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] 

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. 

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]

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]

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]