Escitalopram

Earn CME/CE in your profession:


Continuing Education Activity

Escitalopram is a medication used in the management and treatment of major depressive disorder and generalized anxiety disorder. It is in the selective serotonin reuptake inhibitor class of drugs. This activity will highlight the mechanism of action, adverse event profile, and other key factors (e.g., off-label uses, dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions, adverse events) pertinent for members of the healthcare team in the management of patients with depression, anxiety, and other related conditions.

Objectives:

  • Identify the mechanism of action of escitalopram.
  • Describe the potential adverse effects of escitalopram.
  • Review the appropriate monitoring for therapy with escitalopram.
  • Summarize interprofessional team strategies for improving care coordination and communication when initiating escitalopram to improve patient outcomes.

Indications

Escitalopram, a selective serotonin reuptake inhibitor (SSRI) and the S-enantiomer of racemic citalopram, is known to be the most selective of SSRIs. SSRIs are widely known for their use in the treatment of depression, anxiety, and other related disorders.[1] Escitalopram (and SSRIs) are also known for their off-label use for the treatment of social anxiety disorder, obsessive-compulsive disorder, panic disorder, posttraumatic stress disorder, premenstrual dysphoric disorder, and vasomotor symptoms of menopause.[2][3][4][5]

Mechanism of Action

SSRI's mechanism of action is exerted by binding to the sodium-dependant serotonin transporter protein (SERT), also known as 5-HTT, which is located in the presynaptic neuron. SERT works by re-uptaking serotonin from the synaptic cleft back to the presynaptic neuron. As SSRIs bind to SERT they inhibit the re-uptake of serotonin and thus increase the amount of serotonin in the synaptic cleft. [6] This activity potentiates the effect of serotonin in the central nervous system. Serotonin or 5-hydroxytryptamine (5-HT) modulates a wide range of human behavioral processes which include mood, perception, memory, anger, aggression, fear, stress response, appetite, addiction, and sexuality. For these to happen, brain regions like cortical, limbic, midbrain, and hindbrain regions express multiple serotonin receptors. [7] There are 5 main serotonin receptors; 5-HT1A, 5-HT1B, 5-HT4, 5-HT6, 5-HT7 located in the brain. [8] In total there are 15 known serotonin receptors, and all of them can also be found outside the central nervous system. [7]

Administration

Escitalopram is administered via the oral route (OR). It is available as a 1 mg/mL oral solution as well as 5 mg, 10 mg, or 20 mg tablets. It is taken once daily, either with or without food. The typical starting dose for escitalopram is 10 mg, and after one week, the dose can be increased to achieve proper symptoms control.[9] A 4-week dose reduction is recommended when trying to switch escitalopram for another SSRI. The half-life of escitalopram is 27 to 32 hours (1.5 days), and it takes 7 to 10 days for it to reach a steady-state in the blood. [10] 

Adverse Effects

Escitalopram and SSRIs have a lower toxicity profile than older antidepressants. Despite this, they have been associated with significant adverse effects. [11]The most commonly observed adverse effects reported are; insomnia, sexual dysfunction (primarily decreased libido, anorgasmia, and male ejaculatory delay), nausea, increased sweating, fatigue, and somnolence. [12] Escitalopram can potentially cause withdrawal symptoms like dizziness, nausea, lethargy, and dizziness if abruptly stopped.  [10]

Escitalopram can cause SSRI-induced syndrome of inappropriate antidiuretic hormone secretion (SSRI-induced SIADH) leading to hyponatremia, especially in the elderly population.[13] Depending on the severity of hyponatremia, symptoms can range from anorexia, nausea, vomiting, fatigue, headache, to more severe conditions like; altered mental status, seizures, and even coma. [14][13]

QT prolongation and serotonin syndrome are amongst the rare but serious adverse effects caused by Escitalopram. QT prolongation is defined as a corrected QT interval on an EKG of greater than 500 ms or an increase from a baseline interval of more than 60 ms.[15] QT prolongation can cause potentially fatal cardiac arrhythmias, including torsade de pointes.[16] The mechanism by which escitalopram causes QT prolongation is a poorly understood phenomenon.[15] However, it is known to be a dose-dependent relationship.[17] 

