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How Do SSRIs Work in the Teen Brain?

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SSRI is an acronym that parents and teens may hear when researching options for treating depression. SSRI stands for selective serotonin reuptake inhibitor. This drug is the most commonly prescribed antidepressant. In addition, SSRIs are prescribed to treat anxiety. How do SSRIs work? Let’s take a closer look.

First, a few statistics: The number of people using antidepressant prescription has dramatically grown over the past two decades. In fact, antidepressant use increased by 64 percent in the United States between 1999 and 2014, according to the American Psychological Association. Furthermore, 7.8 percent of young adults ages 20 to 39 take antidepressants, and 3.4 percent of adolescents ages 12 to 19 take these drugs.

How Do SSRIs Work?

SSRIs work by affecting brain chemicals called neurotransmitters. These neurotransmitters send messages between brain cells, also called neurons. Their messages help regulate emotion and therefore directly impact mental health.

To understand the process better, let’s break down the acronym.

Selective: The word “selective” indicates that SSRIs primarily increase levels of the neurotransmitter known as serotonin. Serotonin is only one of the many neurotransmitters in the brain. Dopamine and norepinephrine are two of the other brain chemicals. 

Serotonin: People with depression often have low levels of serotonin in areas that regulate mood. SSRIs increase levels of serotonin in the brain, with the goal of helping these areas to function better.

Reuptake: When neurons send signals to one another, they release small amounts of serotonin or another neurotransmitter. Subsequently, they take back the neurotransmitter they released in order to use it to send another signal. This process is called “reuptake.” 

Inhibitor: SSRIs for anxiety and depression block the reuptake of serotonin in the brain. Therefore, more serotonin is available to regulate mood.

Antidepressants and the Teenage Brain

How do SSRIs work? When it comes to antidepressants and the teenage brain, we are talking about dramatic cerebral changes. These changes can take place very quickly after a teen begins using an SSRI. In fact, researchers have observed changes in the functional structure of the brain after a single dose of SSRI medication.

This is especially significant for adolescents, because the teenage brain is still immature. In particular, the prefrontal cortex, which controls reasoning and self-regulation, is not fully developed. Hence, introducing pharmaceuticals during this growth process can hinder healthy brain maturation. Research on how SSRIs work indicates that the teen brain is especially vulnerable to disruption by SSRIs and other antidepressant medications.

FDA-Approved SSRIs for Depression

The Food and Drug Administration (FDA) has approved a number of SSRIs to treat depression. They include the following:

  • Fluoxetine (Prozac)
  • Sertraline (Zoloft)
  • Citalopram (Celexa)
  • Escitalopram (Lexapro)
  • Paroxetine (Paxil, Pexeva)
  • Vilazodone (Viibryd).
  • Fluvoxamine (also used to treat Obsessive-Compulsive Disorder).

In addition to SSRIs, antidepressant categories include SNRIs, which block the reuptake of serotonin and norepinephrine, and NDRIs, which block the reuptake of norepinephrine and dopamine.

SSRI Side Effects

Asking the question, “How do SSRIs work?” is only half the battle. Understanding the side effects vary for physical, emotional and mental is important, and can include:

  • Drowsiness
  • Nausea
  • Dry mouth
  • Insomnia
  • Diarrhea
  • Nervousness, agitation, or restlessness
  • Dizziness
  • Headache
  • Blurred vision
  • Rash
  • Pain in the joints or muscles
  • Reduced libido.

Furthermore, a serious SSRI side effect is reduced blood-clotting capacity. Hence, those taking SSRIs have a higher risk for internal bleeding. This risk increases when the person is also taking aspirin or ibuprofen. Moreover, some antidepressants can cause dangerous reactions when combined with herbal supplements or with other prescription or over-the-counter medications.

Serotonin Syndrome

In rare cases, SSRIs can cause high levels of serotonin to accumulate in the body. Most often, this occurs when an individual is taking two serotonin-increasing medications—such as an SSRI and certain drugs for headaches or pain. Moreover, the herbal supplement St. John’s Wort also increases serotonin in the brain and thus should not be combined with SSRIs.

Symptoms of serotonin syndrome include the following:

  • Anxiety
  • Agitation and restlessness
  • Sweating
  • Confusion
  • Shaking
  • Lack of coordination
  • Increased heart rate.

Those taking SSRIs who experience any of these signs should seek immediate medical attention.

