indication

Labeled indications include major depressive disorder (MDD) and generalized anxiety disorder (GAD). Unlabeled indications include treatment of mild dementia-associated agitation in nonpsychotic patients.

pharmacology

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 (5HT_1A, 5HT_1B, 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 5HT_1A autoreceptors. SSRIs bind with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs.

toxicity

Signs of overdose include convulsions, coma, dizziness, hypotension, insomnia, nausea, vomiting, sinus tachycardia, somnolence, and ECG changes (including QT prolongation).

biotransformation

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 reaction.

absorption

The absolute bioavailability of citalopram is about 80% relative to an intravenous dose.

half life

27-32 hours

route of elimination

Following oral administrations of escitalopram, the fraction of drug recovered in the urine as escitalopram and S-demethylcitalopram (S-DCT) is about 8% and 10%, respectively. The oral clearance of escitalopram is 600 mL/min, with approximately 7% of that due to renal clearance. Escitalopram is metabolized to S-DCT and S-didemethylcitalopram (S-DDCT).

drug interactions

Almotriptan: Increased risk of CNS adverse effects

Artemether: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Carvedilol: The SSRI, escitalopram, may increase the bradycardic effect of the beta-blocker, carvedilol.

Desvenlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Eletriptan: Increased risk of CNS adverse effects

Frovatriptan: Increased risk of CNS adverse effects

Ginkgo biloba: Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.

Isocarboxazid: Possible severe adverse reaction with this combination

Ketoprofen: Concomitant therapy may result in additive antiplatelet effects and increase the risk of bleeding. Monitor for increased risk of bleeding during concomitant therapy.

Linezolid: Combination associated with possible serotoninergic syndrome

Lumefantrine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Metoprolol: The SSRI, escitalopram, may increase the bradycardic effect of the beta-blocker, metoprolol.

Naratriptan: Increased risk of CNS adverse effects

Oxycodone: Increased risk of serotonin syndrome

Phenelzine: Possible severe adverse reaction with this combination

Pimozide: The SSRI, escitalopram, increases the effect and toxicity of pimozide.

Propranolol: The SSRI, escitalopram, may increase the bradycardic effect of the beta-blocker, propranolol.

Rasagiline: Possible severe adverse reaction with this combination

Rizatriptan: Increased risk of CNS adverse effects

Selegiline: Possible severe adverse reaction with this combination

Sibutramine: Risk of serotoninergic syndrome

St. John's Wort: St. John's Wort increases the effect and toxicity of the SSRI, escitalopram.

Sumatriptan: Increased risk of CNS adverse effects

Telithromycin: Telithromycin may reduce clearance of Escitalopram. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Escitalopram if Telithromycin is initiated, discontinued or dose changed.

Tiaprofenic acid: Additive antiplatelet effects increase the risk of bleeding. Consider alternate therapy or monitor for increased bleeding.

Ticlopidine: Ticlopidine may decrease the metabolism and clearance of Escitalopram. Consider alternate therapy or monitor for adverse/toxic effects of Ambrisentan if Escitalopram is initiated, discontinued or dose changed.

Tolmetin: Increased antiplatelet effects may enhance the risk of bleeding. Alternate therapy may be considered or monitor for inreased bleeding during concomitant therapy.

Tramadol: Tramadol may increase the risk of serotonin syndrome and seizures.

Tranylcypromine: Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.

Trazodone: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Treprostinil: The prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the antiplatelet agent, Escitalopram. Monitor for increased bleeding during concomitant thearpy.

Trimipramine: The SSRI, Escitalopram, may decrease the metabolism and clearance of Trimipramine. Increased risk of serotonin syndrome. Monitor for changes in Trimipramine efficacy and toxicity if Escitalopram is initiated, discontinued or dose changed.

Triprolidine: The CNS depressants, Triprolidine and Escitalopram, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.

Venlafaxine: Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.

Voriconazole: Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of escitalopram by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of escitalopram if voriconazole is initiated, discontinued or dose changed.

Ziprasidone: Additive QTc-prolongation may occur increasing the risk of life-threatening ventricular arrhythmias and torsade de pointes. Concomitant therapy should be avoided.

Zolmitriptan: Use of two serotonin modulators, such as zolmitriptan and escitalopram, may increase the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.

Zuclopenthixol: Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).