Escitalopram

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Escitalopram quick reference

Escitalopram
Escitalopram general drug information
 Pronunciation (es sye TAL oh pram) (.wav file)
 Trade Name(s) Lexapro
 How Supplied Tablets: 5 mg, 10 mg, 20 mg
Oral solution: 5 mg/5 mL
 Generic Availability No generics available
 Patent Expiry Date March 14, 2012
 Classification Selective serotonin reuptake inhibitor (SSRI)
 Schedule Rx
 Pregnancy Category C
 Breast-feeding Concentrations of citalopram have been found in breast milk. Caution should be used.
Escitalopram chemical information
 IUPAC Name S-(+)-1-[3-(dimethylamino)propyl]-1-(p-fluorophenyl)-5-phthalancarbonitrileoxalate
 Empirical Formula (C20H21FN2O)•C2H2O4
 Molecular Weight 414.4 g/mol
pharmacokinetic information  |  pharmacogenomic information

Description

Escitalopram belongs to a class of medications known as the selective serotonin reuptake inhibitors (SSRIs). SSRIs inhibit the reuptake of serotonin (5-HT), which is thought to be responsible for mood regulation. Escitalopram is the S-enantiomer of citalopram which is responsible for virtually all of the antidepressant effects of escitalopram by the inhibition of serotonin reuptake effect.[1] It was approved by the U.S. FDA for the treatment of Major Depressive Disorder and Generalized Anxiety Disorder.[1]

On October 15, 2004, the FDA mandated the inclusion of a black box warning in the package inserts of all antidepressants outlining the potential for increased suicidal ideations and behavior in children and adolescents who use these medications. A Patient Medication Guide(MedGuide) concerning this risk is also required to be dispensed with each filling of an antidepressant medication. The regulations have been created due to recent findings in the literature.[2]

Mechanism of Action

Escitalopram, the S-enantiomer of citalopram, is a highly selective serotonin reuptake inhibitor. It has minimal effects on norepinephrine and dopamine neuronal reuptake. Escitalopram is at least 100-fold more potent than the R-enantiomer when comparing the inhibition of 5-HT reuptake and inhibition of 5-HT neuronal firing rate.[3] SSRIs exert their actions by inhibiting the CNS presynaptic neuronal reuptake of serotonin. This increases the concentration of serotonin in the synaptic cleft and the potential of serotonergic binding at postsynaptic receptors. SSRIs have side effect profiles that are generally considered favorable compared to other classes due to their lack of anticholinergic activity and their lack of monoamine oxidase inhibition.[4]

Escitalopram has minimal affinity for serotonergic (5-HT1-7) or other receptors including alpha- and beta-adrenergic, dopamine (D1-5), histamine (H1-3), muscarinic (M1-5), and benzodiazepine receptors. Antagonism of muscarinic, histaminergic and adrenergic receptors is suggested to be associated with various anticholinergic, sedative and cardiovascular side effects seen in other psychotropic drugs.[1]

Time Required for Therapeutic Response

  • Initial: within 1 week[1]
  • Maximum: within 4 weeks[1]

Pharmacokinetics

Absorption
A therapeutically administered dose of escitalopram produces a peak concentration after approximately 5 hours. The absolute bioavailability of escitalopram is unknown, but that of citalopram is 80%. Coadministration with food does not affect the bioavailability of escitalopram.[1]

Distribution
Approximately 56% of the circulating drug is bounded to plasma proteins.[1] The escitalopram plasma steady state is achieved within 10 days. The apparent volume of distribution is approximately 20 L/kg.[5]

Metabolism
The primary proposed mechanism of escitalopram metabolism is through cytochrome P450 3A4 and 2C19 N-demethylation.[1] Escitalopram is metabolized to S-demethylcitalopram (S-DCT) and S-didemethylcitalopram (S-DDCT). Unchanged escitalopram is the predominant compound in plasma.

