Brands, Medical Use, Clinical Data
- Antidepressive Agents, Second-Generation
- Serotonin Uptake Inhibitors
Brands / Synonyms
Escitalopram Oxalate; Escitalopram [Inn]; Lexapro; Lexapro
For the treatment of major depressive disorder and Generalized Anxiety Disorder (GAD).
Escitalopram is one of a class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs). It is used to treat the depression associated with mood disorders. It is also used on occassion in the treatment of body dysmorphic disorder and anxiety. The antidepressant, antiobsessive-compulsive, and antibulimic actions of escitalopram are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. In vitro studies show that escitalopram is a potent and selective inhibitor of neuronal serotonin reuptake and has only very weak effects on norepinephrine and dopamine neuronal reuptake. Escitalopram has no significant affinity for adrenergic (alpha1, alpha2, beta), cholinergic, GABA, dopaminergic, histaminergic, serotonergic (5HT1A, 5HT1B, 5HT2), or benzodiazepine receptors; antagonism of such receptors has been hypothesized to be associated with various anticholinergic, sedative, and cardiovascular effects for other psychotropic drugs. The chronic administration of escitalopram was found to downregulate brain norepinephrine receptors, as has been observed with other drugs effective in the treatment of major depressive disorder. Escitalopram does not inhibit monoamine oxidase.
Mechanism of Action
The antidepressant, antiobsessive-compulsive, and antibulimic actions of escitalopram are presumed to be linked to its inhibition of CNS neuronal uptake of serotonin. Escitalopram blocks the reuptake of serotonin at the serotonin reuptake pump of the neuronal membrane, enhancing the actions of serotonin on 5HT1A autoreceptors. SSRIs bind with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs.
The absolute bioavailability of citalopram is about 80% relative to an intravenous dose
Signs of overdose include convulsions, coma, dizziness, hypotension, insomnia, nausea, vomiting, sinus tachycardia, somnolence, and ECG changes (including QT prolongation).
Biotrnasformation / Drug Metabolism
Mainly hepatic. Escitalopram undergoes N-demethylation to S-demethylcitalopram (S-DCT) and S-didemethylcitalopram (S-DDCT). CYP3A4 and CYP2C19 are the enzymes responsible for this N-demethylation.
Concomitant use in patients taking monoamine oxidase inhibitors (MAOIs) is contraindicated.
Concomitant use in patients taking pimozide is contraindicated.
LEXAPRO is contraindicated in patients with a hypersensitivity to escitalopram or citalopram or any of the
inactive ingredients in LEXAPRO.
CNS Drugs - Given the primary CNS effects of escitalopram, caution should be used when it is taken in combination
with other centrally acting drugs.
Alcohol - Although LEXAPRO did not potentiate the cognitive and motor effects of alcohol in a clinical trial, as
with other psychotropic medications, the use of alcohol by patients taking LEXAPRO is not recommended. Monoamine
Oxidase Inhibitors (MAOIs) - See Contraindications and Warnings.
Drugs That Interfere With Hemostasis (NSAIDs, Aspirin, Warfarin, etc.)
Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies of the case-control
and cohort design that have demonstrated an association between use of psychotropic drugs that interfere with
serotonin reuptake and the occurrence of upper gastrointestinal bleeding have also shown that concurrent use of an
NSAID or aspirin potentiated the risk of bleeding. Thus, patients should be cautioned about the use of such drugs
concurrently with LEXAPRO.
Cimetidine - In subjects who had received 21 days of 40 mg/day racemic citalopram, combined administration of 400
mg/day cimetidine for 8 days resulted in an increase in citalopram AUC and Cmax of 43% and 39%,
respectively. The clinical significance of these findings is unknown.
Digoxin - In subjects who had received 21 days of 40 mg/day racemic citalopram, combined administration of
citalopram and digoxin (single dose of 1 mg) did not significantly affect the pharmacokinetics of either citalopram
Lithium - Coadministration of racemic citalopram (40 mg/day for 10 days) and lithium (30 mmol/day for 5 days) had
no significant effect on the pharmacokinetics of citalopram or lithium. Nevertheless, plasma lithium levels should be
monitored with appropriate adjustment to the lithium dose in accordance with standard clinical practice. Because
lithium may enhance the serotonergic effects of escitalopram, caution should be exercised when LEXAPRO and lithium
Pimozide and Celexa - In a controlled study, a single dose of pimozide 2 mg co-administered with racemic
citalopram 40 mg given once daily for 11 days was associated with a mean increase in QTc values of approximately 10
msec compared to pimozide given alone. Racemic citalopram did not alter the mean AUC or Cmax of pimozide.
