption (reuptake) of serotonin.

Psychologist Alexander Bingham explains how antidepressants are supposed to work, in theory.

Who Should Take SSRIs?

SSRIs are usually the first choice for doctors treating depression or anxiety with prescription medications, but they’re not for everyone. It is normal to feel sad or “down” in the wake of stressful life events such as the death of a loved one, a job loss or a divorce. These feelings should ease or subside on their own. Patients may be candidates for antidepressants if they aren’t functioning well, if the symptoms last for several weeks without getting better, or if there is no apparent reason for the symptoms. This is especially true if patients have a history of depression.

Did You Know
Females are 2.5 times more likely to take antidepressants than males

Can Children Take SSRIs?

Many SSRIs are only FDA approved for use in adults but can be legally prescribed to treat depression or obsessive-compulsive disorder in children and adolescents. Prozac (fluoxetine) is the only FDA-approved medication for treating depression in children 8 and older, while Lexapro (escitalopram) is approved for children 12 to 17. Prozac, Zoloft (sertraline) and Luvox (fluvoxamine maleate) are approved for use in children and adolescents for the treatment of obsessive-compulsive disorder. Other SSRIs are not approved for use in children, but that does not mean a doctor can’t prescribe them as an off-label use for treating depression or anxiety disorders in patients under 18.

What Does The Treatment Involve?

SSRIs are usually taken daily. The goal is to ease or eliminate the symptoms within the first few weeks to months. Treatment duration depends on several factors, including the severity of the symptoms and how well each individual responds to treatments.

Most patients take SSRIs for several months, but some may require years of treatment. According to the CDC, 14 percent of Americans taking antidepressants have done so for 10 years or longer. The duration also depends on the chance of relapse. Patients with a history of depression or those going through a traumatic life event may experience a relapse of major depression. A relapse may also occur if a patient suddenly stops taking an SSRI (discontinuation) or if their dosage is significantly reduced.

How Effective Are SSRIs?

It’s difficult to pinpoint the effectiveness of SSRIs because each individual and case is unique. Our bodies respond to medications in different ways. Doctors may end up prescribing a number of different SSRIs and dosage options before a patient finds one that works. In general, the effectiveness is usually tied to the severity of the depression or anxiety disorder.

According to a 2017 study from the Institute for Quality and Efficiency in Health Care, about 40 to 60 out of 100 people who took an antidepressant noticed an improvement in their symptoms within six to eight weeks. Typically, someone with an anxiety disorder such as obsessive-compulsive disorder (OCD) or generalized anxiety disorder (GAD) may see improvements faster compared to patients with severe depression.

Did you Know?
Roughly 13.6% of whites take antidepressants — far more than blacks and Hispanics

How Much Do SSRIs Cost?

SSRIs can range from about $21 a month (sometimes less) for generic versions to several hundred dollars a month for certain brand name drugs, according to a study from Consumer Reports. Generic versions are available for all SSRIs on the market, including Prozac, Paxil, Zoloft and Lexapro.

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Understanding the Different Types of SSRIs

Although all SSRI drugs have the same mechanism of action — increasing serotonin levels in the brain — all SSRIs are not the same.

Each has slightly different pharmacological and pharmacokinetic characteristics, along with varying molecular structures. In other words, each drug has its own active ingredient with the same goal in mind.

These differences can be clinically significant, leading to variances in recommended dosage, common side effects, half-life (time required for the concentration of the drug in the body to decrease by half), effectiveness (including typical treatment duration) and potential drug interactions.

Prozac

FDA Approved
1987
Manufacturer
Eli Lilly
Common Uses Other Than Depression
Obsessive-Compulsive Disorder (OCD), Bulimia, Panic Disorder
Recommended Dosage
10 mg to 90 mg
Common Side Effects
Nausea, Diarrhea, Insomnia, Drowsiness, Dry mouth, Nervousness
FDA Approved for Children
Depression and OCD for ages 8 and older
Major Differences compared to other SSRIs
Only SSRI approved for children under 12

