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Antidepressants & SSRIs

Selective serotonin reuptake inhibitors (SSRIs) are antidepressants that work by altering the levels of a mood-enhancing chemical called serotonin. But when pregnant women take them they increase the risk of autism spectrum disorder and birth defects in newborns.

Females are

2.5X

More likely to take antidepressants than males

Roughly

13.6%

of whites take antidepressants, far more than Blacks and Hispanics

An Additional

60%

of Americans take antidepressants for two years or longer

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. 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.

Prozac 20mg Tablets

Common Drugs

Prozac, Zoloft, Paxil, Celexa, Lexapro

Paxil Pills

Main Active Ingredients

Depends on specific SSRI

Zoloft 100mg Tablets

Common Active Ingredients

Fluoxetine, Sertraline and Paroxetine

Luvox Tablets

Black Box Warning

Increased risk of suicidal thoughts and behaviors

Lexapro 10mg Pills

First FDA Approved SSRI

Prozac (1997)

Celexa 10mg Pills

Used to Treat

Major depression disorder and general anxiety disorder

SSRI USE
And Frequently Asked Questions

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.

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

Young Woman Crouched on Floor with Head Down

Anxiety disorders treated by SSRIs include:

  • Generalized anxiety disorder (GAD)
  • Obsessive-compulsive disorder
  • Panic disorder
  • Social Phobia
  • Post-traumatic stress disorder (PTSD)
  • Bipolar disorder (when combined with other drugs)

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.

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. A person may be a candidate 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 you have a history of depression.

Can Children Take SSRIs?

Many SSRIs are only FDA approved for use in adults only, but some can treat depression 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 treatments. 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.

What Is The Effectiveness of SSRIs?

It’s difficult to pinpoint the effectiveness of SSRIs since 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.

How Much Do These Drugs 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.

Understanding
The Different Types of SSRIs

While 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.

FDA Approved
1987 1991 1992 1998 2002 2008
Manufacturer
Ely Lilly Pfizer GlaxoSmithKline Forest Pharmaceuticals Forest Pharmaceuticals Synthon Pharmaceuticals
Common Useses Other Than Depression
Obsessive-Compulsive Disorder (OCD), Bulimia, Panic Disorder Obsessive-Compulsive Disorder, Premenstrual Dysphoric Disorder, Posttraumatic Stress Syndrome, Panic Disorder, Social Anxiety Obsessive-Compulsive Disorder, Panic Disorder, Social Anxiety Disorder, Generalized Anxiety Disorder Generalized Anxiety Disorder, Diabetic Neuropathy, Eating Disorders Generalized anxiety disorder (adults) Obsessive-Compulsive Disorder, Panic Disorder, Posttraumatic Stress Disorder
Recommended Dosage
10 mg to 90 mg 25 mg to 200 mg 20 mg to 50 mg 20 mg to 40 mg 10 mg to 20 mg 25 mg to 100 mg
Common Side Effects
Nausea, Diarrhea, Insomnia, Drowsiness, Dry mouth, Nervousness Nausea, Insomnia, Diarrhea, Sexual dysfunction (ejaculation failure and decreased libido) Drowsiness, Nausea, Weight Gain, Insomnia, Dizziness Nausea, Vomiting, Increased sweating, Insomnia, Headaches, Drowsiness Nausea, Insomnia, Headache, Diarrhea Nausea, Insomnia, Drowsiness, Headache
FDA Approved for Children
Depression and OCD for ages 8 and older Only for treating OCD No No Depression for ages 12 to 17 Only for treating OCD
Major Differences compared to other SSRIs
Only SSRI approved for children under 12 One of the most prescribed antidepressants for pregnant women Only SSRI to carry a Category D pregnancy warning, noting human fetal risk based on clinical studies Increased risk of adverse heart conditions, including QT prolongation, a heart rhythm disorder Generally produces fewer or milder side effects for increased tolerability Primarily used to treat OCD. It is not FDA approved to treat depression but is prescribed as an off-label use

Serious 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 difficult 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.

Other Rare and Severe Side Effects of SSRIs

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.

If you or a loved one have experienced complications from the popular SSRI Zoloft you may be eligible for compensation.

Get a Free Case Review

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 the antidepressants can make users dependent on them, and they can suffer withdrawal symptoms.

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

Restless Man on Edge of Bed

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 Warning

All SSRIs carry a 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 young adults as old as 24

Warning

Antidepressants increased the risk compared to placebo of suicidal thinking and behaior (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 Established 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. Familes 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 established 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 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.

