Indications/Uses
Dosage/Direction for Use
Special Population: Geriatric (>65 years old): Initial Dose: Half the usual recommended dose.
Maximum Maintenance Dose: 10 mg daily.
Patients with Reduced Hepatic Function: Initial Dose: 5 mg daily for the first two weeks of treatment.
Depending on individual patient response, the dose may be increased to 10 mg daily.
Poor Metabolizers of CYP2C19: Initial Dose: 5 mg daily during the first two weeks of treatment.
Depending on individual patient response, the dose may be increased to 10 mg daily.
Or, as prescribed by a physician.
Overdosage
Symptoms such as dizziness, tremor, agitation to rare cases of serotonin syndrome, convulsion, coma, nausea/vomiting, hypotension, tachycardia, QT prolongation, arrhythmia, hypokalemia and hyponatremia have been reported.
There is no specific antidote to escitalopram overdose. It is important to establish and maintain airway to ensure adequate oxygenation and respiratory function. Gastric lavage and the use of activated charcoal should be considered. Gastric lavage should be carried out as soon as possible after oral ingestion. Cardiac and vital signs monitoring are recommended along with general symptomatic supportive measures. Due to escitalopram's large volume of distribution, forced diuresis, dialysis, hemoperfusion and exchange transfusion are unlikely to be of benefit.
In managing overdose, consider the possibility of multiple drug involvement.
Administration
Contraindications
Special Precautions
Suicidality and Antidepressant Drugs: Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of escitalopram or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond 24 years old; there was a reduction in risk with antidepressants compared to placebo in adults over 65 years and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Escitalopram is not approved for use in pediatric patients.
Clinical Worsening and Suicide Risk: Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment.
Symptoms such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is a concern that such symptoms may represent precursors to emerging suicidality.
Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, inpatients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression of suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.
If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms.
Prescriptions of escitalopram should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.
Screening Patients for Bipolar Disorder: Bipolar disorder may present initially as a major depressive episode. It is thought that treating such an episode with an antidepressant alone may precipitate a mixed/manic episode in patients at risk for bipolar disorder. Careful screening entails accurate recording of the patient's psychiatric history, especially family history of suicide, bipolar disorder and depression. Escitalopram is not approved for the treatment of bipolar depression.
Potential for Interaction with Monoamine Oxidase Inhibitors (MAOIs): There have been reports of serious, sometimes fatal, reactions including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma inpatients receiving serotonin reuptake inhibitor drugs in combination with a MAOI. These reactions have also been reported in patients who have recently discontinued SSRI treatment and have been started on an MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Limited animal data on the effects of combined use of SSRIs and MAOIs suggest that these drugs may act synergistically to elevate blood pressure and evoke behavioral excitation. Therefore, it is recommended that escitalopram should not be used in combination with a MAOI, or within 14 days of discontinuing treatment with a MAOI. Similarly, at least 14 days should be allowed after stopping escitalopram before starting a MAOI.
Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-like Reactions: There have been reports of potentially life-threatening serotonin syndrome or NMS-like reactions with selective norepinephrine reuptake inhibitors (SNRIs) and SSRIs alone, including escitalopram treatment but particularly with concomitant use of serotonergic drugs (including triptans) with drugs which impair serotonin metabolism (including MAOIs), or with antipsychotics or other dopamine antagonists. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucination, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberration (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Serotonin syndrome, in its most severe form can resemble NMS, which includes hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes. Patients should be monitored for the emergence of serotonin syndrome or NMS like signs and symptoms.
Discontinuation of Treatment: Discontinuation symptoms when stopping treatment are common, particularly if discontinuation is abrupt. The risk of discontinuation symptoms may be dependent on several factors such as the duration and dose of therapy and the rate of dose reduction. Dizziness, sensory disturbances (e.g., paresthesia and electric shock sensations), sleep disturbances (e.g., insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, sweating, headache, diarrhea, palpitations, emotional instability, irritability and visual disturbances are the most commonly reported reactions. Generally, these symptoms are mild to moderate; however, in some patients they may be severe in intensity. They usually occur within the first few days of discontinuing treatment but there have been very rare reports of such symptoms in patients who have inadvertently missed a dose. Generally, these symptoms are self-limiting and usually resolve within two weeks, though in some individuals they may be prolonged (two to three months or longer). It is therefore advised that escitalopram should be gradually tapered when discontinuing treatment over a period of several weeks or months, according to the patient's needs.
Abnormal bleeding: Cases of bleeding abnormalities of the skin and mucous membranes including purpura, ecchymoses, hematoma, epistaxis, vaginal bleeding and gastrointestinal bleeding were associated with the use of SSRIs.
Escitalopram should therefore be used with caution in patients concomitantly treated with oral anticoagulants, drugs known to affect platelet function (e.g., atypical antipsychotics and phenothiazines, most TCAs, acetylsalicylic acid and non-steroidal anti-inflammatory drugs, ticlopidine, and dipyridamole) as well as in patients with a past history of abnormal bleeding or those with predisposing conditions. Pharmacological gastroprotection should be considered for high risk patients.
