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Selective serotonin reuptake inhibitor (SSRI)

Escitalopram

Escitalopram is a selective serotonin reuptake inhibitor (SSRI) antidepressant used primarily for major depressive disorder and generalized anxiety disorder. It is the S-enantiomer of citalopram, offering greater selectivity and potency at the serotonin transporter. The most testable fact is that escitalopram can cause QT prolongation at higher doses and requires caution in patients with cardiac risk factors.

Practice questionsHigh-yield facts
Drug classSelective serotonin reuptake inhibitor (SSRI)
MechanismInhibits presynaptic serotonin reuptake, increasing synaptic 5-HT levels
Main usesMajor depression, generalized anxiety disorder, panic disorder
Key adverse effectQT prolongation, sexual dysfunction, serotonin syndrome risk
6 min readFor medical studentsUpdated 2026-10-14

Mechanism of action

Escitalopram selectively inhibits the serotonin transporter (SERT) at the presynaptic neuronal membrane, blocking reuptake of serotonin (5-HT) from the synaptic cleft. This increases the availability and duration of serotonin at postsynaptic receptors in the central nervous system.

Escitalopram is the pharmacologically active S-enantiomer of the racemic citalopram. It exhibits approximately 100-fold higher affinity for SERT compared to the R-enantiomer, making it one of the most selective SSRIs available. Unlike older antidepressants, escitalopram has minimal affinity for other neurotransmitter receptors including dopaminergic, adrenergic, cholinergic, and histaminergic systems, which reduces the incidence of certain side effects.

The antidepressant and anxiolytic effects are thought to result from adaptive changes in serotonergic neurotransmission that occur over weeks of treatment, including downregulation of presynaptic 5-HT1A autoreceptors and postsynaptic receptor remodeling. The delayed therapeutic response correlates with these neuroadaptive changes rather than the immediate pharmacological effect on serotonin reuptake.

High-yield for exams
  • Escitalopram is the S-enantiomer of citalopram with greater SERT selectivity and potency
  • Black box warning: increased suicidal ideation in patients under age 24 during initial treatment
  • Dose-dependent QT prolongation; FDA recommends maximum 20 mg daily dose
  • Serotonin syndrome risk increases with MAOIs, triptans, tramadol, and other serotonergic agents
  • Must allow 14-day washout between discontinuing MAOI and starting escitalopram (or vice versa)
  • Sexual dysfunction (decreased libido, anorgasmia) affects 30-50% of patients on SSRIs
  • Increased bleeding risk due to impaired platelet aggregation; caution with NSAIDs and anticoagulants
  • Abrupt discontinuation causes withdrawal syndrome; taper over weeks to prevent dizziness and paresthesias

Indications

Escitalopram is approved for the treatment of:

  • Major depressive disorder (MDD) in adults and adolescents aged 12 years and older
  • Generalized anxiety disorder (GAD) in adults

Off-label uses

Escitalopram is commonly used off-label for:

  • Panic disorder
  • Social anxiety disorder (social phobia)
  • Obsessive-compulsive disorder (OCD)
  • Post-traumatic stress disorder (PTSD)
  • Premenstrual dysphoric disorder (PMDD)
  • Vasomotor symptoms of menopause

Escitalopram is generally considered a first-line pharmacological option for depression and anxiety disorders due to its favorable efficacy and tolerability profile. Clinical response typically begins within 2 to 4 weeks, with maximal benefit often requiring 6 to 12 weeks of continuous therapy.

Pharmacokinetics

Absorption: Escitalopram is well absorbed after oral administration, with bioavailability of approximately 80%. Food does not significantly affect absorption. Peak plasma concentrations occur within 4 to 5 hours.

Distribution: The volume of distribution is approximately 12 to 26 L/kg, indicating extensive tissue distribution. Plasma protein binding is approximately 56%. Escitalopram crosses the blood-brain barrier and is distributed into breast milk.

Metabolism: Escitalopram is metabolized primarily in the liver by CYP2C19, CYP3A4, and CYP2D6 to S-desmethylcitalopram (S-DCT) and S-didesmethylcitalopram (S-DDCT), both of which have minimal pharmacological activity. CYP2C19 is the primary enzyme responsible for N-demethylation.

