PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
escitalopram

2D structure

Overview

Generic Names: Cipralex; Escitalopram Oxalate; escitalopram
Trade Names: Lexapro
PharmGKB Accession Id: PA10074

Description

A furancarbonitrile that is one of the serotonin uptake inhibitors used as an antidepressant. The drug is also effective in reducing ethanol uptake in alcoholics and is used in depressed patients who also suffer from tardive dyskinesia in preference to tricyclic antidepressants, which aggravate this condition. PubChem (source: Drug Bank)

Indication

For the treatment of major depressive disorder and Generalized Anxiety Disorder (GAD). (source: Drug Bank)

ATC Therapeutic Category

  • N06AB:Selective serotonin reuptake inhibitors

Pharmacology, Interactions, and Contraindications

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<sub>1A</sub> autoreceptors. SSRIs bind with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs. (source: Drug Bank)

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. <i>In vitro</i> 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<sub>1A</sub>, 5HT<sub>1B</sub>, 5HT<sub>2</sub>), 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. (source: Drug Bank)

Food Interactions

Take without regard to meals. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

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. (source: Drug Bank)

Protein Binding

~56% (source: Drug Bank)

Absorption

The absolute bioavailability of citalopram is about 80% relative to an intravenous dose (source: Drug Bank)

Toxicity

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

Isomeric SMILES Code:

CN(C)CCC[C@@]1(c2ccc(cc2CO1)C#N)c3ccc(cc3)F (source: Drug Bank)

Curated Annotations (Curated Annotation)

  1. rs852977 at chr5:142667687 in NR3C1
    This variant is associated with response to escitalopram and nortriptyline in a study of 760 adult patients with moderate-to-severe depression.
    Related Drugs:
    escitalopram, nortriptyline
    Related Diseases:
    Depression
    Evidence:
    PMID:19365399
  2. rs10482633 at chr5:142730726 in NR3C1
    This variant is associated with response to escitalopram and nortriptyline in a study of 760 adult patients with moderate-to-severe depression.
    Related Drugs:
    escitalopram, nortriptyline
    Related Diseases:
    Depression
    Evidence:
    PMID:19365399
  3. rs11188072 at chr10:96509051 in CYP2C19
    This promoter variant is part of CYP2C19*17 haplotype, which causes increased acitivity and increased transcription of CYP2C19. Patients carrying this allele may exhibit a lack of response to commonly prescribed dosages of certain proton pump inhibitors (PPIs) and antidepressants, due to ultrarapid clearance of these drugs. CYP2C19*17 carriers are more likely to benifit from tamoxifen treatment.
    Variant Name:
    CYP2C19: -3402C>T
    Related Drugs:
    amitriptyline, citalopram, clomipramine, escitalopram, omeprazole, proguanil, tamoxifen
    Evidence:
    PMID:16413245
    PMID:17625515
    PMID:18294333
  4. rs12248560 at chr10:96511647 in CYP2C19
    This promoter variant is part of CYP2C19*17 haplotype, which causes increased acitivity and increased transcription of CYP2C19. Patients carrying this allele may exhibit a lack of response to commonly prescribed dosages of certain proton pump inhibitors (PPIs) and antidepressants, due to ultrarapid clearance of these drugs. CYP2C19*17 carriers are more likely to benifit from tamoxifen treatment.
    Variant Name:
    CYP2C19: -806C>T
    Related Drugs:
    amitriptyline, citalopram, clomipramine, escitalopram, omeprazole, proguanil, tamoxifen
    Evidence:
    PMID:16413245
    PMID:18024866
  5. rs9316233 at chr13:46331356 in HTR2A
    A sudy of 760 adult patients with moderate-to-severe depression, treated with escitalopram found that individuals carrying two minor alleles of rs9316233 variant in the HTR2A gene achieved an improvement that was on average 3.1 MADRS points more than individuals carrying two common alleles during escitalopram treatment. This explains 1.1% of variance (P=0.0016) of the response to escitalopram.
    Related Drugs:
    escitalopram
    Related Diseases:
    Depression
    Evidence:
    PMID:19365399
  6. rs4795541 at chr17:25588443 in SLC6A4
    This study of 135 outpatients with major depressive disorder found no significant associations between SLC6A4 promoter region polymorphisms (5-HTTLPR and rs25531) and response rate or mean change of depressive symptoms during escitalopram treatment, but showed that patients carrying S allele of 5-HTTLPR may have increased risk for some side effects, including headache, induced by escitalopram medication.
    Related Drugs:
    escitalopram
    Related Diseases:
    Depression
    Evidence:
    PMID:19272758
  7. rs4795541 at chr17:25588443 in SLC6A4
    Risk or phenotype-associated allele: -. Phenotype: Those homozygous for the S allele of 5-HTTLPR who also experienced one or more antecedent stressful life events showed a significantly poorer response to escitalopram. Study size: 811. Study population/ethnicity: GENDEP; Europe; White; Patients with Depressive Disorder. Significance metric(s): p = 0.034. Type of association: PD.
    Variant Name:
    5-HTTLPR
    Related Drugs:
    escitalopram
    Related Diseases:
    Depression, Depressive Disorder
    Evidence:
    PMID:20212518
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2C19
  • CO
  •   
  • PK
  •   
  • GN
Publications, Variants
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2D6
  • CO
  •   
  • PK
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
CYP3A
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A4
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A5
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
HTR2A
  •   
  • PD
  •   
  •   
  • GN
Publications, Variants
Phenotype data available Genotype Data Available Literature annotations available Not annotated
NR3C1
  •   
  •   
  •   
  •   
  •   
Variants
No phenotype data No genotype data Literature annotations available Not annotated
SLC6A4
  • CO
  • PD
  •   
  •   
  • GN
Publications, Variants