Hyponatremia: Hyponatremia has been reported as a rare adverse reaction with the use of SSRIs probably due to inappropriate antidiuretic hormone secretion (SIADH). Caution should be exercised in patients at risk, such as the elderly, cirrhotic patients or patients concomitantly treated with drugs known to cause hyponatremia.
Activation of Mania/Hypomania: Clinical trials have documented an activation of mania/hypomania in patients treated with escitalopram. Escitalopram should be used cautiously in patients with a history of mania.
Interference with Cognitive and Motor Performance: Patients should be warned that psychoactive drugs may impair judgment, thinking or motor skills. They should be advised to avoid tasks which require complete mental alertness such as operating hazardous machinery and driving vehicles until they are sure that their treatment does not significantly impede their ability to perform such activities.
Diabetes: In patients with diabetes, treatment with an SSRI may alter glycemic control possibly due to improvement of depressive symptoms. Insulin and/or oral hypoglycemic dosage may need to be adjusted.
Use in Patients with Concomitant Illness: Clinical experience with escitalopram in patients with certain concomitant systematic illnesses is limited. Caution should be exercised when giving escitalopram in patients with diseases or conditions that produce altered metabolism or hemodynamic responses.
Escitalopram has not been systematically evaluated in patients with recent history of myocardial infarction or unstable heart disease.
Use in Children: Safety and effectiveness of escitalopram in pediatric patients have not been established.
Use in Elderly: Experience in those 65 years or older is insufficient to determine whether they respond differently from younger adults; increased sensitivity cannot be ruled out.
A reduced risk of suicidality was observed in adults 65 years or older with antidepressant therapy compared with placebo.
Use In Pregnancy & Lactation
Labor and Delivery: The effect of escitalopram on labor and delivery in humans is unknown.
Use in lactation: Escitalopram, like citalopram is excreted into human breast milk. Studies in breastfeeding mothers have shown that the mean combined dose of citalopram and demethylcitalopram transmitted to infants via breastmilk (expressed as a percentage of the weight-adjusted maternal dose) is 4.4 to 5.1%. Plasma concentrations of these drugs in infants were very low or absent and there were no adverse effects. While citalopram data support the safety of use of escitalopram in breastfeeding women the decision to breastfeed should always be made as an individual risk/benefit analysis.
Adverse Reactions
Cardiovascular: Palpitation, hypertension, postural hypotension, hypotension, bradycardia, tachycardia, abnormal electrocardiogram (ECG), ECG QT prolongation, flushing, hot flushes, chest pain, syncope, atrial fibrillation, cardiac failure, myocardial infarction, torsade de pointes, ventricular arrhythmia, ventricular tachycardia, varicose vein, deep vein thrombosis, thrombosis, phlebitis.
Nervous system: Dizziness, vertigo, insomnia, somnolence, headache, migraine, paresthesia, yawning, light-headed feeling, tremor, restless legs, shaking, twitching, dysequilibrium, tics, carpal tunnel syndrome, involuntary muscle contractions, sluggishness, abnormal coordination, faintness, hyperreflexia, increased muscular tone, extrapyramidal disorders, movement disorder, lethargy, irritability, impaired concentration, jitteriness, panic reaction, agitation, apathy, forgetfulness, amnesia, depression, aggravated depression, nervousness, tremulousness nervous, aggravated restlessness, anxiety attack, bruxism, confusion, depersonalization, disorientation, emotional lability, feeling unreal, abnormal crying, excitability, auditory hallucination, visual hallucination, suicidal tendency, suicide attempt, serotonin syndrome, dyskinesia, tardive dyskinesia, convulsions, seizures, akathisia, dysarthria, dystonia, hypoesthesia, myoclonus, nystagmus, abnormal gait, acute psychosis, aggression, anger, delirium, delusion, nightmare, abnormal dreaming, paranoia.
Gastrointestinal: Dry mouth, nausea, diarrhea, constipation, indigestion, abdominal pain, vomiting, flatulence, heartburn, abdominal cramps, gastroenteritis, gastroesophageal reflux, bloating, abdominal discomfort, dyspepsia. Increased stool frequency, belching, gastritis, hemorrhoids, gagging, gastric polyposis, difficult swallowing, gastrointestinal hemorrhage, pancreatitis, rectal hemorrhage.
Hematologic: Bruise, anemia, nosebleed, hematoma, hemolytic anemia, leukopenia, thrombocytopenia, international normalized ratio (INR) increased, prothrombin decreased.
Endocrine/Metabolic/Nutritional: Increased weight, decreased weight, decreased appetite, increased appetite, carbohydrate craving, hyperglycemia, hypoglycemia, thirst, increased bilirubin, gout, hypercholesterolemia, hyperprolactinemia, hypokalemia, inappropriate ADH secretion, syndrome of inappropriate antidiuretic hormone (SIADH), ejaculation disorder, impotence, priapism, decreased libido, anorgasmia.
Musculoskeletal: Neck/shoulder pain, leg pain, arthralgia, myalgia, jaw stiffness, muscle cramps, muscle stiffness, arthritis, muscle weakness, back discomfort, arthropathy, jaw pain, joint stiffness, rhabdomyolysis.