Zoloft

FDA Approved
1991
Manufacturer
Pfizer
Common Uses Other Than Depression
Obsessive-Compulsive Disorder, Premenstrual Dysphoric Disorder, Post-traumatic Stress Disorder, Panic Disorder, Social Anxiety
Recommended Dosage
25 mg to 200 mg
Common Side Effects
Nausea, Insomnia, Diarrhea, Sexual dysfunction (ejaculation failure and decreased libido)
FDA Approved for Children
Only for treating OCD
Major Differences compared to other SSRIs
One of the most prescribed antidepressants for pregnant women

Paxil

FDA Approved
1992
Manufacturer
GlaxoSmithKline
Common Uses Other Than Depression
Obsessive-Compulsive Disorder, Panic Disorder, Social Anxiety Disorder, Generalized Anxiety Disorder
Recommended Dosage
20 mg to 50 mg
Common Side Effects
Drowsiness, Nausea, Weight Gain, Insomnia, Dizziness
FDA Approved for Children
No
Major Differences compared to other SSRIs
Only SSRI to carry a Category D pregnancy warning, indicating human fetal risk based on clinical studies

Celexa

FDA Approved
1998
Manufacturer
Forest Pharmaceuticals
Common Uses Other Than Depression
Generalized Anxiety Disorder, Diabetic Neuropathy, Eating Disorders
Recommended Dosage
20 mg to 40 mg
Common Side Effects
Nausea, Vomiting, Increased sweating, Insomnia, Headaches, Drowsiness
FDA Approved for Children
No
Major Differences compared to other SSRIs
Increased risk of adverse heart conditions, including QT prolongation, a heart rhythm disorder

Lexapro

FDA Approved
2002
Manufacturer
Forest Pharmaceuticals
Common Uses Other Than Depression
Generalized anxiety disorder (adults)
Recommended Dosage
10 mg to 20 mg
Common Side Effects
Nausea, Insomnia, Headache, Diarrhea
FDA Approved for Children
Depression for ages 12 to 17
Major Differences compared to other SSRIs
Generally produces fewer or milder side effects for increased tolerability

Luvox

FDA Approved
2008
Manufacturer
Synthon Pharmaceuticals
Common Uses Other Than Depression
Obsessive-Compulsive Disorder, Panic Disorder, Posttraumatic Stress Disorder
Recommended Dosage
25 mg to 100 mg
Common Side Effects
Nausea, Insomnia, Drowsiness, Headache
FDA Approved for Children
Only for treating OCD
Major Differences compared to other SSRIs
Primarily used to treat OCD. It is not FDA approved to treat depression but is prescribed as an off-label use

SSRI Side Effects and Black Box Warnings

SSRIs have a number of common side effects, including fatigue, weight loss, apathy, insomnia, headaches, nausea and pupil dilation. They are also linked to sexual side effects such as repressed libido, erectile dysfunction (impotence) for men and difficulty achieving orgasm for men and women.

Side effects are more common with higher doses and are likely to improve or go away completely once the body adjusts to the medication. However, SSRI use can also lead to serious side effects, some of which are life-threatening.

Psychologist Alexander Bingham describes some of the worst side effects of SSRIs and explains how the drugs affect people differently.

Risk of Bleeding

Patients taking SSRIs have a reduced capacity for their blood to clot. A lower concentration of serotonin in platelets increases the risk for stomach or uterine bleeding, which means an increased need for a blood transfusion during or after surgery.

Hypnoatremia

This condition is a drop in a person’s sodium levels, which can lead to the accumulation of fluid in cells and is dangerous. Elderly people especially should be monitored for this condition from the beginning of treatment.

Withdrawal Symptoms

Another serious concern for SSRI patients is whether they will suffer withdrawal symptoms when they stop taking the antidepressants.

SSRIs technically are not considered addictive because they do not cause cravings in the body when the patient stops taking the drugs. However, studies show that the antidepressants can make users dependent on the drugs, and patients can suffer withdrawal symptoms.

Drug dependency is the state where a person needs steady or increasing doses of the drug to maintain normal functioning. Patients are warned not to stop taking SSRIs suddenly because they may experience withdrawal side effects.

Some Withdrawal Side Effects Include:
  • Nausea
  • Headaches
  • Problems with balance
  • Dizziness
  • Insomnia
  • Lethargy

Discontinuation Syndrome

In severe cases, patients will have a collection of symptoms called SSRI Discontinuation syndrome, which can last up to several weeks.

