Escitalopram mechanism of action – selective serotonin reuptake inhibition and enhanced serotonergic transmission

Escitalopram – Mechanism of Action

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🔍 Introduction

Escitalopram is a widely prescribed antidepressant belonging to the class of Selective Serotonin Reuptake Inhibitors (SSRIs). It is the S-enantiomer of citalopram and is considered one of the most selective SSRIs available.

Escitalopram is mainly used to treat:

  • Major depressive disorder (MDD)
  • Generalized anxiety disorder (GAD)
  • Panic disorder and social anxiety disorder (off-label)

Due to its clean pharmacological profile and importance in psychiatry, Escitalopram is frequently tested in exams like GPAT, NEET-PG, NCLEX, and taught in PharmD, MBBS, and B.Pharm curricula.

🧬 Stepwise Mechanism of Action of Escitalopram

  1. Selective Inhibition of Serotonin Transporter (SERT):
    Escitalopram binds with high affinity to the serotonin reuptake transporter (SERT) on presynaptic neurons, preventing reabsorption of serotonin (5-HT) from the synaptic cleft.
  2. Increased Serotonin Levels in Synaptic Cleft:
    Blockade of SERT results in elevated extracellular serotonin levels, especially in brain regions like the limbic system and prefrontal cortex.
  3. Prolonged Serotonin Signaling:
    The increased availability of serotonin leads to enhanced serotonergic neurotransmission, which contributes to mood elevation and anxiety reduction.
  4. Delayed Onset Due to Receptor Desensitization:
    Therapeutic effects usually take 2–4 weeks due to downregulation/desensitization of 5-HT1A autoreceptors, which normally limit serotonin release.
  5. High Selectivity for SERT:
    Unlike other SSRIs, Escitalopram shows minimal affinity for norepinephrine and dopamine transporters or histaminic, muscarinic, and alpha receptors → fewer side effects.

🧪 Pharmacokinetic Parameters of Escitalopram

ParameterValue
Bioavailability~80% (oral)
Onset of Action1–4 weeks (clinical effect)
Half-life~27–32 hours
Protein Binding~56%
MetabolismLiver (via CYP2C19, CYP2D6, CYP3A4)
ExcretionRenal and hepatic routes (mostly metabolites)

💊 Clinical Uses of Escitalopram

  • Major Depressive Disorder (MDD)
  • Generalized Anxiety Disorder (GAD)
  • Panic disorder (off-label)
  • Obsessive-compulsive disorder (OCD, off-label)
  • Social anxiety disorder
  • Premenstrual dysphoric disorder (PMDD, off-label)

⚠️ Adverse Effects of Escitalopram

  • Nausea, insomnia, dry mouth
  • Headache, dizziness
  • Sexual dysfunction (common with SSRIs)
  • Increased risk of suicidal ideation in adolescents
  • QT interval prolongation at high doses
  • Serotonin syndrome (when combined with MAOIs or serotonergic drugs)

🔬 Comparative Analysis: Escitalopram vs Fluoxetine

FeatureEscitalopramFluoxetine
ClassSSRISSRI
Half-life~27–32 hours~2–4 days (long-acting)
Onset of action1–2 weeks2–4 weeks
QT Prolongation riskModerate at high dosesLow
Drug interactionsFewerMore (inhibits CYP2D6)
Use in pregnancyCategory CCategory C

📝 Practice MCQs

Q1. Escitalopram acts by:
A. Inhibiting MAO-A
B. Blocking dopamine receptors
C. Selectively inhibiting serotonin reuptake ✅
D. Enhancing norepinephrine release

Q2. Which transporter does Escitalopram bind to?
A. Dopamine transporter
B. Norepinephrine transporter
C. Serotonin transporter (SERT) ✅
D. GABA transporter

Q3. Clinical response to Escitalopram typically begins in:
A. 12 hours
B. 1–2 days
C. 2–4 weeks ✅
D. Immediately

Q4. Which of the following is a common side effect of Escitalopram?
A. Hepatotoxicity
B. Sexual dysfunction ✅
C. Alopecia
D. Visual hallucinations

Q5. Escitalopram is contraindicated with:
A. NSAIDs
B. MAO inhibitors ✅
C. Antacids
D. Paracetamol

Q6. Escitalopram is metabolized by which cytochrome enzymes?
A. CYP1A2
B. CYP2C19, CYP3A4, CYP2D6 ✅
C. CYP2E1
D. CYP7A1

Q7. Which of the following SSRIs has the highest selectivity for serotonin transporters?
A. Sertraline
B. Paroxetine
C. Escitalopram ✅
D. Fluoxetine

Q8. A rare but serious complication of combining Escitalopram with serotonergic drugs is:
A. Neuroleptic malignant syndrome
B. Serotonin syndrome ✅
C. Hypertensive crisis
D. Malignant hyperthermia

Q9. The action of Escitalopram leads to which of the following clinical effects?
A. Antipsychotic effect
B. Mood stabilization
C. Antianxiety and antidepressant effects ✅
D. Sedation only

Q10. Which of the following is least likely with Escitalopram use?
A. QT prolongation
B. Nausea
C. Sedation ✅
D. Delayed ejaculation

❓FAQs

Q1: Can Escitalopram be used in pregnancy?
Generally avoided unless benefits outweigh risks (Pregnancy Category C).

Q2: How long should Escitalopram be taken for depression?
Minimum of 6 months after symptom resolution; long-term use depends on clinical need.

Q3: Is dose adjustment needed in renal or hepatic impairment?
Yes. Start with lower doses in elderly, liver impairment, or renal dysfunction.

Q4: What is the major advantage of Escitalopram over older antidepressants?
Greater selectivity for SERT → fewer side effects and better tolerability.

📚 References

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