Elimination: The mean elimination half-life is approximately 27 to 32 hours, allowing once-daily dosing and steady-state achievement in about one week. Approximately 8% is excreted unchanged in urine. Clearance is reduced in elderly patients, hepatic impairment, and poor CYP2C19 metabolizers, necessitating dose adjustments.

Special populations: In patients with hepatic impairment, reduced dosing is recommended. Renal impairment does not significantly affect pharmacokinetics unless severe. Geriatric patients may require lower doses due to reduced clearance.

Adverse effects

Common adverse effects

  • Gastrointestinal: Nausea (most common, usually transient), diarrhea, dry mouth, constipation
  • Neurological: Headache, drowsiness, insomnia, dizziness, fatigue
  • Sexual: Decreased libido, ejaculatory delay, anorgasmia, erectile dysfunction (affects 30-50% of patients)
  • Metabolic: Weight gain, increased appetite
  • Other: Increased sweating, tremor

Serious adverse effects

QT prolongation: Escitalopram causes dose-dependent QT interval prolongation. The FDA recommends a maximum dose of 20 mg daily due to QT risk at higher doses. Caution is required in patients with congenital long QT syndrome, cardiac disease, electrolyte abnormalities (hypokalemia, hypomagnesemia), or those taking other QT-prolonging drugs.

Serotonin syndrome: Life-threatening condition characterized by mental status changes, autonomic instability, and neuromuscular hyperactivity. Risk increases with concomitant use of other serotonergic agents (MAOIs, triptans, tramadol, linezolid, St. John's wort).

Bleeding risk: SSRIs impair platelet aggregation by depleting intraplatelet serotonin. Risk increases with concurrent NSAIDs, aspirin, or anticoagulants. Monitor for gastrointestinal and other bleeding.

Hyponatremia/SIADH: Particularly in elderly patients and those on diuretics. Presents with confusion, seizures, and lethargy.

Activation of mania/hypomania: Screen for bipolar disorder before initiating treatment, as antidepressants may precipitate manic episodes.

Suicidality: Black box warning for increased suicidal thinking and behavior in children, adolescents, and young adults (ages 18-24) during initial treatment. Close monitoring is required, especially during the first few months and after dose changes.

Discontinuation syndrome: Abrupt cessation may cause dizziness, paresthesias, anxiety, confusion, and flu-like symptoms. Taper gradually over weeks to months.

Contraindications and warnings

Absolute contraindications

  • Concomitant use with MAOIs (or within 14 days of discontinuing an MAOI)
  • Use with pimozide (due to QT prolongation risk)
  • Known hypersensitivity to escitalopram or citalopram

Warnings and precautions

Pregnancy and lactation: Escitalopram is FDA pregnancy category C. Third-trimester exposure has been associated with neonatal complications including persistent pulmonary hypertension of the newborn (PPHN), respiratory distress, and poor neonatal adaptation syndrome. Risk-benefit analysis is required. Escitalopram is excreted in breast milk; discuss risks with breastfeeding mothers.

Angle-closure glaucoma: SSRIs can cause mydriasis and precipitate angle-closure attacks in patients with anatomically narrow angles.

Seizure disorders: Use with caution, as SSRIs may lower seizure threshold.

Hepatic impairment: Reduced dosing is recommended due to decreased clearance.

Elderly patients: Increased risk of hyponatremia, falls, and bleeding. Start with lower doses.

Cardiovascular disease: Monitor ECG in patients with cardiac risk factors due to QT prolongation risk. Avoid doses exceeding 20 mg daily.

Drug interactions

Major interactions

MAOIs: Absolute contraindication. Concurrent use or inadequate washout period (minimum 14 days) can cause fatal serotonin syndrome. Allow 14 days after stopping escitalopram before starting an MAOI.

Serotonergic drugs: Increased risk of serotonin syndrome with triptans, tramadol, fentanyl, lithium, St. John's wort, tryptophan, buspirone, amphetamines, and other SSRIs/SNRIs. Linezolid and methylene blue also carry risk.

QT-prolonging drugs: Additive QT prolongation with antiarrhythmics (amiodarone, sotalol), antipsychotics (ziprasidone, haloperidol), macrolide antibiotics (azithromycin, erythromycin), and fluoroquinolones.