Excretion
Less than 7% of escitalopram recovered in the urine. The mean half-life (t1/2) of escitalopram is approximately 27-32 hours.[1]

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Special Population Pharmacokinetics

  • Renal insufficiency: No dosage adjustment is necessary for patients with mild to moderate renal insufficiency. For patients with severely reduced renal function (creatinine clearance <20 mL/min), no information regarding the pharmacokinetic of escitaopram is available.[1]
  • Hepatic insufficiency: The recommended dose of escitalopram for hepatically impaired patients is 10 mg/day.[1]
  • Hemodialysis: Data not available.[1]
  • Geriatric: The AUC and half-life of escitalopram were increased by approximately 50% in elderly patients (>65 years old). The recommended dose for elderly patients is 10 mg.[1]
  • Pediatric: Data not available.[1]
  • Gender: No dosage adjustment is necessary.[1]

Indications and Dosages

FDA Approved Indications

Major Depressive Disorder[1]

  • Starting dose:
    • 10 mg once daily
  • Maintenance dose:
    • Recommended maximum maintenance dose is 20 mg once daily.
    • No greater benefit of 20 mg over 10 mg was found.
  • Titration schedule: The dose can be increased to 20 mg but this should occur after a minimum of one week.

Generalized Anxiety Disorder[1]

  • Starting dose:
    • 10 mg once daily
  • Maintenance dose:
    • Recommended maximum maintenance dose is 20 mg once daily.
    • No greater benefit of 20 mg over 10 mg was found.
  • Titration schedule: The dose can be increased to 20 mg but this should occur after a minimum of one week.

Discontinuation of treatment: A gradual reduction in the dose is recommended whenever possible.[1]
Switching patients to or from a monoamine oxidase inhibitor: A 14 day period between discontinuation of an MAOI and initiation of escitalopram therapy is required.[1]

Non-FDA Approved Indications

  • Panic Disorder[6]
  • Social Phobia (social anxiety disorder)[7][8]

Dosage Adjustment

Hepatic insufficiency: Initiate and maintain therapy with 10 mg once daily in patients with hepatic impairment.[1]
Hemodialysis: Unknown.
Geriatric: A lower maximum daily dose is recommended for depression (see Dosage Limits).

Dosage Limits

  • Adults: 20 mg/day
  • Elderly: 10 mg/day for depression, 20 mg/day for anxiety
  • Adolescents and children: Unknown; safety and efficacy has not been established in this population


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Administration

  • Route: Oral[1]
  • Method:
    • Swallow tablet or solution with a full (8 oz) glass of water.
    • The drug should be taken once daily at any time during the day (the time should be consistent from day to day) and may be taken without regard to meals.[1]

Monitoring Parameters

  • LFTs (baseline)
  • Thyroid function tests
  • Mental status for depression.[1]
  • Suicidal ideation (especially at the beginning of therapy or when doses are increased or decreased)
  • Anxiety
  • Social functioning
  • Mania
  • Panic attacks
  • Akathisia

Contraindications/Precautions

Contraindications

  • Concomitant use in patients taking monoamine oxidase inhibitors (MAOIs) (a 14-day period between discontinuation of an MAOI and initiation of escitalopram therapy is required)[1]

Precautions

  • Abrupt discontinuation of treatment is not advised (reports of spontaneous adverse events occurring upon discontinuation including the following: dysphoric mood, irritability, agitation, dizziness, sensory disturbances, anxiety, confusion, headache, lethargy, emotional lability, insomnia, and hypomania)[1]
  • Abnormal bleeding (studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding, and concurrent use of a nonsteroidal anti-inflammatory drug (NSAID) or aspirin potentiated the risk of bleeding)[1][9]
  • Hyponatremia[10]
  • Bipolar disorder (activation of mania/hypomania)
  • Seizures (in clinical trials, cases of convulsion have been reported - escitalopram should be introduced with care in patients with a history of seizure disorder)
  • Suicidal ideations
  • Interference with cognitive and motor performance
  • Use in patients with diseases or conditions that produce altered metabolism or hemodynamic responses