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

Gene Description
SLC6A4 Uncurated Annotation (source: Drug Bank)

PharmGKB Curated Pathways

The following drugs are in curated knowledge about this drug.

  Drug Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Not annotated
tamoxifen
  •   
  •   
  •   
  •   
  •   
Publications

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Drug Description
almotriptan Uncurated Annotation Increased risk of CNS adverse effects (source: Drug Bank)
carvedilol Uncurated Annotation The SSRI increases the effect of the beta-blocker (source: Drug Bank)
eletriptan Uncurated Annotation Increased risk of CNS adverse effects (source: Drug Bank)
isocarboxazid Uncurated Annotation Possible severe adverse reaction with this combination (source: Drug Bank)
linezolid Uncurated Annotation Combination associated with possible serotoninergic syndrome (source: Drug Bank)
metoprolol Uncurated Annotation The SSRI increases the effect of the beta-blocker (source: Drug Bank)
naratriptan Uncurated Annotation Increased risk of CNS adverse effects (source: Drug Bank)
oxycodone Uncurated Annotation Increased risk of serotonin syndrome (source: Drug Bank)
phenelzine Uncurated Annotation Possible severe adverse reaction with this combination (source: Drug Bank)
pimozide Uncurated Annotation The SSRI increases the effect of the beta-blocker (source: Drug Bank)
propranolol Uncurated Annotation The SSRI increases the effect of the beta-blocker (source: Drug Bank)
rizatriptan Uncurated Annotation Increased risk of CNS adverse effects (source: Drug Bank)
selegiline Uncurated Annotation Possible severe adverse reaction with this combination (source: Drug Bank)
sibutramine Uncurated Annotation Risk of serotoninergic syndrome (source: Drug Bank)
sumatriptan Uncurated Annotation Increased risk of CNS adverse effects (source: Drug Bank)
tramadol Uncurated Annotation Increased risk of serotonin syndrome (source: Drug Bank)
tranylcypromine Uncurated Annotation Possible severe adverse reaction with this combination (source: Drug Bank)
zolmitriptan Uncurated Annotation Increased risk of CNS adverse effects (source: Drug Bank)

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
Anxiety Disorders
  • CO
  •   
  •   
  •   
  •   
Publications
Phenotype data available No genotype data Literature annotations available Not annotated
Depression
  • CO
  • PD
  •   
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Depression, Postpartum
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Depressive Disorder
  • CO
  • PD
  •   
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Depressive Disorder, Major
  • CO
  •   
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Obsessive-Compulsive Disorder
  • CO
  •   
  •   
  •   
  •   
Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB01175
PubChem Compound ID:
146570
PubChem Substance ID:
724297

Common Searches

Search PubMed
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Non-Curated Publications

A list of non-curated publications that mention this drug is available.

PharmGKB integrates drug information from different sources: DrugBank, Open Eye Scientific Software.
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