Anticoagulants and antiplatelet agents: Increased bleeding risk with warfarin, heparin, aspirin, NSAIDs, and other antiplatelet drugs. Monitor INR closely if combining with warfarin.

CYP2C19 inhibitors: Drugs like omeprazole, cimetidine, and fluconazole reduce escitalopram metabolism, potentially increasing levels and side effects.

Moderate interactions

CNS depressants: Additive sedation with alcohol, benzodiazepines, opioids, and antihistamines.

Diuretics: Increased risk of hyponatremia, especially in elderly patients.

Tamoxifen: SSRIs that inhibit CYP2D6 may reduce conversion of tamoxifen to its active metabolite. Escitalopram has minimal CYP2D6 inhibition compared to paroxetine and fluoxetine.

Clinical pearls

  • Escitalopram versus citalopram: Escitalopram is the active S-enantiomer and is approximately twice as potent as racemic citalopram at equivalent milligram doses. It offers similar efficacy with potentially fewer drug interactions.
  • Time to response: Patients should be counseled that therapeutic effects typically emerge after 2 to 4 weeks, and full benefit may require 6 to 12 weeks. Early discontinuation due to perceived lack of efficacy is a common cause of treatment failure.
  • Sexual dysfunction management: If sexual side effects occur, options include dose reduction, switching to bupropion or mirtazapine, adding bupropion, or scheduling sexual activity before the daily dose.
  • Tapering strategy: To minimize discontinuation syndrome, taper gradually over at least 2 to 4 weeks. Longer tapers (weeks to months) may be necessary for patients on long-term therapy or higher doses.
  • Overdose: Escitalopram has a relatively wide therapeutic index. Overdose may present with serotonin syndrome, seizures, QT prolongation, and altered mental status. Management is supportive with cardiac monitoring and benzodiazepines for seizures.
  • Genetic considerations: CYP2C19 poor metabolizers have significantly reduced clearance and may require lower doses. Pharmacogenetic testing can guide dosing in some cases.
  • Activation syndrome: Some patients, particularly adolescents, may experience increased anxiety, agitation, or restlessness during the first 1 to 2 weeks. This usually resolves but requires monitoring.
  • Comparative efficacy: Meta-analyses suggest escitalopram and sertraline are among the most effective and best-tolerated SSRIs for major depression, making them common first-line choices.

Practice questions

1. A 28-year-old woman with major depressive disorder has been taking escitalopram 10 mg daily for 6 weeks with good symptom control. She now presents to the emergency department with confusion, agitation, tremor, hyperreflexia, diaphoresis, and a temperature of 39.2°C (102.6°F). Her family reports she started taking an over-the-counter cold remedy 2 days ago. Vital signs show BP 160/95 mmHg, HR 115/min. Which of the following medications in the cold remedy most likely caused this reaction?

Answer: A. This patient is presenting with serotonin syndrome, characterized by the triad of mental status changes, autonomic hyperactivity (hypertension, tachycardia, hyperthermia, diaphoresis), and neuromuscular abnormalities (tremor, hyperreflexia, clonus). Dextromethorphan is a common ingredient in cold medications that has serotonergic properties and can precipitate serotonin syndrome when combined with SSRIs like escitalopram. Pseudoephedrine is a sympathomimetic that could raise blood pressure but would not cause the full serotonin syndrome picture. The other options lack significant serotonergic activity.

2. A 45-year-old man with generalized anxiety disorder is started on escitalopram 10 mg daily. Six weeks later, he reports significant improvement in anxiety but complains of delayed ejaculation that is affecting his relationship. Physical examination and laboratory tests, including testosterone, are normal. Which of the following is the most appropriate next step in management?

Answer: B. Sexual dysfunction, including delayed ejaculation, is a common side effect of SSRIs affecting 30-50% of patients. Since the patient has good therapeutic response, abrupt discontinuation would risk relapse of anxiety. Adding bupropion, which has dopaminergic and noradrenergic activity rather than serotonergic effects, can help counteract SSRI-induced sexual dysfunction while maintaining anxiety control. Switching to paroxetine, another SSRI, would likely cause the same problem. Increasing the escitalopram dose would worsen sexual side effects. Urologic evaluation is unnecessary as this is medication-related.