Serotonin syndrome, a potentially life-threatening side effect results from an excess amount of serotonin in the peripheral and central nervous systems. This medical condition can lead to symptoms of neuromuscular excitation and autonomic stimulation. Serotonin syndrome is more likely to occur in patients taking high-dose SSRIs, who have overdosed, or patients taking more than one serotonergic drug, especially if they work by different mechanisms (an SSRI plus a monoamine oxidase inhibitor, for example). [18] Symptoms of serotonin syndrome may include autonomic instability such as tachycardia, hypertension, dizziness, diaphoresis, flushing, mydriasis, and increased temperature (above 38 degrees celsius). It can also include nausea, vomiting, diarrhea, and mental status changes like agitation, delirium, hallucinations, somnolence, and coma. Neuromuscular symptoms can also present, including incoordination, rigidity, clonus, hyperreflexia, tremors, and hypertonicity. [18] There are reports of severe cases presenting with EKG changes and seizures.[19] [18] A 4 weeks weaning off period before trying another antidepressant therapy is advised to avoid causing serotonin syndrome. [20]

Contraindications

In order to prescribe escitalopram, a proper risk assessment for hypersensitivity reactions to other medications (especially antidepressants and SSRIs), possible QT prolongation, and serotonin syndrome is indicated for all patients.  If the patient has a history of hypersensitivity reactions to escitalopram or citalopram this is considered an absolute contraindication.[11]

Co-administration of a monoamine oxidase inhibitor (MAOI) is also contraindicated with escitalopram due to the risk of causing serotonin syndrome. MAOIs include phenelzine, selegiline, isocarboxazid, and selegiline. [21] Other medications contraindicated due to the possibility of inducing serotonin syndrome include; antidepressants, triptans, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, St. John's Wort. Drugs that impair the metabolism of serotonin, such as intravenous methylene blue, linezolid, MAOIs, and other psychiatric medications are also contraindicated. [18]

Although it is a relative contraindication, the risk of QT prolongation is another consideration when starting escitalopram. A family history of long QT syndrome, or sudden, premature cardiac death, should be evaluated. Concomitant use of other drugs that can cause prolonged QT syndrome, including antipsychotics (especially older typical antipsychotics) should also be carefully assessed. [16]

In recent years, liver enzyme CYP2C19 activity has been evaluated in pharmacogenetics as a determinant in contraindicating escitalopram use. CYP2C19 metabolizes escitalopram, and it is now possible to evaluate an individual patient's activity of this enzyme via genetic testing. Poor metabolizers, or those with decreased activity of this enzyme, are shown to have higher concentrations of escitalopram in their bloodstream and are therefore at higher risk of adverse drug reactions.[17] If a patient's CYP2C19 status is known and is weak, it is reasonable to evaluate whether escitalopram use is necessary or whether adjustments should be made to the dose to avoid serious adverse drug reactions.[22] 

Monitoring

Patients taking escitalopram should be monitored for mood or behavioral changes, including suicidality. An increase in suicidal thoughts and self-destructive behavior in pediatric and adolescent patients taking SSRIs have been documented in the past. [1] Electrolyte disturbances (SSRI-induced SIADH), EKG changes (QT prolongation), should also be assessed in subsequent visits with a basic metabolic panel and EKG, especially in patients 65 years or older or with a family history of arrhythmias. [11] In patients with a history of arrhythmias, follow-up EKGs after escitalopram has reached therapeutic levels are also recommended to evaluate for prolongation of the QT interval. A QT interval greater than 500 ms or a change from baseline of more than 60 ms should merit consideration of changing to another antidepressant. [23]

Toxicity

Currently, the highest recommended dose of escitalopram is 20 mg PO daily. Management for out-of-hospital isolated SSRI overdose in patients who are experiencing minor symptoms (regularly less than 5 times their treatment dosage) is recommended at-home observation and close conjunction with a local poison control center. [19]