Pregnancy indications

Category C [1]

Animal reproduction studies using escitalopram in pregnancy resulted in adverse effects on the fetus including slightly increased offspring mortality and growth retardation. Escitalopram may be used during pregnancy if the potential benefits justify the potential risks to the fetus.[1]

Breast-feeding indications

No available data for escitalopram. Racemic citalopram is secreted into human milk. Escitalopram may be used in nursing mothers if the potential benefits of the mother justify the potential risks to the infant.[1]

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Drug-Drug, -Food, -Herb Interactions

Click the link above to go to the drug interactions page.

Adverse Reactions/Side Effects

Escitalopram is generally well tolerated with a low discontinuation rate (<2%) in clinical trials involving 2502 patients. The most common adverse reactions experienced in clinical trials were constipation, flatulence, dyspepsia, and abdominal pain.[11]

Escitalopram Adverse Reactions Chart
Incidence Body System Adverse Reactions
>10% All Headache (24%), somnolence (6% to 13%), insomnia (9% to 12%)
1-10% CNS Dizziness (5%), fatigue (5% to 8%), abnormal dreaming, blurred vision, concentration impairment, fever, irritability, lethargy, lightheadedness, migraine, vertigo, yawning
Cardiovascular Chest pain, flushing, hypertension, palpitations
Dermatologic Rash
GI Diarrhea (8%), xerostomia (6% to 9%), appetite decreased (3%), constipation (3% to 5%), indigestion (3%), abdominal pain (2%), abdominal cramps, increased appetite, flatulence, gastroenteritis, gastroesophageal reflux, heartburn, toothache, vomiting, weight gain/loss
Genitourinary Impotence (3%)[12], libido decrease (3% to 7%), anorgasmia (2% to 6%), menstrual cramps, menstrual disorder, urinary frequency increased, urinary tract infection
Neuromuscular/skeletal Arthralgia, limb pain, muscle cramp, myalgia, neck/shoulder pain, paresthesia, tremor
Respiratory Rhinitis (5%), sinusitis (3%), bronchitis, cough, nasal or sinus congestion, sinus headache
Miscellaneous Diaphoresis (4% to 5%), flu-like syndrome (5%), allergy, earache, tinnitus
<1% All Abdominal discomfort, abnormal crying, acne, agitation, alopecia, amnesia, anaphylaxis, anemia, anxiety attack, apathy, arthritis, arthropathy, asthma, auditory hallucination, back discomfort, belching, bilirubin increased, bloating, bradycardia, bruise, bruxism, carbohydrate craving, carpal tunnel syndrome, chest tightness, chills, confusion, conjunctivitis, depersonalization, depression, dermatitis, dry eyes, dry skin, dysequilibrium, dyspepsia, dysuria, ECG abnormal, eczema, edema, emotional lability, excitability, eye infection, eye irritation, faintness, feeling unreal, folliculitis, forgetfulness, furunculosis, gagging, gastritis, gout, hematoma, hemorrhoids, hypercholesterolemia, hyperglycemia, hyper-reflexia, jaw pain, jaw stiffness, jitteriness, joint stiffness, kidney stone, laryngitis, leg pain, lipoma, malaise, menorrhagia, muscle contractions (involuntary), muscle stiffness, muscle weakness, muscular tone increased, nervousness, nosebleed, panic reaction, pelvic inflammation, pneumonia, pruritus, pupils dilated, restless legs, restlessness aggravated, shaking, shortness of breath, spotting between menses, stool frequency increased, suicidal tendency, suicide attempt, syncope, tachycardia, taste alteration, tics, tracheitis, tremulousness nervous, twitching, varicose vein, vision abnormal, visual disturbance, weakness.