3. A 72-year-old woman on escitalopram 15 mg daily for depression presents with confusion, nausea, and headache of 3 days' duration. She also takes hydrochlorothiazide for hypertension. Vital signs are normal. Laboratory studies show: Sodium 122 mEq/L (normal 135-145), Potassium 4.0 mEq/L, Serum osmolality 255 mOsm/kg (low), Urine osmolality 450 mOsm/kg (inappropriately concentrated), Urine sodium 40 mEq/L. Which of the following best explains this patient's condition?

Answer: B. This patient has hyponatremia with low serum osmolality and inappropriately concentrated urine consistent with SIADH. SSRIs like escitalopram can cause SIADH, particularly in elderly patients and those on diuretics, by potentiating ADH release or action. The combination of escitalopram and hydrochlorothiazide further increases risk. Psychogenic polydipsia would show dilute urine. Acute kidney injury would show elevated creatinine. Adrenal insufficiency typically presents with hyperkalemia and hypotension. Hypothyroidism causes hyponatremia but through different mechanisms and would have other clinical features.

Frequently asked questions

How does escitalopram work?

Escitalopram works by selectively inhibiting the serotonin transporter (SERT) at presynaptic neurons, blocking the reuptake of serotonin from the synaptic cleft. This increases serotonin availability at postsynaptic receptors in the brain. It is the pharmacologically active S-enantiomer of citalopram with approximately 100-fold greater affinity for SERT compared to the R-enantiomer, making it highly selective with minimal effects on other neurotransmitter systems.

What are the side effects of escitalopram?

Common side effects include nausea, headache, drowsiness, insomnia, sexual dysfunction (decreased libido, delayed ejaculation, anorgasmia), dry mouth, increased sweating, and diarrhea. Serious adverse effects include QT prolongation (especially at doses above 20 mg daily), serotonin syndrome when combined with other serotonergic drugs, increased bleeding risk, hyponatremia (particularly in elderly patients), and increased suicidal thoughts in patients under 24 years old. Abrupt discontinuation can cause withdrawal symptoms including dizziness, paresthesias, and flu-like symptoms.

Is escitalopram a controlled substance?

No, escitalopram is not a controlled substance. It is a selective serotonin reuptake inhibitor (SSRI) antidepressant that does not have abuse potential or cause physical dependence in the way controlled substances do. However, it should not be stopped abruptly due to the risk of discontinuation syndrome, and it requires a prescription for use.

Escitalopram vs citalopram — what is the difference?

Escitalopram is the isolated S-enantiomer of racemic citalopram and is approximately twice as potent at equivalent milligram doses. Citalopram contains both the S- and R-enantiomers, but only the S-form is pharmacologically active at the serotonin transporter. Escitalopram offers greater selectivity, potentially fewer drug interactions, and similar efficacy with slightly better tolerability. Both carry risks of QT prolongation, though citalopram has a lower maximum recommended dose (40 mg) compared to escitalopram (20 mg) due to cardiac concerns.

How long does it take for escitalopram to work?

Initial therapeutic effects typically begin to emerge after 2 to 4 weeks of continuous treatment, though some patients may notice subtle improvements in sleep and anxiety within the first week. Full antidepressant benefit often requires 6 to 12 weeks of therapy at an adequate dose. Patients should be counseled about this delayed response to prevent premature discontinuation. If no improvement is seen after 6 to 8 weeks at therapeutic doses, re-evaluation and possible medication change should be considered.

Conditions it is used for

Major depressive disorderGeneralized anxiety disorderPanic disorderSocial anxiety disorderObsessive-compulsive disorderPost-traumatic stress disorder
citalopramsertralinefluoxetineparoxetinevenlafaxinebupropionmirtazapinefluvoxamine

Sources and further reading

DailyMed (FDA labels)StatPearls (NCBI Bookshelf)MedlinePlusWHO ATC/DDD index: N06AB10

Educational content for medical students, prepared by the WhiteCoat Pro editorial team with AI assistance; every page is reviewed by a second AI model for factual errors. It is not medical advice and does not replace the product label, local guidelines or a clinician.