CNS Drugs 2010; 24 (9): 769-796

ADIS DRUG EVALUATION 1172-7047/10/0009-0769/$49.95/0

ª 2010 Adis Data Information BV. All rights reserved.

Escitalopram
A Review of its Use in the Management of Major
Depressive Disorder in Adults
Karly P. Garnock-Jones and Paul L. McCormack
Adis, a Wolters Kluwer Business, Auckland, New Zealand

Various sections of the manuscript reviewed by:

C. Bellantuono, Department of Neuroscience, University of Ancona, Ancona, Italy; C. Bossé, University of
Sherbrooke, Longueuil, Quebec, Canada; P.M. Ellis, Department of Psychological Medicine, Wellington
School of Medicine and Health Sciences, University of Otago, Wellington, New Zealand; W.W. IsHak,
Department of Psychiatry, Cedars-Sinai Medical Center, University of California, Los Angeles and University
of Southern California, Los Angeles, California, USA; A. Menke, Max Planck Institute of Psychiatry, Munich,
Germany.

Data Selection
Sources: Medical literature published in any language since 1980 on ‘escitalopram’, identified using MEDLINE and EMBASE,
supplemented by AdisBase (a proprietary database). Additional references were identified from the reference lists of published articles.
Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.
Search strategy: MEDLINE, EMBASE and AdisBase search terms were (‘escitalopram’ and (‘depressive disorders’ and ‘major’)).
Searches were last updated 23 July 2010.
Selection: Studies in patients with major depressive disorders who received escitalopram. Inclusion of studies was based mainly on the
methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant
pharmacodynamic and pharmacokinetic data are also included.
Index terms: Escitalopram, major depressive disorder, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability,
pharmacoeconomics.

Contents
Abstract. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 770
1. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 770
2. Pharmacological Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 771
2.1 Pharmacodynamic Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 771
2.2 Pharmacokinetic Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 772
2.2.1 Special Patient Populations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 773
2.2.2 Potential Drug Interactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 773
3. Therapeutic Efficacy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 773
3.1 Shorter-Term Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 774
3.1.1 Versus Placebo. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 776
3.1.2 Versus Citalopram . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 776
3.1.3 Versus Other Selective Serotonin Reuptake Inhibitors (SSRIs) . . . . . . . . . . . . . . . . . . . . . . . . . 779
3.1.4 Versus Serotonin-Noradrenaline (Norepinephrine) Reuptake Inhibitors (SNRIs) . . . . . . . . . . 779
3.1.5 Versus Other Antidepressants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 780
3.1.6 In Elderly Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 780
3.2 Longer-Term Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 781
3.2.1 Long-Term Efficacy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 781
3.2.2 Prevention of Relapse or Recurrence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 782
770 Garnock-Jones & McCormack

3.2.3 Extension or Maintenance Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 784

4. Tolerability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 784
4.1 General Tolerability. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 784
4.2 Suicidality. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 786
4.3 Sexual Dysfunction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 787
4.4 Treatment Discontinuation-Emergent Adverse Events. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 787
4.5 Post-Marketing Surveillance Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 788
5. Pharmacoeconomic Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 788
6. Dosage and Administration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 789
7. Place of Escitalopram in the Management of Major Depressive Disorder in Adults . . . . . . . . . . . . . . . 790

Abstract Escitalopram (escitalopram oxalate; Cipralex, Lexapro), a selective serot-