The mechanism of this pharmacodynamic interaction is not known.
Sumatriptan - There have been rare postmarketing reports describing patients with weakness, hyperreflexia, and
incoordination following the use of a selective serotonin reuptake inhibitor (SSRI) and sumatriptan. If concomitant
treatment with sumatriptan and an SSRI (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram,
escitalopram) is clinically warranted, appropriate observation of the patient is advised.
Theophylline - Combined administration of racemic citalopram (40 mg/day for 21 days) and the CYP1A2 substrate
theophylline (single dose of 300 mg) did not affect the pharmacokinetics of theophylline. The effect of theophylline
on the pharmacokinetics of citalopram was not evaluated.
Warfarin - Administration of 40 mg/day racemic citalopram for 21 days did not affect the pharmacokinetics of
warfarin, a CYP3A4 substrate. Prothrombin time was increased by 5%, the clinical significance of which is
Carbamazepine - Combined administration of racemic citalopram (40 mg/day for 14 days) and carbamazepine (titrated
to 400 mg/day for 35 days) did not significantly affect the pharmacokinetics of carbamazepine, a CYP3A4 substrate.
Although trough citalopram plasma levels were unaffected, given the enzyme-inducing properties of carbamazepine, the
possibility that carbamazepine might increase the clearance of escitalopram should be considered if the two drugs are
Triazolam - Combined administration of racemic citalopram (titrated to 40 mg/day for 28 days) and the CYP3A4
substrate triazolam (single dose of 0.25 mg) did not significantly affect the pharmacokinetics of either citalopram
Ketoconazole - Combined administration of racemic citalopram (40 mg) and ketoconazole (200 mg) decreased the
Cmax and AUC of ketoconazole by 21% and 10%, respectively, and did not significantly affect the
pharmacokinetics of citalopram.
Ritonavir - Combined administration of a single dose of ritonavir (600 mg), both a CYP3A4 substrate and a potent
inhibitor of CYP3A4, and escitalopram (20 mg) did not affect the pharmacokinetics of either ritonavir or
CYP3A4 and -2C19 Inhibitors - In vitro studies indicated that CYP3A4 and -2C19 are the primary enzymes
involved in the metabolism of escitalopram. However, coadministration of escitalopram (20 mg) and ritonavir (600 mg),
a potent inhibitor of CYP3A4, did not significantly affect the pharmacokinetics of escitalopram. Because escitalopram
is metabolized by multiple enzyme systems, inhibition of a single enzyme may not appreciably decrease escitalopram
Drugs Metabolized by Cytochrome P4502D6 - In vitro studies did not reveal an inhibitory effect of
escitalopram on CYP2D6. In addition, steady state levels of racemic citalopram were not significantly different in
poor metabolizers and extensive CYP2D6 metabolizers after multiple-dose administration of citalopram, suggesting that
coadministration, with escitalopram, of a drug that inhibits CYP2D6, is unlikely to have clinically significant
effects on escitalopram metabolism. However, there are limited in vivo data suggesting a modest CYP2D6
inhibitory effect for escitalopram, i.e., coadministration of escitalopram (20 mg/day for 21 days) with the tricyclic
antidepressant desipramine (single dose of 50 mg), a substrate for CYP2D6, resulted in a 40% increase in
Cmax and a 100% increase in AUC of desipramine. The clinical significance of this finding is unknown.
Nevertheless, caution is indicated in the coadministration of escitalopram and drugs metabolized by CYP2D6.
Metoprolol - Administration of 20 mg/day LEXAPRO for 21 days in healthy volunteers resulted in a 50% increase in
Cmax and 82% increase in AUC of the beta-adrenergic blocker metoprolol (given in a single dose of 100 mg).
Increased metoprolol plasma levels have been associated with decreased cardioselectivity. Coadministration of LEXAPRO
and metoprolol had no clinically significant effects on blood pressure or heart rate.
Electroconvulsive Therapy (ECT) - There are no clinical studies of the combined use of ECT and escitalopram.
Concomitant Administration with Racemic Citalopram
Citalopram - Since escitalopram is the active isomer of racemic citalopram (Celexa), the two agents should not be