Adult: 10 mg once daily, may be increased after at least 1 week to Max of 20 mg once daily depending on patient response. Elderly: Initially, 5 mg once daily, may be increased to Max of 10 mg daily depending on patient response. Child: ≥12 years 10 mg once daily, may be increased after at least 3 weeks to 20 mg once daily depending on patient response. Treatment recommendations may vary among countries or individual products. Refer to specific product guidelines.
Adult: 10 mg once daily, may be increased after at least 1 week to Max of 20 mg once daily depending on patient response. Elderly: Initially, 5 mg once daily, may be increased to Max of 10 mg daily depending on patient response.
Oral Social anxiety disorder
Adult: 10 mg once daily, may be decreased to 5 mg or increased to Max of 20 mg once daily after at least 1 week depending on patient response. Elderly: Initially, 5 mg once daily, may be increased to Max of 10 mg daily depending on patient response.
Oral Panic disorder with or without agoraphobia
Adult: Initially, 5 mg once daily for 1 week, then increased to 10 mg once daily; may be further increased up to Max of 20 mg daily depending on patient response. Elderly: Initially, 5 mg once daily, may be increased to Max of 10 mg daily depending on patient response.
Special Patient Group
Pharmacogenomics:
Escitalopram is extensively metabolised mainly by CYP2C19 isoenzyme to S-desmethylcitalopram, which confers less serotonin reuptake inhibition. The CYP2C19 gene is highly polymorphic and interindividual differences in pharmacokinetic parameter values and treatment outcomes with SSRIs are associated with CYP2C19 polymorphisms. Genetic testing may be considered as this may provide the potential benefit of determining patients who are at an increased risk of experiencing adverse reactions or treatment failure.
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline as of August 2015:
Phenotype and Genotype
Implication
Recommendation
CYP2C19 ultrarapid metaboliser
Patients carrying 2 increased function alleles or 1 normal functional allele and 1 increased function allele e.g. *17/*17, *1/*17
Increased metabolism as compared to extensive metabolisers (normal metabolisers). Lower plasma concentrations may increase the possibility of pharmacotherapy failure.
Consider using an alternative agent that is not primarily metabolised by CYP2C19.
CYP2C19 intermediate metaboliser
Patients carrying 1 normal functional allele or 1 increased function allele and 1 non-functional allele e.g. *1/*2, *1/*3, *2/*17
Reduced metabolism as compared to extensive metabolisers.
Initiate treatment with the recommended initial dose.
CYP2C19 poor metaboliser
Patients carrying 2 non-functional alleles e.g. *2/*2, *2/*3, *3/*3
Greatly reduced metabolism as compared to extensive metabolisers. Higher plasma concentrations may increase the possibility of adverse effects.
Consider a 50% reduction of the recommended initial dose and titrate to response, or select an alternative agent not primarily metabolised by CYP2C19.
Royal Dutch Pharmacists Association - Pharmacogenetics Working Group (DPWG) Guideline as of November 2018:
Phenotype
Implication
Recommendation
CYP2C19 intermediate metaboliser
Increased risk of developing QT prolongation and torsades de pointes.
Do not exceed the recommended doses (75% of the standard Max dose): Adults: <65 years 15 mg daily; ≥65 years 7.5 mg daily.
CYP2C19 poor metaboliser
Increased risk of developing QT prolongation and torsades de pointes and increased risk of switching to another antidepressant.
Do not exceed the recommended doses (50% of the standard Max dose): Adults: <65 years 10 mg daily; ≥65 years 5 mg daily.
Additionally, for CYP2C19 poor metabolisers, some product labelling of escitalopram recommends an initial dose of 5 mg daily during the 1st 2 weeks and may be increased to 10 mg daily according to individual response.
Dosage or treatment recommendations may vary among countries. Refer to specific country guidelines for the appropriate clinical recommendations.
Hepatic Impairment
Mild to moderate: Initially, 5 mg once daily for 2 weeks, then may be increased to 10 mg daily depending on patient response.
Administration
May be taken with or without food.
Contraindications
Known QT interval prolongation or congenital long QT syndrome. Concomitant use with QT interval prolonging agents (e.g. pimozide), linezolid or IV methylthioninium chloride (also known as methylene blue). Concomitant use with or within 14 days of discontinuing MAOIs used to treat psychiatric disorders.