Common Symptoms of Discontinuation Syndrome Include:
  • Flu-like symptoms
  • Sensory and sleep disturbances
  • Problems with balance
  • Dysphoria (profound state of dissatisfaction)
  • Irritability and aggressiveness
  • Insomnia
  • Heightened anxiety

Suicide Black Box Warning

All SSRIs carry an FDA black box warning — the agency’s most stringent precaution — for an increased risk of suicidal thoughts and behaviors (suicidality) in adults and children 24 and younger.

Clinical Fact
Clinical studies found no significant correlation to an increased risk of suicidality in adults 25 and older and a reduced risk in adults 65 and older.

Only Prozac and Lexapro are FDA-approved for treating depression in children, while Prozac, Zoloft and Luvox are approved for treating children and adolescents with obsessive compulsive disorder. However, all SSRIs can be prescribed to children and teens as an off-label treatment for depression and anxiety disorders.

Timeline of SSRI Black Box Suicide Warning
  • 2004 - FDA Issues Public Warning For Children
    Warning : Antidepressants increase the risk of suicidal thinking and behavior (suicidality) in children and adolescents with major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of [Drug Name] or any other antidepressant in a child or adolescent must balance this risk with the clinical need. Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. [DRUG NAME] IS NOT APPROVED FOR USE IN PEDIATRIC PATIENTS EXCEPT FOR PATIENTS WITH [ANY APPROVED PEDIATRIC CLAIMS HERE].
  • 2006 - Warning Extended to Include Yound Adults as Old as 24
    Warning : Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of [Insert Drug Name] or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. SHORT-TERM STUDIES DID NOT SHOW AN INCREASE IN THE RISK OF SUICIDALITY WITH ANTIDEPRESSANTS COMPARED TO PLACEBO IN ADULTS BEYOND AGE 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. [Insert Drug Name] is not approved for use in pediatric patients.
  • 2004 - FDA Issues Public Warning for Children
    Warning : Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of [Insert Drug Name] or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. [Insert Drug Name] is not approved for use in pediatric patients.*MANUFACTURERS REQUIRED TO UPDATE WARNING TO INCLUDE INCREASED RISKS DURING INITIAL TREATMENT (1-2 MONTHS)

Unfortunately, this may have resulted in more suicide attempts among youth who needed antidepressants but did not take them because of the warning. A study found that antidepressant use in adolescents dropped 31 percent after the FDA issued the black box warning, but suicide attempts among youth increased 22 percent.

FDA's Involvement
The FDA revised the warning, recommending that physicians consider the risks of both prescribing and not prescribing the medication.

Parents and caregivers of children being treated for depression with SSRIs should watch for worsening irritability, nervousness, agitation, mood instability or sleeplessness.

Suicidal thoughts and behaviors are the most common symptoms of major depression for all ages. Doctors and their patients should carefully weigh the risks with the benefits when prescribing SSRIs to treat depression.

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SSRIs and Pregnancy

The FDA cautions women about the use of SSRI antidepressants during pregnancy.

Pregnant Woman Taking Medication
Paxil carries the Category D Warning showing positive evidence of human fetal risk.

One way the agency has conveyed this warning is with letter grades, or categories, that are assigned to prescription medications to denote their safety ratings. Most SSRIs are Category C, meaning they have been known to harm laboratory animals when they ingested the drugs in large quantities.

Paxil is the one exception. The drug and its generic form (paroxetine) carry a Category D warning, which means that there is “positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans.”

Zoloft and Prozac are the two most common SSRIs prescribed to pregnant women, but Paxil or any other SSRI can be prescribed if doctors think the benefits of the medication outweigh the potential risks. Untreated depression in pregnant women can also lead to serious complications, including continued depression after delivery (postpartum depression) and even the potential of pregnancy termination or suicide.

Mothers Taking Paxil
Mothers who take Paxil or Prozac during the early stages of pregnancy are 2 to 3.5 times more likely to give birth to a child with a congenital disorder, according to a 2015 study published in the British Medical Journal.

