Selective serotonin reuptake inhibitor

Class of antidepressants

Selective serotonin reuptake inhibitors (SSRIs) are a class of pharmacological agents primarily used to treat depression, anxiety disorders, and other psychological conditions. SSRIs work by increasing serotonin levels in the brain by inhibiting its reuptake, thereby improving mood and emotional stability.

SSRIs are among the most commonly prescribed antidepressants worldwide due to their efficacy, tolerability, and relatively mild side-effect profile. Popular SSRIs include:

• Fluoxetine (Prozac)
• Sertraline (Zoloft)
• Paroxetine (Paxil)
• Citalopram (Celexa)
• Escitalopram (Lexapro)
• Fluvoxamine (Luvox)

Mechanism of Action

SSRIs function by blocking the serotonin transporter (SERT), which prevents serotonin reuptake at synapses. This increases serotonin availability in the synaptic cleft, thereby enhancing neurotransmission in the serotonergic system, which is crucial for mood regulation, emotion, and cognition.

Unlike tricyclic antidepressants (TCAs) or monoamine oxidase inhibitors (MAOIs), SSRIs specifically target serotonin without significantly affecting norepinephrine or dopamine, which contributes to their lower side effect profile.

Therapeutic Uses

SSRIs are prescribed for several psychiatric and psychological conditions, including:

1. Major Depressive Disorder (MDD)

SSRIs are the first-line pharmacological treatment for moderate to severe depression. They are recommended when psychotherapy alone is insufficient. Studies indicate that SSRIs can significantly reduce depressive symptoms and prevent relapse.

2. Anxiety Disorders

SSRIs are widely used for treating generalized anxiety disorder (GAD), social anxiety disorder (SAD), and panic disorder (PD). Their efficacy in reducing excessive worry and fear makes them a primary treatment option.

3. Obsessive-Compulsive Disorder (OCD)

SSRIs, particularly fluvoxamine, fluoxetine, and sertraline, are FDA-approved for OCD treatment. Higher doses may be required for obsessive-compulsive symptoms, and combination with cognitive behavioral therapy (CBT) improves outcomes.

4. Post-Traumatic Stress Disorder (PTSD)

Fluoxetine and paroxetine are the only FDA-approved SSRIs for PTSD. They are used to reduce intrusive thoughts, nightmares, and hyperarousal symptoms.

5. Eating Disorders

SSRIs, particularly fluoxetine, are prescribed for bulimia nervosa and binge eating disorder. They help reduce compulsive eating behaviors and improve impulse control.

6. Premenstrual Dysphoric Disorder (PMDD)

Sertraline and fluoxetine are commonly prescribed for PMDD, a severe form of premenstrual syndrome (PMS) characterized by mood swings, irritability, and depression.

Side Effects

While SSRIs are generally well-tolerated, they can cause side effects, particularly in the first few weeks of treatment. Common side effects include:

• Gastrointestinal issues – nausea, diarrhea, dry mouth
• Neurological symptoms – headache, dizziness, insomnia, drowsiness
• Sexual dysfunction – reduced libido, anorgasmia, erectile dysfunction
• Weight changes – slight weight gain or loss
• Emotional blunting – reduced emotional responsiveness

Most side effects subside over time, but persistent or severe reactions should be reported to a healthcare provider.

Discontinuation Syndrome

Stopping SSRIs abruptly can lead to withdrawal-like symptoms known as SSRI Discontinuation Syndrome. Symptoms include:

• Flu-like symptoms
• Dizziness, nausea
• Sensory disturbances ("brain zaps")
• Anxiety, irritability
• Insomnia

To prevent withdrawal effects, SSRIs should be tapered gradually under medical supervision.

Drug Interactions

SSRIs interact with multiple medications, increasing the risk of serotonin syndrome, a potentially life-threatening condition. Patients should avoid:

• Other antidepressants:
• Monoamine oxidase inhibitors (MAOIs)
• Tricyclic antidepressants (TCAs)
• Serotonin-norepinephrine reuptake inhibitors (SNRIs)
• Pain medications:
• Tramadol
• Meperidine (Demerol)
• Other interactions:
• St. John's Wort – Increases serotonin levels, leading to serotonin syndrome
• MDMA (Ecstasy) – Can cause dangerous serotonin spikes
• Dextromethorphan – Found in cough medicines, may trigger interactions

Special Considerations

Pregnancy and Breastfeeding

• Some SSRIs, such as fluoxetine and sertraline, are considered relatively safe during pregnancy.
• However, paroxetine has been associated with congenital heart defects.
• SSRIs can pass into breast milk, but are generally considered safe for breastfeeding mothers.

Suicide Risk

• In young adults (under 25), SSRIs may increase suicidal thoughts during the first few weeks of treatment.
• Close monitoring is recommended during initial treatment and dosage adjustments.

Comparison with Other Antidepressants

Comparison of SSRIs with Other Antidepressants

Class	Example Drugs	Mechanism of Action	Side Effect Profile	Special Considerations
SSRIs	Fluoxetine, Sertraline	Selective serotonin reuptake inhibition	Mild, well-tolerated	First-line for depression and anxiety
SNRIs	Venlafaxine, Duloxetine	Inhibits serotonin & norepinephrine reuptake	Increased blood pressure	Used in depression & chronic pain
TCAs	Amitriptyline, Nortriptyline	Blocks serotonin & norepinephrine reuptake	More sedation, weight gain	Effective but more side effects
MAOIs	Phenelzine, Selegiline	Blocks monoamine oxidase (MAO)	Dietary restrictions (tyramine)	Used for treatment-resistant depression

See Also

• Serotonin
• Depression (mental illness)
• Anxiety disorder
• Antidepressant

External Links

Classification	ICD-10: N06.A MeSH: D017367
External resources	eMedicine: psych/selective-serotonin-reuptake-inhibitor

The following are antidepressant subclasses and drugs

MAO Inhibitors Isocarboxazid, Phenelzine, Tranylcypromine

SNRIs Duloxetine, Levomilnacipran, Venlafaxine

SSRIs Citalopram, Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline, Vilazodone, Vortioxetine

Tricyclics Amitriptyline, Amoxapine, Clomipramine, Desipramine, Doxepin, Imipramine, Nortriptyline, Protriptyline, Trimipramine

Miscellaneous Bupropion, Flibanserin, Mirtazapine, Nefazodone, Trazodone

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