What are SSRIs and Why are They Used?

Selective serotonin reuptake inhibitors (SSRIs) are a class of medicines used to treat many different mental health conditions. Most commonly, SSRIs are prescribed to treat depression [1], but they are also used to treat other conditions, including anxiety, obsessive-compulsive disorder (OCD), and panic disorder. SSRIs are the most widely used type of antidepressants. Compared to older antidepressant medicines, SSRIs have fewer side effects, and patients usually tolerate SSRIs very well, which is why doctors prescribe them more often than any other type of antidepressant [1].

Serotonin is a chemical messenger in the brain that helps send messages between brain cells called neurons. Neurons act like electrical wires, carrying and sending electrical and chemical signals throughout the brain and nervous system. Serotonin plays a role in managing sleep, digestion, and bone health, but one of its most important roles is in mood regulation. Serotonin is known as the body’s “feel-good” chemical. People tend to feel happier, calmer, more motivated, and stable when serotonin is present at normal levels. People who live with depression tend to have low amounts of serotonin, which means their moods cannot be regulated as well. Low serotonin can lead to symptoms like social withdrawal, sadness, low self-esteem, and depression.

But how does serotonin do these things? In the brain, a neuron (let us call it neuron 1) sends serotonin to a second neuron (which we will call neuron 2). Serotonin is sent through a synapse, which is the space between two neurons that allows a chemical signal to pass between them. The serotonin that is not used by neuron 2 is usually taken up back into neuron 1, with the help of a serotonin channel in the cell membrane, patiently sitting on neuron 1 waiting to do its job.

SSRIs allow more serotonin to be present in the brain by preventing serotonin from being taken back up into neuron 1 (Figure 1). Essentially, these drugs stop the channel from doing its job, which causes more serotonin to be present in the synapse between neuron 1 and neuron 2. This increased serotonin is very helpful for those who deal with depression caused by low levels of serotonin in the brain.

Activation Syndrome in Young People Taking SSRIs

Researchers have studied how SSRIs affect the brain for several decades (Figure 2). However, more research is needed to understand how this medicine can affect children and adolescents. Specifically, physicians and researchers have identified some extreme side effects that children and adolescents can experience from taking certain antidepressants and other medications to treat mental health conditions. They call these rare side effects activation syndrome.

What is activation syndrome? Imagine you take an antidepressant medication prescribed by your doctor so that you can feel less depressed and anxious and more motivated and content. However, after taking this medication, you start to feel worse than you did before. Maybe you feel irritable, restless, hyperactive, or impulsive [2, 3]. In extreme cases, children and teenagers can experience increased thoughts about and risk of suicide. Because the list of symptoms kids with activation syndrome can experience is very long, doctors still struggle to define and identify this dangerous side effect. It is also difficult for doctors to diagnose because the range and intensity of symptoms can vary between individuals. Additionally, sometimes the symptoms of activation syndrome are difficult to tell apart from the symptoms of the child’s original mental health condition [2–4]. Unfortunately, treating activation syndrome is not as easy as stopping the medication. If someone abruptly stops taking SSRIs, they can experience dangerous withdrawal symptoms that are physical (dizziness, headache, muscle aches, nausea, etc.), chemical (“brain zaps”, tingling, burning), or emotional (anxiety, agitation, mood swings, etc.). Doctors have to carefully adjust the dose or slowly reduce the medication while monitoring children and adolescents.

There are several theories that could explain why children and adolescents might experience extreme, rare side effects from SSRIs. One common theory suggests that these young individuals could have more serotonin activity than normal in a part of the brain called the frontal cortex [2]. For example, in some kids who are around the age of puberty, the neurons in this brain region might release more serotonin than usual [2, 3]. When these kids take SSRIs, and the channels that allow neurons to take back extra serotonin are blocked, the high levels of serotonin floating around in the synapses may “overstimulate” neuron 2, leading to the symptoms of activation syndrome (Figure 2). Although this theory is still unproven and the cause of activation syndrome remains a mystery, blocking the effects of serotonin on neurons seemed to improve the extreme side effects [4].

Why is Activation Syndrome Less Concerning in Adults?

Compared to children and teenagers, adult brains are fully developed. Certain areas in the brains of children and teenagers, important for learning and behavior, are still growing. For example, the frontal lobe is critical for planning, decision making, and movement; and the hippocampus and amygdala are essential for memory and emotional processing. These brain areas can be negatively impacted by factors inside and outside the body, including medications or lifestyle activities like school, work, social groups, and social media [5]. While researchers still do not know for sure, children and teenagers may be more likely to experience problems from medication because these brain areas are still developing [4]. When three critical brain regions are not working properly as they should be, this can cause a child or teenager to experience a wide range of side effects (Figure 3).

Questions about how and why SSRIs result in dangerous side effects like activation syndrome can be investigated by studying a young individual’s medical history, prior risk factors from family or social history, or environmental cues. For example, changes in hormones or exposure to smoking and unhealthy environments can make a growing child more vulnerable to experiencing side effects. Some children and adolescents do not respond to SSRI medications because of these factors [2, 4]. Children under the age of 13 are more sensitive than older children are to changes in the brain following an extreme side effect. Children can be more susceptible to mental health conditions based on how old they were at the time an adverse event occurred. Age is a key factor used by physicians to figure out how early a problem starts and potentially why. In addition, just getting older and more mature often helps reduce extreme side effects and causes these problems to go away on their own.

To safely prescribe SSRI medicines to children and adolescents, doctors must consider many factors. First, they must make sure the diagnosis of the mental health condition is correct. Different conditions need different medicines to treat them. Effective medication management requires doctors to tailor treatment based on a child’s age, the specific drug, drug duration, timing of the dose, and specific factors that match the individual’s symptoms [4]. By prioritizing these factors, healthcare providers ensure patient-centered care for children, adolescents, and adults receiving SSRIs or other psychiatric medications. Fully understanding a patient’s mental and physical health can help doctors make sure they are prescribing the right medication in the right amount—and will also help them understand when they need to stop a particular medication and how to do so.

Glossary

Selective Serotonin Reuptake Inhibitors (SSRIs): ↑ A class of antidepressant medicines that increase serotonin levels in the brain by preventing serotonin from being taken back into neurons.

Mental Health Conditions: ↑ Conditions involving changes in emotion, thinking, or behavior (or combination of these).

Antidepressant: ↑ A type of medicine used to treat depression and several other mental health conditions.

Side Effect: ↑ A secondary or undesirable effect of a drug or medical treatment.

Serotonin: ↑ A chemical messenger in the brain that helps regulate mood, sleep, and other body functions.

Neurons: ↑ Cells that make up the brain and nervous system.

Synapse: ↑ Space between neurons that serves as a relay station for communication between the two cells.

Activation Syndrome: ↑ A group of symptoms, such as restlessness or hyperactivity, that can sometimes occur after starting certain antidepressant medications.

Conflict of Interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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