In an overdose of escitalopram, the most concerning clinical aspect is QT prolongation and a subsequent torsade de pointes arrhythmia, as this could be fatal. In reported ingestions of 300 mg or more of escitalopram, single-dose activated charcoal demonstrably decreased the fraction of absorption by 31% and decreased the risk of abnormal QT interval by 35%. Therefore, the recommendation is to administer a single dose of activated charcoal to patients who have ingested at least 300 mg of escitalopram in an attempted overdose. Cardiac monitoring of patients who receive activated charcoal (overdose of 300 mg or greater) is recommended for 12 hours.[24] In the event of the development of torsade de pointes, administer magnesium sulfate.[25]

In patients with more severe hyperexcitability symptoms, supportive treatment is the mainstay. Besides discontinuing all serotonergic drugs, measures for adequate temperature and blood pressure control should be initiated, agitation control can be achieved with benzodiazepines.  In severe cases of serotonin toxicity patients may require endotracheal intubation and ventilatory support. [19]  For refractory cases to supportive care, medications that are known to have anti-serotonergic properties like cyproheptadine a histamine-1 receptor antagonist, and nonspecific 5-HT1A and 5-HT2A antagonist can be used. Despite this antagonistic effect, it is still unclear its effect on patient clinical outcomes. [26]

Enhancing Healthcare Team Outcomes

Management of depression and anxiety requires an interprofessional team, including physicians, nurses, therapists, and pharmacists. When treating depression and anxiety with escitalopram, the interprofessional healthcare team should communicate and collaborate to achieve the best outcome for the patient. This collaboration can include a thorough review of the patient’s medications to avoid drug interactions and adverse events. Furthermore, pharmacists may monitor the drug level in the blood in cases of overdose, and serum electrolyte levels will be necessary to monitor for disturbances. These coordinated activities and open communication strategies will result in more effective therapeutic outcomes when using escitalopram while minimizing adverse effects. [Level 5]


Article Details

Article Author

Kristen Landy

Article Author

Alan Rosani

Article Editor:

Ryan Estevez

Updated:

9/14/2021 1:07:17 PM

PubMed Link:

Escitalopram

References

[1]

Sanchez C,Reines EH,Montgomery SA, A comparative review of escitalopram, paroxetine, and sertraline: Are they all alike? International clinical psychopharmacology. 2014 Jul;     [PubMed PMID: 24424469]

[2]

Baldwin DS,Asakura S,Koyama T,Hayano T,Hagino A,Reines E,Larsen K, Efficacy of escitalopram in the treatment of social anxiety disorder: A meta-analysis versus placebo. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 2016 Jun;     [PubMed PMID: 26971233]

[3]

Bandelow B,Reitt M,Röver C,Michaelis S,Görlich Y,Wedekind D, Efficacy of treatments for anxiety disorders: a meta-analysis. International clinical psychopharmacology. 2015 Jul;     [PubMed PMID: 25932596]

[4]

Stubbs C,Mattingly L,Crawford SA,Wickersham EA,Brockhaus JL,McCarthy LH, Do SSRIs and SNRIs reduce the frequency and/or severity of hot flashes in menopausal women. The Journal of the Oklahoma State Medical Association. 2017 May;     [PubMed PMID: 28649145]

[5]

Marjoribanks J,Brown J,O'Brien PM,Wyatt K, Selective serotonin reuptake inhibitors for premenstrual syndrome. The Cochrane database of systematic reviews. 2013 Jun 7;     [PubMed PMID: 23744611]

[6]

Kasper S,Sacher J,Klein N,Mossaheb N,Attarbaschi-Steiner T,Lanzenberger R,Spindelegger C,Asenbaum S,Holik A,Dudczak R, Differences in the dynamics of serotonin reuptake transporter occupancy may explain superior clinical efficacy of escitalopram versus citalopram. International clinical psychopharmacology. 2009 May;     [PubMed PMID: 19367152]

[7]

Berger M,Gray JA,Roth BL, The expanded biology of serotonin. Annual review of medicine. 2009     [PubMed PMID: 19630576]

[8]

Yohn CN,Gergues MM,Samuels BA, The role of 5-HT receptors in depression. Molecular brain. 2017 Jun 24;     [PubMed PMID: 28646910]

[9]

Rao N, The clinical pharmacokinetics of escitalopram. Clinical pharmacokinetics. 2007;     [PubMed PMID: 17375980]

