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 increase the dose 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 increase the dose 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 further increase the dose up to Max of 20 mg daily depending on patient response. Elderly: Initially, 5 mg once daily, may increase the dose to 10 mg daily depending on patient response.
Special Patient Group
Escitalopram is extensively metabolised by CYP2C19 to S-desmethylcitalopram and further metabolised by CYP2D6 to S-didesmethylcitalopram. Interindividual differences in pharmacokinetic parameter values and treatment outcomes with escitalopram are associated with CYP2C19 or CYP2D6 polymorphisms. Additionally, pharmacodynamic mechanisms may be involved in the association between CYP2C19 and antidepressant response, as CYP2C19 activity was reported to influence central neurotransmitters and neurotrophins relevant to antidepressant mechanisms of action. The enzyme activity of CYP2C19 may enable clinicians to predict the appropriate dose of escitalopram based on gene type. Limited studies are available in the clinical relevance of CYP2D6 enzyme in relation to the safety or efficacy of escitalopram.
CYP2C19 allele frequency may vary depending on race or ethnic background. For example, CYP2C19*2 allele is the main inactive variant in Caucasians having a frequency of approx 15% while CYP2C19*3 variant is prevalent in Asian populations and is essentially absent in Caucasians. Both alleles account for the majority of the poor metaboliser alleles. The prevalence of CYP2C19*17 allele is 18-27% in various Caucasian groups; 18% in Swedish or Ethiopian populations, 4% in the Chinese population, 26% in Polish population and 22% in Norwegian population.
Patients who are carriers of 2 increased functional alleles or 1 normal function allele and 1 increased function allele (e.g. *17/*17, *1/*17) may have increased metabolism and lower plasma concentrations of escitalopram resulting to treatment failure. Clinical Pharmacogenetics Implementation Consortium (CPIC) recommends the use of an alternative drug which is not predominantly metabolised by CYP2C19.
Patients who are carriers of 2 normal function alleles (e.g. *1/*1) may have normal metabolism of escitalopram. CPIC recommends initiation of therapy with the recommended starting dose.
Patients who are carriers of 1 normal function allele or 1 increased function allele and 1 non-functional allele (e.g. *1/*2, *1/*3, *2/*17) may have reduced metabolism as compared to extensive metabolisers. However, CPIC recommends initiation of therapy with the recommended starting dose.
Patients who are carriers of 2 non-functional alleles (e.g. *2/*2, *2/*3, *3/*3) may have greatly reduced metabolism as compared to extensive metabolisers, resulting in higher plasma concentrations of escitalopram and may increase risk of adverse effects (e.g. neurological, sexual, gastrointestinal). CPIC recommends 50% dose reduction of recommended starting dose and titrate to response or using an alternative drug which is not predominantly metabolised by CYP2C19. However, a recent study showed that poor metabolisers may still benefit from the standard dose of escitalopram and may have higher symptom improvement and remission probability as compared to extensive metabolisers.
Mild to moderate: Initially, 5 mg once daily for 2 weeks, may increase dose to 10 mg daily depending on patient response.
May be taken with or without food.
Known QT interval prolongation or congenital long QT syndrome, unstable epilepsy. Concomitant use of QT interval prolonging agents (e.g. pimozide) and MAOIs (or within 14 days of use).
Patient with history of seizure disorder or conditions predisposing to seizures (e.g. brain damage, alcoholism); history of mania/hypomania, suicide-related events, suicidal ideation; diabetes, bleeding tendencies, bradycardia, recent MI, decompensated heart failure, electrolyte disturbances (e.g. hypokalaemia), metabolic disease. CYP2C19 ultrarapid or poor metabolisers. Hepatic and severe renal impairment. Elderly. Pregnancy and lactation. Avoid abrupt withdrawal. Concomitant electroconvulsive therapy.