Respiratory: Rhinitis, sinusitis, bronchitis, sinus congestion, coughing, nasal congestion, sinus headache, asthma, shortness of breath, laryngitis, pneumonia, tracheitis, epistaxis, tightness of chest, pulmonary embolism.
Hepatic: Abnormal liver function, hepatitis, fulminant hepatitis, hepatic failure, hepatic necrosis, hepatic enzymes increased.
Skin and appendages: Increased sweating, rash, pruritus, acne, alopecia, eczema, dermatitis, dry skin, folliculitis, lipoma, furunculosis, dry lips, skin nodule, ecchymosis, angioedema, urticaria, erythema multiforme, photosensitivity reaction, Stevens-Johnson Syndrome, toxic epidermal necrolysis.
Special senses: Blurred vision, conjunctivitis, vision abnormal, dry eyes, eye irritation, visual disturbance, eye infection, mydriasis, diplopia, glaucoma, choreoathelosis, earache, tinnitus, taste alteration, taste disturbance, metallic taste.
Urogenital/Reproductive: Menstrual disorder, menstrual cramps, menorrhagia, metrorrhagia, breast neoplasm, pelvic inflammation, premenstrual syndrome, spotting between menses, urinary frequency, urinary tract infection, urinary urgency, kidney stone, dysuria, blood in urine, glactorrhea, acute renal failure.
Other: Spontaneous abortion.
Drug Interactions
Other Interaction: Electroconvulsive Therapy (ECT): There are no clinical studies on the combined use of ECT and escitalopram therefore, caution is advised.
Storage
Action
Escitalopram has a primary high-affinity binding site and a secondary lower-affinity allosteric site in the serotonin transporter protein. Binding of escitalopram to the allosteric site enhances binding of the drug to the primary binding site, resulting in more complete serotonin reuptake inhibition. This also explains the enhanced potency of escitalopram compared with citalopram.
In vitro studies showed that escitalopram had no, or minimal effect on noradrenaline (NA), dopamine (DA) and gamma-amino butyric acid (GABA) uptake.
Compared with many tricyclic antidepressants (TCAs) and some of the selective serotonin reuptake inhibitors (SSRIs), escitalopram has no or very low affinity for a number of receptors such as 5-HT1A, 5-HT2, DA D1 and DA D2 receptors, α1-, α2-, β-adrenoceptors, histamine H1, muscarine cholinergic, benzodiazepine and opioid receptors.
Pharmacokinetics: Escitalopram's absorption is almost complete and independent of food intake. As with racemic citalopram, the absolute bioavailability of escitalopram is about 80%.
After multiple dosing, mean time to maximum concentration (mean Tmax) is about four hours. Escitalopram exhibits linear pharmacokinetics. Steady-state plasma levels are achieved in about one week.
Escitalopram is widely distributed throughout tissues, with an apparent volume of distribution after oral administration of 1,100 L. It exhibits low protein-binding (average 56%) over a wide range of concentrations, indicating a low potential for drug displacement interactions.
Escitalopram is metabolized in the liver to less lipophilic compounds that are readily excreted in urine. Biotransformation of the drug occurs via oxidative metabolism with N-demethylation to S-demethylcitalopram (S-DCT) and S-didemethylcitalopram (S-DDCT), deamination and dehydrogenation to a propionic acid derivative, and also N-oxidation and glucuronide conjugation. N-demethylation of escitalopram to S-DCT is mediated by three hepatic CYP isoenzymes in parallel, CYP3A4, CYP2C19 and, to a lesser extent, CYP2D6. After multiple dose administration of citalopram, poor metabolizers of CYP2C19 had higher plasma concentrations of escitalopram and lower concentrations of S-DCT than extensive metabolizers; however, the urinary recovery and renal clearance of escitalopram and its metabolites did not differ significantly between the two phenotypes. The metabolites of escitalopram are unlikely to contribute to the clinical effects, since they are present at much lower concentrations in vivo and have been shown in vitro to be much weaker inhibitors of serotonin reuptake.
Escitalopram's elimination half-life (t½) is about 30 hrs. Oral plasma clearance is 0.6 L/min. Escitalopram and its metabolites are eliminated by both hepatic and renal routes, with major part of the dose excreted as metabolites in the urine.
Special Population: Hepatic Impairment: In patients with mild to moderate hepatic impairment (Child-Pugh Criteria A and B), the t½ of escitalopram was about twice as long and the exposure was about 60% higher than in subjects with normal liver function. The dose of escitalopram should therefore be reduced in such patients.
Renal Impairment: The pharmacokinetics of escitalopram in patients with renal impairment have not been explicitly investigated. However, in patients with mild to moderate renal impairment (creatinine clearance 10 to 53 mL/min), the t½ of a single dose of citalopram was increased by approximately 35%, with oral and renal clearance being about 15% and 40% lower, respectively, than in healthy volunteers. Plasma concentrations of the metabolites have not been studied, but it may be elevated.
Geriatrics: Escitalopram AUC and half-life were increased by approximately 50% in the elderly (>65 years); Cmax was unchanged. A lower initial dosage should be considered.
MedsGo Class
Features
- Esomeprazole