[10]

Keks N,Hope J,Keogh S, Switching and stopping antidepressants. Australian prescriber. 2016 Jun     [PubMed PMID: 27346915]

[11]

Dodd S,Malhi GS,Tiller J,Schweitzer I,Hickie I,Khoo JP,Bassett DL,Lyndon B,Mitchell PB,Parker G,Fitzgerald PB,Udina M,Singh A,Moylan S,Giorlando F,Doughty C,Davey CG,Theodoros M,Berk M, A consensus statement for safety monitoring guidelines of treatments for major depressive disorder. The Australian and New Zealand journal of psychiatry. 2011 Sep     [PubMed PMID: 21888608]

[12]

Cipriani A,Santilli C,Furukawa TA,Signoretti A,Nakagawa A,McGuire H,Churchill R,Barbui C, Escitalopram versus other antidepressive agents for depression. The Cochrane database of systematic reviews. 2009 Apr 15;     [PubMed PMID: 19370639]

[13]

Kirpekar VC,Joshi PP, Syndrome of inappropriate ADH secretion (SIADH) associated with citalopram use. Indian journal of psychiatry. 2005 Apr;     [PubMed PMID: 20711296]

[14]

Rondon H,Badireddy M, Hyponatremia StatPearls. 2021 Jan     [PubMed PMID: 29262111]

[15]

Hasnain M,Howland RH,Vieweg WV, Escitalopram and QTc prolongation. Journal of psychiatry     [PubMed PMID: 23791140]

[16]

Beach SR,Celano CM,Sugrue AM,Adams C,Ackerman MJ,Noseworthy PA,Huffman JC, QT Prolongation, Torsades de Pointes, and Psychotropic Medications: A 5-Year Update. Psychosomatics. 2018 Mar - Apr;     [PubMed PMID: 29275963]

[17]

Cooke MJ,Waring WS, Citalopram and cardiac toxicity. European journal of clinical pharmacology. 2013 Apr;     [PubMed PMID: 22996077]

[18]

Scotton WJ,Hill LJ,Williams AC,Barnes NM, Serotonin Syndrome: Pathophysiology, Clinical Features, Management, and Potential Future Directions. International journal of tryptophan research : IJTR. 2019     [PubMed PMID: 31523132]

[19]

Bruggeman C,O'Day CS, Selective Serotonin Reuptake Inhibitor (SSRI) Toxicity 2020 Jan;     [PubMed PMID: 30521236]

[20]

Haddad P, The SSRI discontinuation syndrome. Journal of psychopharmacology (Oxford, England). 1998     [PubMed PMID: 10958258]

[21]

Sabri MA,Saber-Ayad MM, MAO Inhibitors StatPearls. 2021 Jan;     [PubMed PMID: 32491327]

[22]

Petry N,Lupu R,Gohar A,Larson EA,Peterson C,Williams V,Zhao J,Wilke RA,Hines LJ, {i}CYP2C19{/i} genotype, physician prescribing pattern, and risk for long QT on serotonin selective reuptake inhibitors. Pharmacogenomics. 2019 Apr;     [PubMed PMID: 30983508]

[23]

Sheeler RD,Ackerman MJ,Richelson E,Nelson TK,Staab JP,Tangalos EG,Dieser LM,Cunningham JL, Considerations on safety concerns about citalopram prescribing. Mayo Clinic proceedings. 2012 Nov;     [PubMed PMID: 23018033]

[24]

van Gorp F,Duffull S,Hackett LP,Isbister GK, Population pharmacokinetics and pharmacodynamics of escitalopram in overdose and the effect of activated charcoal. British journal of clinical pharmacology. 2012 Mar;     [PubMed PMID: 21883384]

[25]

Thomas SH,Behr ER, Pharmacological treatment of acquired QT prolongation and torsades de pointes. British journal of clinical pharmacology. 2016 Mar;     [PubMed PMID: 26183037]

[26]

Graudins A,Stearman A,Chan B, Treatment of the serotonin syndrome with cyproheptadine. The Journal of emergency medicine. 1998 Jul-Aug     [PubMed PMID: 9696181]