Postmarketing and/or case reports: Acute renal failure, aggression, akathisia, allergic reaction, angioedema, atrial fibrillation, choreoathetosis, delirium, dyskinesia, ecchymosis, epidermal necrolysis, erythema multiforme, grand mal seizure, hallucination, hemolytic anemia, hepatic necrosis, hepatitis, nystagmus, pancreatitis, priapism, prolactinemia, prothrombin decreased, pulmonary embolism, QT prolonged, rhabdomyolysis, serotonin syndrome, SIADH, spontaneous abortion, thrombocytopenia, thrombosis, torsade de pointes, ventricular arrhythmia, withdrawal syndrome

Overdosage Measures

Treatment of escitalopram overdose is generally guided by symptoms and supportive treatment should be initiated as necessary.[1]

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Product Information and Distribution

Note: appearance only available for brand-name product
Dose/form Drug color(s) Drug shape Markings or odor/flavor
5 mg tablet white round FL/5
10 mg tablet white round FL/10
20 mg tablet white round FL/20
5 mg/5 mL solution clear - peppermint flavor
  • Inactive ingredients for tablets: cellulose, colloidal silicon dioxide, croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, talc, titanium dioxide.
  • Inactive ingredients for solution: citric acid, glycerin, malic acid, methylparaben, natural peppermint flavor, propylene glycol, propylparaben, purified water, sodium citrate, sorbitol

Patient Information

  • Take as directed. Do not discontinue abruptly.
  • Take in the morning to prevent insomnia.
  • Avoid OTC medications and alcohol unless instructed by your physician.
  • May cause dizziness, drowsiness, or lightheadedness. Use caution when driving or operating heavy machinery.
  • May cause nausea, vomiting, dry mouth, or anorexia. Eat smaller meals and use lozenges or chewing gum to prevent these problems.
  • May cause menstrual cramps, muscle pain or cramps. Talk to your doctor before using any OTC pain medications.
  • May cause male sexual dysfunction. This condition is reversible. Talk to your doctor if these symptoms become bothersome.
  • Report increased depression, confusion, impaired concentration, severe headache, insomnia, nightmares, irritability, acute anxiety, panic attacks, thoughts of suicide, persistent GI changes, chest pain or palpitations, blurred vision or vision changes, ringing in ears, unusual cough or worsening of your condition.
  • Inform your doctor if you are or intend to become pregnant. Breast feeding is not recommended.
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References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 1.24 1.25 1.26 1.27 1.28 1.29 Lexapro® (escitalopram oxalate) package insert. St. Louis, MO; Forest Laboratories; 2003 Dec.
  2. ↑ Tiihonen J, Lonnqvist J, Wahlbeck K, Klaukka T, Tanskanen A, Haukka J. Antidepressants and the risk of suicide, attempted suicide, and overall mortality in a nationwide cohort. Archives of general psychiatry. 2006 Dec;63(12):1358-67.
  3. ↑ Role of selective serotonin reuptake inhibitors in psychiatric disorders: a comprehensive review. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 27(1):85-102, 2003 Feb.
  4. ↑ Dipiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 5th Edition ed. New York, NY: The McGraw-Hill Companies, Inc 2002.
  5. ↑ Sogaard B, Mengel H, Rao N, Larsen F.The pharmacokinetics of escitalopram after oral and intravenous administration of single and multiple doses to healthy subjects.J Clin Pharmacol. 2005 Dec;45(12):1400-6.
  6. ↑ Stahl SM, Gergel I, Li D. Escitalopram in the treatment of panic disorder: a randomized, double-blind, placebo-controlled trial.J Clin Psychiatry. 2003 Nov;64(11):1322-7.
  7. ↑ Montgomery SA, Nil R, Durr-Pal N, Loft H, Boulenger JP. A 24-week randomized, double-blind, placebo-controlled study of escitalopram for the prevention of generalized social anxiety disorder.J Clin Psychiatry. 2005 Oct;66(10):1270-8.
  8. ↑ Kasper S, Stein DJ, Loft H, Nil R. Escitalopram in the treatment of social anxiety disorder: randomised, placebo-controlled, flexible-dosage study.Br J Psychiatry. 2005 Mar;186:222-6.
  9. ↑ Dalton, SO, Johansen C, Mellemkjaer L, et al. Use of selective serotonin reuptake inhibitors and the risk of upper gastrointestinal tract bleeding: a population-based cohort study. Arch Intern Med 2003;163:59—64.
  10. ↑ Miehle K, Paschke R, Koch CA.Citalopram therapy as a risk factor for symptomatic hyponatremia caused by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH): a case report.Pharmacopsychiatry. 2005 Jul;38(4):181-2.
  11. ↑ Lexi-Comp (2003). Drug Information Handbook. 11th Edition., APhA.
  12. ↑ Clayton AH. Croft HA. Horrigan JP. Wightman DS. Krishen A. Richard NE. Modell JG. Bupropion extended release compared with escitalopram: effects on sexual functioning and antidepressant efficacy in 2 randomized, double-blind, placebo-controlled studies. [Comparative Study. Meta-Analysis. Randomized Controlled Trial. Research Support, Non-U.S. Gov't] Journal of Clinical Psychiatry. 67(5):736-46, 2006 May.