SSRIs and Suicidal Ideation in Teens

Parents whose children are suffering from depression often ask doctors for advice about the safest antidepressant for teenagers. However, research shows that antidepressants may actually increase suicidal thoughts and behaviors in children, teenagers, and young adults under 25. The highest risk is in the first few weeks after an adolescent begins taking the drug, or after the dosage is changed.

A review study looked at the question, how do SSRIs work? Researchers examined 24 studies involving 4,400 teens and young adults. The review compared the rate of suicidal thoughts among participants taking an antidepressant and participants who were given a placebo. Researchers found that the likelihood of having suicidal thoughts doubled for those taking antidepressants, including SSRIs—from 2 percent to 4 percent. (No participants in the study committed suicide.)

As a result, in 2004, the FDA began requiring that all antidepressants include a “black box warning” on package inserts for the drug. Short of withdrawing a drug from the market, a black box warning is the FDA’s strongest available measure. The warning for antidepressants mentions the increased risk of teen suicidal ideation. In addition, it mentions the potential for increased hostility and agitation in children, adolescents, and young adults.

What to Watch for When a Teen Is On SSRIs

During the first few months when a teen or young adult is on an SSRI, parents should be particularly vigilant about watching for signs of an increased suicide risk:

  • Talking about suicide or expressing suicidal thoughts
  • Increased depression symptoms
  • Agitation or restlessness
  • Panic attacks and other symptoms of anxiety
  • Insomnia
  • Irritability and aggression
  • Impulsive behavior
  • Manic behavior
  • Any unusual change in behavior.

If a teen has suicidal thoughts when taking an antidepressant (or at any time), they need to receive immediate attention at a doctor’s or clinician’s office or in an emergency room.

Do SSRIs Work?

The question is not only how do SSRIs work, but also, do SSRIs work? A 2016 meta-analysis of data from 34 trials involving 5,260 patients revealed that the vast majority of these drugs are ineffective for adolescents and may be dangerous.

The study found that only fluoxetine (Prozac) was more effective than a placebo in relieving symptoms of major depression in teens and young adults. “Antidepressants in the acute treatment of major depressive disorder do not seem to offer a clear advantage for children and adolescents,” stated lead researchers Andrea Cipriani of the University of Oxford and Xinyu Zhou of China’s Chongqing Medical University.

“Antidepressants, possibly including fluoxetine, are likely to be more dangerous and less effective treatments than has been previously recognized, so there is little reason to think that any antidepressant is better than nothing for young people.”

—Jon Jureidini, University of Adelaide, Australia, regarding the 2016 study

Going Off SSRI Medication

Medication is not the only approach for addressing teen depression. In fact, studies show that clinical and holistic methods for decreasing teen anxiety and depression can be equally or more effective than prescription medication.

However, because SSRIs impact the brain, it can be dangerous to stop taking them suddenly. Going off the drug all at once can lead to a condition called “discontinuation syndrome.” The syndrome causes withdrawal-like symptoms, including nausea, dizziness, uneasiness, fatigue, and lethargy.

Therefore, teens and young adults should get advice from a qualified clinical professional on how to safely discontinue the medication.

Alternatives to Antidepressants

In general, antidepressant medications, if used at all, should be one part of a comprehensive treatment approach that includes clinical therapy, monitoring of suicide risk, and education for parents and children. There are many effective non-pharmaceutical approaches to treating depression in adolescents.

Therapeutic modalities: Cognitive Behavioral Therapy, Dialectical Behavioral Therapy, and experiential therapies, such as Adventure Therapy and Equine-Assisted Therapy, are powerful and effective methods for treating depression in adolescents.

Physical activity: Exercising three times a week for 30 minutes can be as effective as medication in reducing depression, according to one study. Moreover, physical activity outside also offers the mental health benefits of time in nature.

The meal as medicine: In a groundbreaking study known as the SMILES Trial, one-third of participants experienced none of their depressive symptoms after three months of eating a healthy diet.

Meditation and yoga: Mindfulness-based practices may be just as impactful as SSRIs and other drugs in treating teen depression and anxiety, according to a review study at Johns Hopkins.

Read “Teens and Antidepressants: The Case for Holistic Treatment.”

In summary, when researching the question “How do SSRIs work?,” reviewing the scientific evidence gives a more complete picture of these commonly used antidepressants. Doctors and parents should understand the potential ssri side effects and possible disruption of brain development when considering SSRIs for teens. Most important, there are many effective, non-pharmaceutical approaches to addressing teen depression.


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