Selective serotonin reuptake inhibitors mnemonic (SSRIs) are prescription medications belonging to the drugs category used to treat a variety of mental health conditions, including depression, anxiety, and obsessive-compulsive disorder (OCD). The following are some uses:

Uses of SSRIs:

• Major depressive disorder
• Generalized anxiety disorder (GAD)
• Panic disorder
• Obsessive-compulsive disorder (OCD)
• Social anxiety disorder
• Posttraumatic stress disorder (PTSD)
• Premenstrual dysphoric disorder (PMDD)
• Bipolar depression
• Bulimia nervosa
• Treatment-resistant depression

1.Meaning of SSRIs

a) Serotonin – The “Feel-Good” Neurotransmitter

Serotonin is a neurotransmitter (chemical messenger in the brain) responsible for mood regulation, emotions, sleep, and appetite. It plays a key role in promoting feelings of well-being and happiness.

When serotonin levels are low, it can lead to depression, anxiety, and mood disorders. Many antidepressant medications aim to increase serotonin levels in the brain to improve mood.

b) Reuptake – The Process of Recycling Neurotransmitters

After serotonin is released from one neuron (nerve cell), it binds to receptors on another neuron to pass along the signal. Once serotonin has done its job, the first neuron “reabsorbs” it through a process called reuptake, which reduces the amount of serotonin available in the brain.
If too much serotonin is reabsorbed, there might not be enough left in the brain to regulate mood effectively, contributing to depression.

c) Inhibition – Blocking Reuptake to Increase Serotonin Levels

This is where SSRIs (Selective Serotonin Reuptake Inhibitors) come in. They block the reuptake of serotonin, preventing the brain from absorbing too much of it. This increases the amount of serotonin available in the synapses (the gaps between neurons), improving mood and alleviating symptoms of depression.

d) Selective – Targeting Only Serotonin

SSRIs are “selective” because they primarily affect serotonin rather than other neurotransmitters like dopamine or norepinephrine. This makes them different from older antidepressants, which affected multiple neurotransmitters and often caused more side effects.

2. Background & History of SSRIs

Before SSRIs, older tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) were used to treat depression, but they had significant side effects.

In the 1970s–1980s, researchers discovered that serotonin played a major role in depression.

The first SSRI, fluoxetine (Prozac), was developed in 1987 and revolutionized depression treatment by being more effective and having fewer side effects than older antidepressants.

Since then, several SSRIs have been introduced and are now widely used for depression, anxiety, PTSD, OCD, and panic disorders.

3. Mnemonic to Remember SSRIs

An easy mnemonic to recall common SSRIs is EFSPC:
“Effective For Sadness, Panic, & Compulsions”

• E → Escitalopram (Lexapro)
• F → Fluoxetine (Prozac)
• S → Sertraline (Zoloft)
• P → Paroxetine (Paxil)
• C → Citalopram (Celexa)

Above are some of the most commonly prescribed SSRIs.

4. Clinical Uses of SSRIs

Apart from depression, SSRIs are used to treat:

✔ Generalized Anxiety Disorder (GAD)
✔ Obsessive-Compulsive Disorder (OCD)
✔ Post-Traumatic Stress Disorder (PTSD)
✔ Panic Disorder
✔ Social Anxiety Disorder
✔ Premenstrual Dysphoric Disorder (PMDD)

5. How Long Do SSRIs Take to Work?

SSRIs do not work immediately. It usually takes 2 to 6 weeks for the full therapeutic effect. During this time, some people may experience mild side effects before noticing improvements in mood.

6. Side Effects of SSRIs

While SSRIs are generally well-tolerated, they can cause:

• Nausea
• Insomnia or drowsiness
• Sexual dysfunction
• Weight changes
• Increased risk of suicidal thoughts (in young adults, early in treatment)
• Serotonin syndrome (rare but serious condition due to excessive serotonin buildup)

7. Are SSRIs Addictive?

SSRIs are not addictive, but suddenly stopping them can cause withdrawal-like symptoms called SSRI discontinuation syndrome, leading to dizziness, mood swings, and flu-like symptoms. It is always advised to taper off SSRIs gradually under a doctor’s guidance.

