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Exploring Antidepressants: Selective Serotonin Reuptake Inhibitors (SSRIs)

Selective serotonin reuptake inhibitors are the most commonly prescribed medications for treating major depressive disorder, anxiety disorders, and other psychological conditions.

By
  • Alivia Kaylor, MSc
Published: 27 Apr 2022

Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressant drugs that treat depression and other mental health conditions by inhibiting the reabsorption of serotonin by neurons in the brain.

According to the National Alliance on Mental Illness (NAMI), nearly 1 in 5 adults and 1 in 6 adolescents (ages 6–17 years) experience mental illnesses such as depression and anxiety each year in the United States.

Like anxiety, depression is linked to low levels of serotonin, dopamine, and norepinephrine, making SSRIs effective for treating these kinds of mental illnesses.

Because a person's brain chemistry may contribute to their psychological condition, antidepressants can alter the brain’s chemistry and alleviate burdensome symptoms.

What Are SSRIs?

SSRIs serve as first-line care in treating depression and anxiety disorders by increasing serotonin — a chemical messenger that carries signals between brain nerves and influences mood, emotion, and sleep.

SSRIs function by blocking the reabsorption or reuptake of serotonin into the brain nerves (neurons), increasing the available serotonin to improve the transmission of messages between neurons.

Citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, Symbyax), fluvoxamine (Luvox, Luvox CR), paroxetine (Paxil, Paxil CR, Pexeva), sertraline (Zoloft), and vilazodone (Viibyrd) are the common SSRIs prescribed to treat depression, anxiety, and mental health disorders.

SSRIs also treat pain and other conditions, including premenstrual syndrome (PMS), fibromyalgia, and irritable bowel syndrome (IBS). Additionally, SSRIs are effective in treating obsessive­­­–compulsive and panic disorders, social phobias, and eating disorders.

SSRIs are the most commonly prescribed antidepressant because they are relatively safe, can ease moderate-to-severe depression symptoms, and typically cause fewer side effects than other antidepressants. SSRIs have better overall safety and tolerability than older antidepressants.

Key findings from the 2005–2008 National Health and Nutrition Examination Surveys show that 11% of Americans aged 12 years and older take antidepressants, equating to nearly 25 million people.

Benefits and Risks of SSRIs

SSRIs have minimal effects on other neurotransmitters in the brain like dopamine and norepinephrine and, therefore, have fewer reported side effects than tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). However, possible side effects of SSRIs include the following:

  • Nausea or vomiting
  • Constipation or diarrhea
  • Dry mouth
  • Impact on appetite, weight loss or weight gain
  • Nervousness, agitation, or restlessness
  • Dizziness
  • Excessive sweating
  • Blurred vision
  • Headaches
  • Insomnia or drowsiness
  • Sexual problems, such as reduced libido, difficulty reaching orgasm, or inability to maintain an erection (erectile dysfunction)

Daniel Carlat, MD, associate clinical professor of psychiatry at Tufts University School of Medicine, told Healthline that “selective serotonin reuptake inhibitors are very safe drugs, generally speaking.”

“While there are some pretty minor side effects, it would be very hard for people to do any damage to themselves by taking an SSRI,” he continued.

SSRIs may increase the risk of fetal developmental issues. For instance, studies show that paroxetine (Paxil) has been linked to fetal heart conditions in newborns.

Some SSRIs can interact with other drugs, causing lowered effectiveness and life-threatening reactions. For example, fluoxetine has a considerably longer half-life than other SSRIs. Therefore, side effects and drug interactions might occur for an extended period of time following discontinuation of treatment.

SSRIs may increase the risk of bleeding when taking other medications that increase the risk of bleeding, such as aspirin, warfarin, nonsteroidal anti-inflammatory drugs (NSAIDs), and other blood-thinning drugs.

On rare occasions, SSRIs can cause an accumulation of high serotonin levels, often when combined with other drugs designed to raise serotonin levels. This severe drug reaction is known as serotonin syndrome.

Given the complexity of mental health disorders, side effects are just one of the significant barriers to finding the right SSRI. 

Finding the Right SSRI

Because the quest to find the right SSRI can be trial-and-error, most people must try several different drugs before finding the one that produces the best results or giving up.

In these cases, doctors can follow medication algorithms or flow charts outlining a logical progression in determining which medication to prescribe. These algorithms are based on current medical knowledge regarding which type of antidepressant works best for specific individuals.

Brief History of the Development of SSRIs

In 1951, French scientist Paul Charpentier synthesized the first antipsychotic drug, chlorpromazine. And just 10 years later, chlorpromazine was used by around 50 million people under the name brand Thorazine, produced by Smith-Kline & French. The widespread use of this drug enabled the future discovery of anxiety and depression medications.

This milestone discovery represented a turning point in the practice of psychiatry, leading to a psychopharmacological revolution and the development of safer drugs like SSRIs.

In 1988, Eli Lilly and Company introduced Prozac as a treatment for clinical depression, establishing a new class of safer and more effective antidepressants. Previously available antidepressants were accompanied by numerous adverse health effects and required extensive monitoring.

Notably, Prozac's role in reshaping the public perception of mental disorders redefined the concept of clinical depression and began to direct psychiatry away from psychotherapy and toward biological treatment.

A better understanding of the fundamental relationship between brain chemistry and depression could lead to significant advances in treating mental disorders.

Researchers at the Stanford University School of Medicine used brain scans and early-life trauma indicators, such as abuse or neglect, to predict whether antidepressants would be beneficial in helping patients recover from depression with 80 percent accuracy.

Methods like this show how precision health — a broader form of precision medicine — can reimagine medicine by focusing on predicting, preventing, and curing diseases and tailoring healthcare to each patient's unique biology and life circumstances.

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