Escitalopram

Article Author:
Kristen Landy
Article Editor:
Ryan Estevez
Updated:
5/6/2020 10:24:33 AM
PubMed Link:
Escitalopram

Indications

Escitalopram, the S-enantiomer of racemic citalopram, is a selective serotonin reuptake inhibitor (SSRI). SSRIs, as a class of drugs, are used for the treatment of depression, anxiety, and other disorders. In the United States, escitalopram is FDA-approved for the use of major depressive disorder and generalized anxiety disorder.[1] Additionally, escitalopram is used off-label by some clinicians for the treatment of social anxiety disorder, obsessive-compulsive disorder, obsessive-compulsive disorder, panic disorder, posttraumatic stress disorder, premenstrual dysphoric disorder, and the vasomotor symptoms of menopause.[1] 

Mechanism of Action

Escitalopram is a selective serotonin reuptake inhibitor. The mechanism of action for SSRIs is to bind to the serotonin transporter protein (SERT) and inhibit the reuptake of serotonin by the presynaptic neuron. This activity potentiates the effect of serotonin in the central nervous system by increasing the amount of serotonin in the synaptic cleft.[2] Serotonin has many functions in the central nervous system, including the regulation of mood. By increasing the activity of serotonin, symptoms of depression, and anxiety symptoms can show improvement with escitalopram therapy.

Escitalopram is the S-enantiomer of citalopram, another SSRI antidepressant medication. The S-enantiomer has demonstrated significantly more potency than the R-enantiomer relative to the serotonin reuptake and inhibition. The half-life of escitalopram is 27 to 32 hours, and it takes 7 to 10 days for it to reach a steady-state in the blood. 

Administration

The administration of escitalopram is via the oral route. 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 increase as needed for symptom control.[3]

Adverse Effects

Escitalopram correlates with a wide variety of adverse effects, most of which are mild, including gastrointestinal upset and sexual dysfunction. Escitalopram can also cause rare but serious adverse reactions, including QT prolongation and serotonin syndrome.

The most common side effects of escitalopram use include sexual dysfunction (primarily decreased libido, anorgasmia, and male ejaculatory delay), insomnia, somnolence, gastrointestinal disturbances (most commonly, nausea), increase in sweating, and fatigue. Escitalopram can also cause electrolyte disturbances such as hyponatremia and hypomagnesemia.[4]

Escitalopram has been observed to cause QT prolongation. QT prolongation is defined as a corrected QT interval on EKG of greater than 500ms or an increase from a baseline interval of more than 60 ms.[5] QT prolongation can cause potentially fatal cardiac arrhythmias, including torsade de pointes.[6] The mechanism by which escitalopram and citalopram cause QT prolongation is a poorly understood phenomenon.[5] It is known, however, to be a dose-dependent relationship, and overdose is a clinical scenario in which prolongation and subsequent arrhythmia are observable.[7]

All antidepressant medications, including escitalopram, have been reported to cause serotonin syndrome. Serotonin syndrome is a potentially life-threatening side effect resulting from an excess amount of serotonin in the central nervous system. This situation 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).

Symptoms of serotonin syndrome may include autonomic instability such as tachycardia, hypertension, dizziness, diaphoresis, flushing, mydriasis, and increased temperature (above 38 Celsius). It can also include nausea, vomiting, diarrhea, and mental status changes, including agitation, delirium, hallucinations, somnolence, and coma. Neuromuscular symptoms can also present, including incoordination, rigidity, clonus, hyperreflexia, tremors, and hypertonicity. There are reports of severe cases presenting with EKG changes and seizures.[4]

Contraindications

The significant contraindications for escitalopram use include assessment of risk for QT prolongation and serotonin syndrome. These are the two most serious adverse drug reactions associated with escitalopram use, and the risk of developing these serious reactions merits evaluation. A history of hypersensitivity to escitalopram or citalopram is also a contraindication.

Monoamine oxidase inhibitor (MAOI) use is contraindicated with escitalopram. Both drugs work to increase serotonin activity and will subsequently increase the risk of developing serotonin syndrome. MAOIs include phenelzine, selegiline, isocarboxazid, and selegiline. Many other drugs can increase the risk of serotonin syndrome if given with escitalopram including other antidepressants, triptans, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, St. John's Wort, as well as drugs that impair the metabolism of serotonin, such as intravenous methylene blue, linezolid, MAOIs and other psychiatric medications. 

Although not an absolute 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. A patient with a family history of long QT syndrome can put the patient at an increased risk of developing a dangerous arrhythmia. Concomitant use of other drugs that can cause prolonged QT syndrome include antipsychotics (especially the older typical antipsychotics) and clinicians need to consider their use with escitalopram carefully.[6]

Finally, CYP2C19 activity is more commonly being evaluated in pharmacogenetics and may play a role in the future of determining contraindication to escitalopram use. The CYP2C19 enzyme 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.[7] 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.[8]

Monitoring

Patients taking escitalopram should receive monitoring for electrolyte disturbances, EKG changes including QT prolongation, and changes in mood and behavior, including suicidality. Escitalopram can cause electrolyte abnormalities, including hyponatremia, and patients at risk of hyponatremia should have their sodium levels monitored while taking escitalopram. For patients at risk or with a family history of arrhythmias, a screening EKG should be obtained before starting escitalopram, and a follow-up EKG should take place after escitalopram has reached therapeutic levels to evaluate for prolongation of the QT interval.[9] 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. Finally, as with all psychotropic medications, routine monitoring for changes in mood and behavior, particularly suicidality, should be performed in patients taking escitalopram.

Toxicity

Currently, the highest recommended dose of escitalopram is 20 mg PO daily. In an overdose of escitalopram, the most concerning clinical aspect is QT prolongation, and subsequent torsade de pointes arrhythmia as this can be deadly. 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%.[10] The recommendation is, therefore, to administer a single dose of activated charcoal to patients who have ingested at least 300 mg of escitalopram in attempted overdose. Cardiac monitoring of patients who receive activated charcoal (overdose of 300 mg or greater) is recommended for 12 hours.[10]

In the event of the development of torsade de pointes, administer magnesium sulfate.[11]

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 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 other medications, to avoid drug interactions and adverse events such as serotonin syndrome. It may also be necessary to obtain an EKG to assess the risk of QT prolongation before beginning and during therapy. 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.


References

[1] Pastoor D,Gobburu J, Clinical pharmacology review of escitalopram for the treatment of depression. Expert opinion on drug metabolism     [PubMed PMID: 24289655]
[2] Florio V,Porcelli S,Saria A,Serretti A,Conca A, Escitalopram plasma levels and antidepressant response. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 2017 Sep;     [PubMed PMID: 28648553]
[3] Rao N, The clinical pharmacokinetics of escitalopram. Clinical pharmacokinetics. 2007;     [PubMed PMID: 17375980]
[4] Bruggeman C,O'Day CS, Selective Serotonin Reuptake Inhibitor (SSRI) Toxicity 2020 Jan;     [PubMed PMID: 30521236]
[5] Hasnain M,Howland RH,Vieweg WV, Escitalopram and QTc prolongation. Journal of psychiatry     [PubMed PMID: 23791140]
[6] 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]
[7] Cooke MJ,Waring WS, Citalopram and cardiac toxicity. European journal of clinical pharmacology. 2013 Apr;     [PubMed PMID: 22996077]
[8] 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]
[9] 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]
[10] 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]
[11] Thomas SH,Behr ER, Pharmacological treatment of acquired QT prolongation and torsades de pointes. British journal of clinical pharmacology. 2016 Mar;     [PubMed PMID: 26183037]