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Escitalopram
Systematic (IUPAC) name
S-(+)-1-[3-(dimethylamino)propyl]- 1-(p-fluorophenyl)- 5-phthalancarbonitrileoxalate
Identifiers
CAS number	128196-01-0
ATC code	N06AB10
PubChem	146570
DrugBank	APRD00683
Chemical data
Formula	C20H21FN2O
Mol. mass	324.392 g/mol (414.40 as oxalate)
Pharmacokinetic data
Bioavailability	80%
Protein binding	~56%
Metabolism	Liver, specifically the enzymes CYP3A4 and CYP2C19
Half life	27–32 hours
Excretion	?
Therapeutic considerations
Pregnancy cat.	C
Legal status	℞ Prescription only
Routes	Oral

Escitalopram (Lexapro, Lexaprin, Cipralex, Sipralexa, Entact and Seroplex)^[1] is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is approved for the treatment of major depressive disorder and generalized anxiety disorder; other indications include social anxiety disorder, panic disorder and obsessive-compulsive disorder. Escitalopram is the S-stereoisomer (enantiomer) of the earlier Lundbeck drug citalopram (Celexa), hence the name escitalopram. Escitalopram is noted for its high selectivity of serotonin reuptake inhibition and, as a result has fewer side effects not related to its serotonergic activity.^[2] The drug is marketed in the United States under the name Lexapro by Forest Laboratories and elsewhere under various brand names by Lundbeck.

Contents 1 History 2 Pharmacology 3 Dosing 4 Side effects and drug interactions 5 Discontinuation symptoms 6 Footnotes 7 External links

Escitalopram was developed in a close cooperation between Lundbeck and Forest Laboratories. Its development was initiated in the summer of 1997, and the resulting new drug application was submitted to the FDA in March 2001. The short time (3.5 years) it took to develop escitalopram can be attributed to the previous extensive experience of Lundbeck and Forest with citalopram, which has similar pharmacology.^[3] The FDA issued the approval of escitalopram for major depression in August 2002 and for generalized anxiety disorder in December 2003. Escitalopram can be considered an example of "lifecycle management"^[4] - the strategy pharmaceutical companies use in order to extend the lifetime of a drug, in this case of the citalopram franchise. Escitalopram is an enantiomer of citalopram, used for the same indication, and for that reason it required less investment and less time to develop. Two years after escitalopram's launch, when the patent on citalopram expired, the escitalopram sales successfully made up for the loss. On May 23, 2006, the FDA approved a generic version of escitalopram by Teva.^[5] However, on July 14 of that year, the U.S. District Court of Delaware decided in favor of Lundbeck regarding the patent infringement dispute and ruled the patent on escitalopram valid.^[6]

Despite the drug's similarity, preclinical as well as various clinical studies (including double-blinded studies—considered the gold standard of clinical evidence) have shown differentiated effects of citalopram and escitalopram^[7] as well as a clinical superiority compared to a variety of other SSRIs, such as paroxetine^[8] especially in severely depressed patients and sertraline. Compared to newer serotonin-norepinephrine reuptake inhibitors such as venlafaxine^[9] and duloxetine^[10] escitalopram was shown to be at least as effective.

Escitalopram acts by increasing intrasynaptic levels of the neurotransmitter serotonin by blocking the re-uptake of the neurotransmitter into the neuron. Of the SSRIs currently on the market escitalopram has the highest affinity for the human serotonin transporter (SERT). Remarkably, another enantiomer of citalopram (R-citalopram) counteracts to a certain degree the serotonin enhancing action of escitalopram. As a result, escitalopram is a more potent antidepressant than citalopram, which is a mixture of escitalopram and R-citalopram. In order to explain this phenomenon, Sanchez proposed that escitalopram enhances its own binding via an additional interaction with another allosteric site on the transporter.^[11] Further research by the same group showed that R-citalopram also enhances binding of escitalopram,^[12] and therefore the allosteric interaction cannot explain the observed counteracting effect. However, in the most recent paper the same authors again reversed their findings and reported that R-citalopram decreases binding of escitalopram to the transporter.^[13] Although allosteric binding of escitalopram to the serotonin transporter is of unquestionable research interest, its clinical relevance is unclear since binding of escitalopram to the allosteric site is at least 1000 times weaker than to the primary binding site.