Special Precautions
Patient with history of seizure disorder or condition predisposing to seizures (e.g. brain damage, alcoholism), controlled epilepsy; history of mania/hypomania or suicide-related events, significant degree of suicidal ideation; diabetes, known bleeding tendencies, bradycardia, recent acute MI, uncompensated heart failure, electrolyte disturbances (e.g. hypokalaemia, hypomagnesaemia), angle-closure glaucoma or history of glaucoma, metabolic disease. Avoid abrupt withdrawal. Avoid use in patients with unstable epilepsy. Concomitant electroconvulsive therapy. CYP2C19 ultrarapid, intermediate, or poor metabolisers. Hepatic and severe renal (CrCl <30 mL/min) impairment. Children and elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Suicidal ideation or behaviour (particularly in children and young adults), withdrawal symptoms, paradoxical anxiety, seizures; akathisia or psychomotor restlessness; may precipitate hypomania or mania; cutaneous bleeding abnormalities (e.g. ecchymoses, purpura), QT interval prolongation, ventricular arrhythmia (including torsades de pointes), mydriasis, acute angle-closure glaucoma, increased risk of bone fractures, sexual dysfunction (e.g. decreased libido, anorgasmia, ejaculation disorder, impotence). Rarely, hyponatraemia. Gastrointestinal disorders: Nausea, diarrhoea, vomiting, constipation, dry mouth. General disorders and administration site conditions: Fatigue, pyrexia. Investigations: Weight increased. Metabolism and nutrition disorders: Decreased or increased appetite. Musculoskeletal and connective tissue disorders: Arthralgia, myalgia. Nervous system disorders: Headache, dizziness, paraesthesia, tremor, somnolence. Psychiatric disorders: Abnormal dreams, insomnia. Respiratory, thoracic and mediastinal disorders: Sinusitis, yawning. Skin and subcutaneous tissue disorders: Increased sweating. Potentially Fatal: Serotonin syndrome, haemorrhage.
PO: Z (Risk of postpartum haemorrhage, persistent pulmonary hypertension in infant and neonatal withdrawal/toxicity in late pregnancy use. Monitor closely.)
Patient Counseling Information
This drug may cause drowsiness or impair judgement or skills; if affected, do not drive or operate machinery.
Monitoring Parameters
Screen patients for bipolar disorder before initiating treatment. Closely monitor for clinical worsening, suicidal behaviour or ideation, or unusual behavioural changes, particularly during the initial 1-2 months of treatment and at times of dosage adjustments. Monitor electrolytes (e.g. K, Mg, Na) and liver and renal function tests at baseline and as clinically indicated. Assess for signs or symptoms of serotonin syndrome (e.g. mental status changes, tachycardia, labile blood pressure, diaphoresis, tremor, rigidity, seizures) during treatment and withdrawal symptoms (e.g. dizziness, sensory disturbances, agitation, irritability, sleep disturbances) upon discontinuation.
Overdosage
Symptoms: Dizziness, tremor, agitation, nausea, vomiting, hypotension, tachycardia, prolonged QT interval, arrhythmia, hypokalaemia, and hyponatraemia. Rarely, serotonin syndrome, convulsion, and coma. Management: Symptomatic and supportive treatment. Perform gastric lavage as soon as possible and consider administering activated charcoal. Establish and maintain an airway and establish adequate oxygenation and respiratory function. Monitor cardiac function and vital signs. ECG monitoring is recommended in case of overdose in patients with CHF or bradyarrhythmias, patients concomitantly receiving agents that prolong the QT interval, or those with altered metabolism.
Drug Interactions
Increased risk of bleeding with oral anticoagulants (e.g. warfarin), antiplatelet agents (e.g. ticlopidine, aspirin, dipyridamole), atypical antipsychotics, and NSAIDs. May increase the risk of serotonin syndrome with other serotonergic agents (e.g. TCA, triptans, opioids, tryptophan, lithium, buspirone). May increase the risk of seizures with other antidepressants (e.g. other SSRIs), neuroleptics (e.g. thioxanthenes), mefloquine, tramadol, and bupropion. Increased serum concentration with CYP2C19 inhibitors (e.g. omeprazole, fluconazole, fluvoxamine) or cimetidine. May increase the plasma concentrations of CYP2D6 substrates (e.g. metoprolol, desipramine). Potentially Fatal: Enhanced serotonergic effect with MAOIs including linezolid and IV methylthioninium chloride, which may result in serotonin syndrome. May increase the risk of QT interval prolongation with pimozide and other drugs prolonging QT interval (e.g. class IA and III antiarrhythmics, phenothiazines, haloperidol, astemizole, mizolastine, halofantrine, sparfloxacin, moxifloxacin).
Food Interaction
May increase the risk of serotonin syndrome with St. John's wort.
Action
Description: Mechanism of Action: Escitalopram is the S-enantiomer of the racemic derivative citalopram, which selectively inhibits the reuptake of serotonin, thus potentiating serotonergic activity in the CNS. It has little to no effect on norepinephrine or dopamine reuptake; very low or no affinity for serotonergic (5-HT1-7), α- and β-adrenergic, dopamine (D1-5), histamine (H1-3), muscarinic (M1-5), benzodiazepine, and opioid receptors, or various ion channels including K, Na, Ca, and chloride channels. Onset: Anxiety disorders: Within 2 weeks. Depression: Within 1-2 weeks. Pharmacokinetics: Absorption: Almost completely absorbed. Bioavailability: Approx 80%. Time to peak plasma concentration: Approx 5 hours. Distribution: Crosses the placenta and enters breast milk. Volume of distribution: Approx 20 L/kg. Plasma protein binding: Approx 56%. Metabolism: Extensively metabolised in the liver mainly by CYP2C19 and CYP3A4 to S-desmethylcitalopram (S-DCT), which is further metabolised by CYP2D6 to S-didesmethylcitalopram (S-DDCT). Excretion: Via urine (8% as unchanged drug; 10% as S-DCT). Elimination half-life: Approx 27-32 hours.
Chemical Structure
Escitalopram Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 146570, Escitalopram. https://pubchem.ncbi.nlm.nih.gov/compound/Escitalopram. Accessed Feb. 28, 2023.
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