Common Birth Defects

There has been a series of conflicting studies in recent years regarding the association of SSRI drugs and birth defects. A comprehensive study from the National Center on Birth Defects and Developmental Disabilities revealed that the most common reported links include heart, brain and abdominal birth defects.

Common Birth Defects from SSRI Include:
Heart Defects
The most common heart conditions in babies are septal defects — atrial septal defects (ASD) and ventricular septal defects (VSD) — which are holes in the heart that compromise blood flow.
Persistent Pulmonary Hypertension of the Newborn (PPHN)
This condition, which damages the heart and lungs, occurs in utero but is rarely detected until the baby is born. In 2006, the FDA released a safety announcement warning consumers of the risk of PPHN when SSRIs are taken during the last half of pregnancy.
Anencephaly
This is a devastating birth defect that leaves a baby without a large part of the functioning brain, skull and scalp and is always fatal. Mothers who took Paxil during pregnancy have given birth to babies with this condition. Craniosynostosis, where one or more fibrous joints in an infant’s skull fuse together, has been linked to Prozac.
Cleft Lip and Palate
Clefts are gaps left when facial structures are forming and typically occur on the top lip and roof of the mouth. These deformities usually require multiple surgeries to correct and can hamper feeding, breathing and speech development.
Respiratory Distress
Respiratory Distress Syndrome is a type of breathing difficulty that occurs in premature babies and is attributed to the baby's underdeveloped lungs. Respiratory distress also is a symptom of Neonatal Adaptation Syndrome, which researchers have linked to the use of SSRIs in the third trimester.

Some researchers suggest that it is too difficult to quantify the risk of SSRIs during pregnancy because untreated depression and anxiety disorders can also lead to birth defects and an increased risk of a child developing autism.

Timeline of SSRI Lawsuits, Settlements & Verdicts

Drug manufacturers have paid billions in government fines, class-action settlements and lawsuit verdicts over potential dangers of SSRI medications. Some notable ones include:

  • 1994
    A jury in Indiana ruled in favor of drugmaker Eli Lily over allegations that Prozac was to blame for Joseph T. Wesbecker’s 1989 rampage where he shot and killed eight colleagues before taking his own life. It was the first major SSRI suicide case to go to trial.
  • 2000
    Eli Lilly reportedly paid more than $50 million to settle Prozac lawsuits related to suicides or murders.
  • 2002
    Hundreds of residents of Florida received unsolicited samples of Prozac in the mail from Eli Lilly and Walgreens. A class action lawsuit was filed against Eli Lilly, but the case was eventually dismissed.
  • 2006
    A multidistrict litigation consolidated in the Central District of California related to Paxil withdrawal symptoms settled for $78.7 million. Ultimately, drugmaker GlaxoSmithKline (GSK) would settle 3,200 claims related to Paxil withdrawal for $160 million.
  • 2009
    A Pennsylvania jury awarded $2.5 million to the Kilker family after Lyam Kilker was born with heart defects attributed to his mother’s use of Paxil while pregnant. The jury found that GSK failed to warn users of the drug’s risks.
  • 2010
    A federal investigation of Forest Pharmaceuticals Inc., a subsidiary of Forest Laboratories, lead to a $313 million settlement to resolve criminal and civil complaints. Claims included that Forest illegally marketed Celexa and Lexapro to children and adolescents and paid doctors to prescribe the drugs.
  • 2010
    GSK settled more than 800 cases involving Paxil birth defects for $1.14 billion, averaging more than $1.2 million per case.
  • 2014
    Forest Laboratories paid $10.4 million to settle a class-action lawsuit related to illegal promotion of Lexapro and Celexa to children.
  • 2016
    U.S. District Court for the Eastern District of Pennsylvania Judge Cynthia M. Rufe dismissed more than 300 lawsuits from the MDL related to Zoloft birth defects.
  • 2017
    GSK agreed to pay $6.2 million to settle a class action lawsuit involving 50 Canadian mothers and their children over links between Paxil and birth defects.
  • 2017
    An Illinois federal jury found GSK liable for the death of former corporate lawyer Steward Dolin, who was taking a generic version of Paxil before committing suicide in 2010. Dolin’s widow, Wendy, was awarded $3 million in damages following five weeks of trial testimony.
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Alternatives to Taking SSRIs

SSRIs are considered second-generation antidepressants and are often prescribed to treat depression before other types of antidepressants, including serotonin and norepinephrine reuptake inhibitors (SNRIs) and tricyclic antidepressants (TCAs).