PUBMED References

Efficacy Trial Articles

  1. Baldwin DS, Cooper JA, Huusom AK, Hindmarch I.A double-blind, randomized, parallel-group, flexible-dose study to evaluate the tolerability, efficacy and effects of treatment discontinuation with escitalopram and paroxetine in patients with major depressive disorder.Int Clin Psychopharmacol. 2006 May;21(3):159-69.
  2. Burke WJ, Gergel I, Bose A. Fixed-dose trial of the single isomer SSRI escitalopram in depressed outpatients. J Clin Psychiatry 2002;63:331–6..
  3. Davidson JR, Bose A, Korotzer A, Zheng H.Escitalopram in the treatment of generalized anxiety disorder: double-blind, placebo controlled, flexible-dose study.J Depress Anxiety. 2004;19(4):234-40.
  4. Fineberg NA, Tonnoir B, Lemming O, Stein DJ.Escitalopram prevents relapse of obsessive-compulsive disorder.Eur Neuropsychopharmacol. 2007 Jan 18.
  5. Kasper S, Stein DJ, Loft H, Nil R.Escitalopram in the treatment of social anxiety disorder: randomised, placebo-controlled, flexible-dosage study.Br J Psychiatry. 2005 Mar;186:222-6.
  6. Kornstein SG, Bose A, Li D, Saikali KG, Gandhi C.Escitalopram maintenance treatment for prevention of recurrent depression: a randomized, placebo-controlled trial.J Clin Psychiatry. 2006 Nov;67(11):1767-75.
  7. Lam RW, Andersen HF.The influence of baseline severity on efficacy of escitalopram and citalopram in the treatment of major depressive disorder: an extended analysis.Pharmacopsychiatry. 2006 Sep;39(5):180-4.
  8. Mao PX, Tang YL, Jiang F, Shu L, Gu X, Li M, Qian M, Ma C, Mitchell PB, Cai ZJ.Escitalopram in major depressive disorder: a multicenter, randomized, double-blind, fixed-dose, parallel trial in a Chinese population.Depress Anxiety. 2006 Dec 5.
  9. Mohamed S, Osatuke K, Aslam M, Kasckow J. Escitalopram for comorbid depression and anxiety in elderly patients: A 12-week, open-label, flexible-dose, pilot trial.Am J Geriatr Pharmacother. 2006 Sep;4(3):201-9.
  10. Montgomery SA, Loft H, S´anchez C, Reines EH, Papp M.Escitalopram (S-enantiomer of citalopram): clinical efficacy and onset of action predicted from a rat model. Pharmacol Toxicol 2001;88:282–6.
  11. Olie JP, Tonnoir B, Menard F, Galinowski A. A prospective study of escitalopram in the treatment of major depressive episodes in the presence or absence of anxiety.Depress Anxiety. 2006 Oct 13.
  12. Wade A, Lemming OM, HedegaardKB. Escitalopram 10 mg/day is effective and well tolerated in a placebo-controlled study in depression in primary care. Int Clin Psychopharmacol 2002;17:95–102.
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Therapeutic Class Comparison Articles

