Pharmacology

Escitalopram
Mechanism of action[edit]
Binding profile[55][56]

Site Ki (nM)

SERT 0.8–1.1

NET 7,800

DAT 27,400

5-HT1A >1,000

5-HT2A >1,000

5-HT2C 2,500

α1 3,900

α2 >1,000

D2 >1,000

H1 2,000

mACh 1,240
 hERG 2,600 (IC50)

Escitalopram increases intrasynaptic levels of the neurotransmitter serotonin by blocking

the reuptake of the neurotransmitter into the presynaptic neuron. Over time, this leads to a
downregulation of pre-synaptic 5-HT1A receptors, which is associated with an improvement in passive
stress tolerance, and delayed downstream increase in expression of brain-derived neurotrophic
factor, which may contribute to a reduction in negative affective biases. [57][58]
Of the SSRIs currently available, escitalopram has the highest selectivity for the serotonin
transporter (SERT) compared to the norepinephrine transporter (NET), making the side-effect profile
relatively mild in comparison to less-selective SSRIs.[59]
Escitalopram is a substrate of P-glycoprotein and hence P-glycoprotein inhibitors such
as verapamil and quinidine may improve its blood brain barrier penetrability.[60] In a preclinical study
in rats combining escitalopram with a P-glycoprotein inhibitor, its antidepressant-like effects were
enhanced.

, like other SSRIs, has been shown to affect sexual function, causing side effects such as
decreased libido, delayed ejaculation, and anorgasmia.[27][28]
There is also evidence that SSRIs may cause an increase in suicidal ideation. An analysis
conducted by the FDA found a statistically insignificant 1.5 to 2.4-fold (depending on the statistical
technique used) increase of suicidality among the adults treated with escitalopram for psychiatric
indications.[29][30][31] The authors of a related study note the general problem with statistical approaches:
due to the rarity of suicidal events in clinical trials, it is hard to draw firm conclusions with a sample
smaller than two million patients.[32]
Citalopram and escitalopram are associated with dose-dependent QT interval prolongation[33] and
should not be used in those with congenital long QT syndrome or known pre-existing QT interval
prolongation, or in combination with other medicines that prolong the QT
interval. ECG measurements should be considered for patients with cardiac disease, and electrolyte
disturbances should be corrected before starting treatment. In December 2011, the UK implemented
new restrictions on the maximum daily doses at 20 mg for adults and 10 mg for those older than 65
years or with liver impairment.[34][35] There are concerns of higher rates of QT prolongation
and torsades de pointes compared with other SSRIs.[36][37] The US Food and Drug Administration and
Health Canada did not similarly order restrictions on escitalopram dosage, only on its
predecessor citalopram.[38]
Very common effects[edit]
Very common effects (>10% incidence) include:[39][40][41][4][42]

 Headache (24%)
 Nausea (18%)
 Ejaculation disorder (9–14%)
 Somnolence (4–13%)
 Insomnia (7–12%)
Common (1–10% incidence)[edit]
Common effects (1–10% incidence) include:

 Abnormal dreams
 Anisocoria
 Anorgasmia
 Anxiety
 Arthralgia (joint pain)
 Constipation
 Decreased or increased appetite
 Diarrhea
 Dilated pupils
 Dizziness
 Dry mouth
 Excessive sweating
 Fatigue
 Impotence (erectile dysfunction)
 Libido changes
 Myalgia (muscular aches and pains)
 Paraesthesia (abnormal skin sensation)
 Pyrexia (fever)
 Restlessness
 Sinusitis (nasal congestion)
  Tremor
 Vomiting
 Yawning
Psychomotor effects[edit]
The most common effect is fatigue or somnolence, particularly in older adults, [43] although patients
with pre-existing daytime sleepiness and fatigue may experience paradoxical improvement of these
symptoms.[44] Escitalopram has not been shown to affect serial reaction time, logical reasoning, serial
subtraction, multitask, or Mackworth Clock task performance.[45]
Discontinuation symptoms[edit]
Main article: SSRI discontinuation syndrome
Escitalopram discontinuation, particularly abruptly, may cause certain withdrawal symptoms such as
"electric shock" sensations,[46] colloquially called "brain shivers" or "brain zaps" by those affected.
Frequent symptoms in one study were dizziness (44%), muscle tension (44%), chills (44%),
confusion or trouble concentrating (40%), amnesia (28%), and crying (28%). Very slow tapering was
recommended.[47] There have been spontaneous reports of discontinuation of Lexapro and other
SSRIs and SNRIs, especially when abrupt, leading to dysphoric mood, irritability, agitation, anxiety,
headache, lethargy, emotional lability, insomnia, and hypomania. Other symptoms such as panic
attacks, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), mania,
worsening of depression, and suicidal ideation can emerge when the dose is adjusted down. [48]
Sexual dysfunction[edit]
Some people experience persistent sexual side effects when taking SSRIs or after discontinuing
them.[49] Symptoms of medication-induced sexual dysfunction from antidepressants include difficulty
with orgasm, erection, or ejaculation.[49] Other symptoms may be genital anesthesia, anhedonia,
decreased libido, vaginal lubrication issues, and nipple insensitivity in women. Rates are unknown,
and there is no established treatment.[50]
Pregnancy[edit]
Antidepressant exposure (including escitalopram) is associated with shorter duration of pregnancy
(by three days), increased risk of preterm delivery (by 55%), lower birth weight (by 75 g), and
lower Apgar scores (by <0.4 points). Antidepressant exposure is not associated with an increased
risk of spontaneous abortion.[51] There is a tentative association of SSRI use during pregnancy with
heart problems in the baby.[52] The advantages of their use during pregnancy may thus not outweigh
the possible negative effects on the baby.[52]
Overdose[edit]
Excessive doses of escitalopram usually cause relatively minor untoward effects, such as agitation
and tachycardia. However, dyskinesia, hypertonia, and clonus may occur in some cases.
Therapeutic blood levels of escitalopram are usually in the range of 20–80 μg/L but may reach 80–
200 μg/L in the elderly, patients with hepatic dysfunction, those who are poor CYP2C19
metabolizers or following acute overdose. Monitoring of the drug in plasma or serum is generally
accomplished using chromatographic methods. Chiral techniques are available to distinguish
escitalopram from its racemate, citalopram.[35][53][54]