Generic Name

Escitalopram

Mechanism

• Selective serotonin reuptake inhibition (SSRI):
• Escitalopram binds with high affinity to the serotonin transporter (SERT) in presynaptic neurons.
• It blocks serotonin re‑uptake, increasing extracellular serotonin concentration throughout the central nervous system.
• Minimal off‑target activity:
• Little affinity for histamine, adrenergic, cholinergic, or dopaminergic receptors, contributing to its favorable side‑effect profile.

Pharmacokinetics

• Absorption:
• Oral bioavailability ~80 % (reduced by cimetidine inhibition of CYP2C19).
• Peak plasma concentration at ~5–6 h post‑dose.
• Distribution:
• Protein binding ~88 %.
• Volume of distribution ≈ 3–4 L/kg.
• Metabolism:
• Primarily CYP2C19 → 2‑hydroxy‑escitalopram (inactive).
• Minor CYP3A4 contribution.
• Elimination:
• Half‑life 27–32 h (steady‑state ~4 days).
• 84 % renal excretion (mostly unchanged).
• Special populations:
• Elderly: dose adjustments not essential; monitor renal function.
• Moderate hepatic impairment: ↓AUC ≈ 30 %; consider dose reduction.
• Pregnancy: FDA pregnancy category C; limited data suggest minimal teratogenicity but cross‑placental transfer.

Indications

Contraindications

• Contraindicated:
• Serotonin Syndrome risk: concurrent MAOIs or serotonergic agents (e.g., tramadol, linezolid, St. John’s wort).
• Known hypersensitivity to the drug or any excipients.
• Warnings:
• Suicidal ideation: FDA boxed warning in patients ≤24 yrs; monitor in first 6 weeks.
• QT prolongation: Rare, but caution with other QT‑long‑acting drugs or baseline >440 ms.
• Drug interactions:
• Cimetidine ↑ escitalopram AUC; adjust dose.
• Warfarin → slight INR elevation.
• Precautions:
• Pregnancy: Use only if benefits outweigh risks.
• Pediatric use (≥6 yrs): Approved in GAD; monitor growth parameters.

Dosing

• Starting dose: 10 mg PO once daily (morning).
• Titration: 10 mg increments up to a maximum of 20 mg/day, but most patients respond at 10–15 mg.
• Dose Delayed (>1 week): Can increase dosing by 5–10 mg if inadequate response.
• Long‑acting dosing: 1‑2 weeks—continue 10 mg to avoid withdrawal.
• Abrupt discontinuation: Avoid; consider taper over 4–6 weeks to prevent discontinuation syndrome.
• Renal impairment: No dose change necessary, but monitor for accumulation.

Adverse Effects

Common (≤30 % incidence)
• Nausea, dry mouth, insomnia, headache, diarrhea, sexual dysfunction (erectile dysfunction, decreased libido).
• Somnolence or fatigue (often early in therapy).

Serious (≤1 % incidence)
• Serotonin Syndrome: agitation, hyperthermia, clonus.
• Suicidal thoughts/behaviors (especially in <25 yrs).
• QT prolongation (rare).
• Severe GI bleeding (in patients on NSAIDs or anticoagulants).

Discontinuation Syndrome
• Irritability, flu‑like symptoms, sensory disturbances (coasting, electric shock). Occurs most if stopped abruptly before 4 weeks of therapy.

Monitoring

• Baseline:
• Clinical assessment of depression/anxiety scores (HAM-D, GAD‑7).
• Vital signs, CBC, CMP.
• ECG if history of QTc dysrhythmia.
• Consider baseline TSH if patient >60 yrs or history of thyroid disease.
• After Initiation:
• Reassess within 2–4 weeks.
• Monitor suicidal ideation (especially in adolescents).
• Evaluate adherence, side effects, and dose tolerability.
• Bi‑annual:
• Routine labs for patients on prolonged therapy >6 months.
• Toxicity evaluation only if symptomatic.

Clinical Pearls

• Potency advantage: Escitalopram is ~3–6× more potent than citalopram, allowing lower starting doses (10 mg vs 20 mg) and improved tolerability.
• Minimal CYP450 interactions: Unlike many SSRIs, escitalopram’s metabolism is largely via CYP2C19, making it a better choice for poly‑pharmacy patients on hepatic enzyme inducers or inhibitors.
• Early titration: Women with GAD often benefit from early dose steps (10 → 20 mg) within 4 weeks without increased side‑effects.
• Discontinuation warning: A “methadone‑type” weaning schedule (reduce by 25 % every 1–2 weeks) reduces withdrawal headaches and dysphoria.
• Pregnancy‑related: Though data are limited, escitalopram crosses the placenta and has been detected in breastmilk; plan follow‑up and weigh benefits for postpartum depression.
• Adherence cue: Taking the pill with a light snack can help mitigate nausea that commonly occurs in the first week.
• Drug‑interactions to flag: Cimetidine, fluvoxamine, and other MAOIs—all may elevate escitalopram serum levels; readjust dosing accordingly.

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• These points form a concise, high‑yield reference for medical students and prescribers seeking rapid, evidence‑based guidance on escitalopram.