In vitro studies using human liver microsomes indicated that CYP3A4 and CYP2C19 are the primary isozymes involved in the N-demethylation of escitalopram.

The recommended dosage of Lexapro is 10–40 mg a day, averaging between 10 and 20. Exceptions include the elderly, who should only take up to 10 mg a day, and pregnant women in their third trimester should not use Lexapro at all.^[14] As both Generalized Anxiety Disorder (GAD) and Depression are both considered chronic conditions, treatment is recommended for several months. However, the efficacy of Lexapro over long periods of time has not been studied, therefore consistent re-evaluation of the treatment is recommended for longer periods of treatment.^[14]

Main article: Selective serotonin reuptake inhibitor

The side effect profile of escitalopram is close to that of other SSRIs, with nausea, somnolence, and gastrointestinal side effects reported as relatively common. Escitalopram, like other SSRIs, has been shown to cause sexual side effects in many patients.^[15] Escitalopram does not cause weight gain in comparison to placebo.^{[citation needed]} It may also cause dizziness after exercise in children.^{[citation needed]}

The link between escitalopram treatment and suicidal behavior (suicide, suicide attempt and suicidal ideation) has been studied. A single case report from 2004 has described a patient developing suicidal ideation after beginning treatment with escitalopram, and suicidal ideation disappearing after stopping the treatment.^[16] However, a study reported in 2005 and involving 4091 patient found no indication that escitalopram would provoke suicidal behaviour compared to placebo in patients with major depressive disorder and anxiety disorders.^[17] One genetic study has pointed to that certain genotypes are associated with suicidal ideation during citalopram treatment.^[18]

Escitalopram should be taken with caution when using St John's wort.^[19]

Main article: SSRI discontinuation syndrome

Lexapro discontinuation, particularly abruptly, may cause certain withdrawal symptoms such as paresthesia (for example, electric shock sensations also known as "brain shivers" or "brain zaps"), dizziness and irritability. ^[20]

• Lexapro (Forest Laboratories) Official Lexapro Homepage
• Cipralex (Lundbeck) Official Cipralex Homepage
• Pharmacological information Lexapro

v • d • e Psychoanaleptics: antidepressants (N06A)
MAOIs	Iproclozide • Iproniazid • Isocarboxazid • Nialamide • Pargyline • Phenelzine • Rasagiline • Selegiline • Toloxatone • Tranylcypromine RIMAs: Brofaromine • Beta-carbolines (Harmaline) • Moclobemide
RIs	S RI SS RI (Alaproclate, Citalopram, Dapoxetine, Escitalopram, Etoperidone, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline, Zimelidine) • TCAs/Tetras (Clomipramine, Nefazodone, Trazodone) N RI / A RI Atomoxetine • Maprotiline • Reboxetine • Viloxazine • TCAs/Tetras (Amitriptyline, Amoxapine, Butriptyline, Desipramine/Lofepramine, Dibenzepin, Dothiepin, Doxepin, Imipramine, Iprindole, Melitracen, Nortriptyline, Opipramol, Protriptyline, Trimipramine, Maprotiline) D RI Vanoxerine • Phenmetrazine • TCAs (Amineptine) SN RI Bicifadine • Desvenlafaxine • Duloxetine • Milnacipran • Nefazodone • Venlafaxine ND RI Bupropion SND RI Brasofensine • Tesofensine • Nomifensine
SSREs	Tianeptine
AAs	Tetras (Mianserin, Mirtazapine)