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 they convey this warning is with the letter grades, or categories, that are assigned to prescription medications to denote their safety ratings. Most SSRIs are grade 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 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 SSRIs can be prescribed if doctors feel 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 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 the most common reported links include heart, brain and abdominal birth defects.

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 hearts 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 a baby 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

Cleft lip and palate

Clefts are the gaps left when the 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 SSRIs
Lawsuits and Litigations

Symptoms of Type 2 are similar in most people, according to the American Diabetes Association. But some might have fewer or milder warning signs that make the disease more difficult to detect. Early detection and proper management of diabetes may help decrease the risk of complications.

  • 1994

    A jury in Indiana ruled in favor of drugmaker Ely 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

    Ely Lilly had 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 Ely 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 GSK failed to warn users of the drug’s risks.

  • 2010

    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.

  • 2010

    GSK settled more than 800 cases involving Paxil birth defects for $1.14 billion, averaging more than $1.2 million per case.

  • 2012

    GSK agreed to plead guilty to misbranding Paxil and Wellbutrin (another antidepressant) for unapproved uses, including illegal marketing to children. The fraud case ultimately settled for $3 billion and is still the largest settlement by a pharmaceutical company in U.S. history.

  • 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.

SSRI Lawsuits

Alternatives
To Taking SSRIs

SSRIs are considered second-generation antidepressants and are often prescribed to treat depression before other types of antidepressants — because of better tolerability — including serotonin and noradrenaline reuptake inhibitors (SNRIs) and tricyclic antidepressants (TCAs).

DID YOU KNOW

A 2014 study found that antidepressants given to patients not clinically depressed had a higher risk of suicidal thoughts or behaviors while medicated.

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 antidepressants given to patients who were not truly clinically depressed had a higher risk of experiencing suicidal thoughts or behaviors while using the medications.

The Danish researchers suggest 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 believes it is the best possible option for treating severe depression or a serious anxiety disorder.

SNRIs and TCAs as Alternatives to SSRIs

Serotonin and noradrenaline reuptake inhibitors (SNRIs) work similarly to SSRIs, but instead of increasing only serotonin levels, SNRIs also increase the amount of noradrenaline, a hormone that produces a wide range of effects on the body.

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

Birth Defects Caused By SSRIs

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

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.

Pink and Orange Pills

Common Types of Natural Antidepressants:

  • Amitriptyline
  • Clomipramine (Anafranil)
  • Imipramine (Tofranil)
  • Doxepin (Silenor, Zonalon, Prudoxin)
  • Trimipramine (Surmontil)

Types of ‘Natural Antidepressants’

There are alternatives to medications 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 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.

OTHER SO-CALLED “NATURAL ANTIDEPRESSANT” OPTIONS 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 positive.

  • 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.

Drugwatch.com Author

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    1. U.S. Food and Drug Administration. (2007, May 2) FDA Drug Safety Communication: Antidepressant Use in Children, Adolescents, and Adults. [Safety announcement]. Retrieved from http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm096273.htm
    2. U.S. Food and Drug Administration. (2011, December 14) FDA Drug Safety Communication: Selective serotonin reuptake inhibitor (SSRI) antidepressant use during pregnancy and reports of a rare heart and lung condition in newborn babies. [Safety announcement]. Retrieved from http://www.fda.gov/Drugs/DrugSafety/ucm283375.htm
    3. National Institute of Mental Health. Antidepressant Medications for Children and Adolescents: Information for Parents and Caregivers. National Institute of Mental Health. Retrieved from http://www.nimh.nih.gov/health/topics/child-and-adolescent-mental-health/antidepressant-medications-for-children-and-adolescents-information-for-parents-and-caregivers.shtml
    4. U.S. Food and Drug Administration. (2006, July 19) FDA Public Health Advisory: Treatment Challenges of Depression in Pregnancy and the Possibility of Persistent Pulmonary Hypertension in Newborns. [Public Health Advisory] Retrieved from http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/PublicHealthAdvisories/ucm124348.htm
    5. Alwan, S., Reefhuis, J., Rasmussen, S., Olney, R., and Friedman, J. (2007, June 28) Use of Selective Serotonin-Reuptake Inhibitors in Pregnancy and the Risk of Birth Defects. The New England Journal of Medicine. Retrieved from http://www.nejm.org/doi/full/10.1056/NEJMoa066584
    6. Friedman, Richard A. and Leon, Andrew C. (2007, June 7) Expanding the Black Box — Depression, Antidepressants, and the Risk of Suicide. The New England Journal of Medicine. Retrieved from http://www.nejm.org/doi/full/10.1056/NEJMp078015