  1. Baldwin DS, Cooper JA, Huusom AK, Hindmarch I.A double-blind, randomized, parallel-group, flexible-dose study to evaluate the tolerability, efficacy and effects of treatment discontinuation with escitalopram and paroxetine in patients with major depressive disorder.Int Clin Psychopharmacol. 2006 May;21(3):159-69.
  2. Baldwin DS, Huusom AK, Maehlum E.Escitalopram and paroxetine in the treatment of generalised anxiety disorder: randomised, placebo-controlled, double-blind study.Br J Psychiatry. 2006 Sep;189:264-72.
  3. Boulenger JP, Huusom AK, Florea I, Baekdal T, Sarchiapone M.A comparative study of the efficacy of long-term treatment with escitalopram and paroxetine in severely depressed patients.Curr Med Res Opin. 2006 Jul;22(7):1331-41.
  4. Kennedy SH, Andersen HF, Lam RW.Efficacy of escitalopram in the treatment of major depressive disorder compared with conventional selective serotonin reuptake inhibitors and venlafaxine XR: a meta-analysis.J Psychiatry Neurosci. 2006 Mar;31(2):122-31. Erratum in: J Psychiatry Neurosci. 2006 Jul;31(4):228.
  5. Moore N, Verdoux H, Fantino B.Prospective, multicentre, randomized, double-blind study of the efficacy of escitalopram versus citalopram in outpatient treatment of major depressive disorder.Int Clin Psychopharmacol. 2005 May;20(3):131-7.

Pharmacokinetics Articles

  1. Areberg J, Christophersen JS, Poulsen MN, Larsen F, Molz KH.The pharmacokinetics of escitalopram in patients with hepatic impairment.AAPS J. 2006 Jan 20;8(1):E14-9
  2. Preskorn SH, Greenblatt DJ, Flockhart D, Luo Y, Perloff ES, Harmatz JS, Baker B, Klick-Davis A, Desta Z, Burt T.Comparison of Duloxetine, Escitalopram, and Sertraline Effects on Cytochrome P450 2D6 Function in Healthy Volunteers.J Clin Psychopharmacol. 2007 Feb;27(1):28-34.
  3. Sogaard B, Mengel H, Rao N, Larsen F.The pharmacokinetics of escitalopram after oral and intravenous administration of single and multiple doses to healthy subjects.J Clin Pharmacol. 2005 Dec;45(12):1400-6.
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Drug Interaction Articles

  1. Gutierrez MM, Rosenberg J, Abramowitz W.An evaluation of the potential for pharmacokinetic interaction between escitalopram and the cytochrome P450 3A4 inhibitor ritonavir.Clin Ther. 2003 Apr;25(4):1200-10.
  2. Malling D, Poulsen MN, Sogaard B.The effect of cimetidine or omeprazole on the pharmacokinetics of escitalopram in healthy subjects.Br J Clin Pharmacol. 2005 Sep;60(3):287-90.

Adverse Effects Articles

  1. Clayton AH. Croft HA. Horrigan JP. Wightman DS. Krishen A. Richard NE. Modell JG. Bupropion extended release compared with escitalopram: effects on sexual functioning and antidepressant efficacy in 2 randomized, double-blind, placebo-controlled studies.(Comparative Study. Meta-Analysis. Randomized Controlled Trial. Research Support, Non-U.S. Gov't)Journal of Clinical Psychiatry.67(5):736-46, 2006 May.
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Compliance Articles

Pharmacoeconomic Articles

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External Links

Clinical treatment guidelines

Patient information pages

Other resources

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