Did You Know
A 2014 study found that patients who were given antidepressants but were not truly clinically depressed had a higher risk of suicidal thoughts or behaviors while using the medications.

SSRIs can improve the symptoms of depression, but they can also cause serious side effects. A 2014 study from researchers at the Nordic Cochrane Centre and the University of Copenhagen found that patients who were given antidepressants but were not truly clinically depressed had a higher risk of suicidal thoughts or behaviors while using the medications.

The Danish researchers suggest that many of the prescriptions were given “unnecessarily” as an alternative to other treatment options, including therapy. SSRIs should only be taken if the patient and their doctor or mental health professional believe it is the best possible option for treating severe depression or a serious anxiety disorder.

SNRIs and TCAs as Alternatives to SSRIs

Serotonin and norepinephrine reuptake inhibitors (SNRIs) work similarly to SSRIs, but instead of increasing only serotonin levels, SNRIs also increase the amount of norepinephrine in the brain.

Fact
An additional 60% of Americans take antidepressants for two years or longer

By increasing norepinephrine levels, brain cells seem to communicate better, which can boost a person’s mood.

However, SNRIs may decrease libido, cause weight gain and increase fatigue and drowsiness. More serious side effects include birth defects in pregnant women and a risk of withdrawal from discontinuation.

Tricyclic antidepressants (TCAs) are an older class of antidepressants, having been available for more than 50 years. They can be as effective as newer antidepressants, but they usually carry more side effects, including dizziness, constipation and dry mouth. TCAs might be prescribed if other antidepressants are proven ineffective.

Examples of TCAs Include:
  • Amitriptyline
  • Clomipramine (Anafranil)
  • Imipramine (Tofranil)
  • Doxepin (Silenor, Zonalon, Prudoxin)
  • Trimipramine (Surmontil)

Alternatives to Medication for Treating Depression

The most common alternative is therapy, which helps a person cope with feelings of hopelessness or anxiety. Cognitive behavioral therapy is a type of psychotherapy in which negative patterns of thought are challenged in order to change unwanted behavior patterns.

A 2012 study published in The Lancet discovered that nearly half of patients who had depression and were resistant to antidepressant medications benefited from cognitive behavioral therapy. Therapy can also be an effective option for women with depression who don’t want to risk taking antidepressant drugs while pregnant.

Psychologist Alexander Bingham discusses nonpharmaceutical treatments for depression.
Other Alternatives to Medication Include:
Eating Healthy
Some studies show that a diet rich in “superfoods” such as tomatoes (contains antioxidants, including lycopene), seafood (salmon and tuna contain omega-3 fatty acids) and spinach and avocados (contain folic acid) can naturally ease symptoms of depression.
Exercising Regularly
Working out temporarily boosts feel-good chemicals called endorphins. Regular exercise can “rewire” the brain to think more positively.
Getting Plenty of Sleep
Sleep affects our mood, especially those suffering from severe depression. Unfortunately, depression can make getting sleep more difficult, but things like avoiding distractions in the bedroom — TV, computer, phone, etc. — along with eating healthy and exercising regularly can improve sleep patterns.
Taking Natural Supplements
Natural supplements such as fish oil and folic acid have been shown to reduce symptoms of depression in some patients and may be a useful alternative for patients who choose not to take prescription antidepressants. Always consult with a doctor before beginning any supplement regimen.
Trying New Hobbies
Sometimes something as simple as taking up a new hobby or doing an enjoyable activity can improve depression. Breaking a normal routine can add some variety to a patient’s life. This could include taking a trip, spending more time with loved ones or taking part in an activity like team sports or yoga to ease the mind and relieve stress.

These options may not completely eliminate a person’s depression, but could relieve symptoms, lessening the need for SSRIs or other prescription antidepressants. A doctor or mental health professional can help navigate the process and decide which option or options might be right for each individual.

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Please seek the advice of a medical professional before making health care decisions.