8. Pharmacogenomics & SSRIs – How Genetics Affects Their Effectiveness

Not everyone responds to SSRIs the same way. Genetic variations in liver enzymes (CYP2C19 & CYP2D6) can affect how SSRIs are metabolized. Some people may:

• Metabolize SSRIs too fast → Drug is less effective.
• Metabolize SSRIs too slow → Drug builds up, increasing side effects.

Pharmacogenomic testing helps doctors personalize SSRI treatment based on a person’s genetics, improving efficacy and minimizing side effects.

9. Summary of Selective Serotonin Reuptake Inhibitors Mnemonic

• Selective: Primarily affects serotonin.
• Serotonin: A neurotransmitter regulating mood.
• Reuptake Inhibitor: Blocks serotonin absorption, increasing its availability.
• Used for: Depression, anxiety, OCD, PTSD, and panic disorders.
• Common SSRIs: Fluoxetine, Sertraline, Escitalopram, Paroxetine, Citalopram.

Takes 2-6 weeks to work, side effects are usually mild, and pharmacogenomics can help tailor treatment.

Most Common SSRIs in the USA

The following SSRIs are widely prescribed:

✔ Fluoxetine (Prozac)
✔ Sertraline (Zoloft)
✔ Escitalopram (Lexapro)
✔ Citalopram (Celexa)
✔ Paroxetine (Paxil, Pexeva)
✔ Fluvoxamine (Luvox) – primarily used for OCD

Liver Enzymes Responsible for SSRI Metabolism

SSRIs are primarily metabolized in the liver by enzymes from the cytochrome P450 (CYP450) system. However, the specific enzymes vary by drug:

SSRI	Primary Metabolizing Enzymes	Metabolism Details
Fluoxetine (Prozac)	CYP2D6, CYP2C19, CYP3A4 (major contributing enzymes)	Strong CYP2D6 inhibitor, long half-life (~4-6 days).
Sertraline (Zoloft)	CYP2C19, CYP2B6 (major), CYP3A4	Moderate CYP2D6 inhibition, active metabolite (norsertraline).
Escitalopram (Lexapro)	CYP2C19, CYP3A4 (minor CYP2D6)	CYP2C19 poor metabolizers may need dose adjustments.
Citalopram (Celexa)	CYP2C19, CYP3A4 (minor CYP2D6)	CYP2C19 poor metabolizers at risk for prolonged QT interval.
Paroxetine (Paxil)	CYP2D6	Strong CYP2D6 inhibitor, short half-life (~24 hours).
Fluvoxamine (Luvox)	CYP1A2, CYP2C19, CYP3A4	Strong CYP1A2 inhibitor, significant drug interactions.

Important: Side effects of incorrect dosing may range from slight to severe, including fatalities. Genome based dosing is possible with the help of a non-invasive PGx test (pharmacogenomics test).

Why Does SSRI Metabolism Matter?

Drug-Drug Interactions: Some SSRIs (like fluoxetine and paroxetine) strongly inhibit CYP2D6, affecting the metabolism of other medications like codeine, tramadol, or certain beta-blockers.

Genetic Variability: People with CYP2C19 or CYP2D6 genetic variants may metabolize SSRIs too quickly (reducing drug effectiveness) or too slowly (increasing side effects).

Dose Adjustments: Based on a patient’s metabolism, a lower or higher SSRI dose may be needed for optimal efficacy and tolerability.

Pharmacogenomic Testing for SSRIs

Since genetic differences impact how people metabolize Selective Serotonin Reuptake inhibitors mnemonic (SSRIs), pharmacogenomic testing, commonly known as PGx testing can help doctors administer tailored doses to increase treatment efficacy and decrease adverse effects.

• CYP2D6 Poor Metabolizers: May experience stronger side effects with fluoxetine or paroxetine.
• CYP2C19 Poor Metabolizers: May need a lower dose of citalopram or escitalopram to prevent excessive drug accumulation.

PGx testing from RPh LABS provides insights into your genetic makeup, showing what type of metabolizer you are and how your body may respond to 250+ medications. Although the list is extensive, mental health medications are mainly included therein. Here is how this pharmacogenetic testing / Pharmacogenomics testing works.

References:

https://pmc.ncbi.nlm.nih.gov/articles/PMC8395812/
https://www.ncbi.nlm.nih.gov/books/NBK554406/
https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.833217/