Significant: Withdrawal syndrome, anxiety, suicide-related events, worsening of depressive symptoms, hypomania or mania, bleeding abnormalities (e.g. ecchymoses, purpura, haematoma, epistaxis), akathisia, QT interval prolongation, ventricular arrhythmia, torsade de pointes, mydriasis, narrow-angle glaucoma, bone fractures, sexual dysfunction. Rarely, hyponatraemia. Gastrointestinal disorders: Nausea, diarrhoea, vomiting, constipation, dry mouth. General disorders and admin site conditions: Fatigue, pyrexia. Metabolism and nutrition disorders: Decreased or increased appetite, increased weight. Musculoskeletal and connective tissue disorders: Arthralgia, myalgia. Nervous system disorders: Headache, dizziness, paraesthesia, tremor. Psychiatric disorders: Restlessness, abnormal dreams, insomnia, somnolence. Reproductive system and breast disorders: Decreased libido, anorgasmia, ejaculation disorder, impotence. Respiratory, thoracic and mediastinal disorders: Sinusitis, yawning. Skin and subcutaneous tissue disorders: Increased sweating. Potentially Fatal: Serotonin syndrome, suicidal ideation or behaviour, haemorrhage.
PO: Z (SSRI use in late pregnancy is associated with increased risk of postpartum haemorrhage, persistent pulmonary hypertension in the newborn, and neonatal withdrawal and toxicity. Monitor for these adverse effects when escitalopram is required during pregnancy.)
Patient Counseling Information
This drug may impair cognitive or motor performance, if affected, do not drive or operate machinery.
Re-evaluate treatment periodically. Monitor for clinical worsening, suicidal behaviour or ideation and unusual changes in behaviour. Monitor electrolytes (e.g. K, Mg, Na), liver and renal function at baseline and as clinically indicated; signs of serotonin syndrome (e.g. mental status changes, autonomic instability, seizures) during treatment and withdrawal syndrome (e.g. dizziness, sensory disturbances, agitation, sleep disturbances) upon discontinuation.
Symptoms: Dizziness, tremor, agitation, nausea, vomiting, hypotension, tachycardia, somnolence, prolonged QT interval, arrhythmia, hypokalaemia, hyponatraemia. Rarely, acute renal failure, serotonin syndrome, convulsion and coma. Management: Symptomatic and supportive treatment. Perform gastric lavage and administer activated charcoal as soon as possible to reduce absorption. Establish and maintain airway to ensure adequate oxygenation and respiratory function. Monitor cardiac function and vital signs.
Increased risk of bleeding tendencies with oral anticoagulants (e.g. warfarin), antiplatelet agents (e.g. ticlopidine, aspirin, dipyridamole), antipsychotics, and NSAIDs. Enhanced effect with concomitant use of other serotonergic agents (e.g. TCA, sumatriptan, tramadol, tryptophan, lithium, buspirone, fentanyl). Increased risk of lowering seizure threshold with other antidepressants (e.g. other SSRIs), neuroleptics (e.g. phenothiazines, thioxanthenes, butyrophenones), mefloquine, and bupropion. Increased serum concentration with CYP2C19 inhibitors (e.g. omeprazole, fluconazole, fluvoxamine) or cimetidine. Increases the plasma concentrations of CYP2D6 substrates (e.g. metoprolol, desipramine). Enhanced hypoglycaemic effect of antidiabetic agents. Potentially Fatal: Enhanced serotonergic effect with MAOIs (e.g. moclobemide, linezolid, IV methylene blue). Increased risk of QT interval prolongation with pimozide and other drugs prolonging QT interval including class IA and III antiarrhythmics, certain antibiotics (e.g. sparfloxacin, moxifloxacin, IV erythromycin, pentamidine), anti-malarial agents (e.g. halofantrine), and certain antihistamines (e.g. astemizole, mizolastine).
Increased risk of serotonin syndrome with St. John’s wort.
Description: Escitalopram, the S-enantiomer of the racemic citalopram, selectively inhibits the reuptake of serotonin thus potentiating serotonergic activity in the CNS. It has minimal effects on norepinephrine or dopamine reuptake. Onset: Antidepressant: Within a week. Pharmacokinetics: Absorption: Bioavailability: Approx 80%. Time to peak plasma concentration: Approx 5 hours. Distribution: Crosses the placenta and present in breastmilk. Volume of distribution: Approx 12-26 L/kg. Plasma protein binding: Approx 56%. Metabolism: Metabolised in the liver by CYP2C19 and CYP3A4 to S-desmethylcitalopram (S-DCT), and further metabolised by CYP2D6 to S-didesmethylcitalopram. Excretion: Via urine (8% as unchanged drug; 10% as S-DCT). Elimination half-life: Approx 27-32 hours.