onin reuptake inhibitor (SSRI) indicated for the treatment of major depressive
disorder (MDD), demonstrates a highly selective and potent, dose-dependent
inhibition of the human serotonin transporter, inhibiting serotonin reuptake into
presynaptic nerve terminals and thus increasing serotonergic activity in the CNS.
With regard to primary endpoints (such as improved scores on the Mont-
gomery-Åsberg Depression Rating Scale [MADRS] and the Hamilton Depression
Rating Scale [HAM-D]), escitalopram was generally more effective than placebo,
at least as effective as citalopram, and generally at least as effective as other
comparator drugs, including the SSRIs fluoxetine, paroxetine and sertraline, the
serotonin-noradrenaline (norepinephrine) reuptake inhibitors (SNRIs) venlafax-
ine extended release and duloxetine, and the aminoketone bupropion in adult
patients with MDD in short-term, well designed trials. Moreover, it demonstrated
a rapid onset of antidepressant action. Escitalopram was also found to be cost
effective in several studies, dominating other SSRIs and venlafaxine extended
release.
Maintenance therapy is commonly required to prevent recurrence of depres-
sion. Long-term trials corroborated short-term results, with escitalopram de-
monstrating greater efficacy than placebo in relapse prevention. Additionally,
escitalopram was at least as effective as citalopram, paroxetine and duloxetine in
long-term comparative trials.
Escitalopram has a predictable tolerability profile with generally mild to
moderate and transient adverse events, and a low propensity for drug interac-
tions. Sexual dysfunction with escitalopram treatment appeared to occur to a
similar or lower extent to that with paroxetine (another SSRI), to a similar or
greater extent to that with the SNRI duloxetine, and to a greater extent than that
with the aminoketone bupropion.
Thus, escitalopram is an effective and generally well tolerated treatment for
moderate to severe MDD. Escitalopram, like other SSRIs, is an effective first-line
option in the management of patients with MDD.

1. Introduction ability).[1-3] The WHO has estimated that depression

Major depressive disorder (MDD) is projected
to move from fourth (in 1990) to second place, after
ischaemic heart disease, in the ranking of contribu-
tors to the global burden of non-infectious disease
by 2020 (as measured by years lived with dis-
affects, at any one time, almost 340 million people
globally and 18 million people in the US,[1] and has
a lifetime prevalence in the US of »17%.[1,2,4] The
risk of developing depression is approximately twice
as high in women as in men.[5] A total of 75–90%
of patients with depression are estimated to have

ª 2010 Adis Data Information BV. All rights reserved. CNS Drugs 2010; 24 (9)
Escitalopram: A Review
multiple episodes,[1] and depression often occurs
comorbidly with anxiety and medical illnesses.[4]
While depression is more frequently observed in
younger adults than among the elderly, the number
of older adults with major depression is increas-
ing.[3] Moreover, depression is often associated with
complications of other illnesses in elderly patients.[3]
Major depression is associated with a significant
societal impact, with an estimated 27.2 work days
lost per worker per year in the US; across the US
civilian work force, 225.0 million work days and
$US36.6 billion in salary-equivalent productivity
are lost per year.[2] Between 1995 and 2005, the
number of hospital outpatient visits associated
with major depression rose by »48% in the US.[2]
Antidepressant drugs include tricyclic antide-
pressants (TCAs) [e.g. amitriptyline], monoamine
oxidase inhibitors (MAOIs) [e.g. phenelzine],
selective serotonin reuptake inhibitors (SSRIs)
[e.g. citalopram] and serotonin-noradrenaline (nor-
epinephrine) reuptake inhibitors (SNRIs) [e.g.
venlafaxine], as well as novel agents (e.g. the amino-
ketone bupropion).[5] SSRIs are currently con-
sidered among the first-line treatments for MDD
in several countries,[5-7] partially because they have
been shown to be associated with fewer adverse
events than TCAs.[5,7,8]
Racemic citalopram, a commonly used SSRI, is
made up of the therapeutically active S-enantiomer,
now separately developed as escitalopram (esci-
talopram oxalate; Cipralex, Lexapro), and the
largely therapeutically inactive R-enantiomer.[9,10]
This article provides an overview of the pharmaco-
logical properties of escitalopram and reviews
the clinical trial data available on the efficacy
and tolerability of the drug in the management of
adult (including elderly) patients with MDD.
Escitalopram is also indicated for the treatment
of generalized anxiety disorder (GAD),[11,12] panic
disorder (PD),[12] social anxiety disorder (SAD)[12]
and obsessive-compulsive disorder (OCD),[12] but
these indications are beyond the scope of this
review. Escitalopram in MDD[9,10] and anxiety
disorders[9,13] has been previously reviewed, and a
pharmacoeconomic review of its use in depres-
sion[14] has also been published. The use of esci-
talopram in adolescents with MDD has been
covered elsewhere[15] and is not discussed here.
ª 2010 Adis Data Information BV. All rights reserved.
771
2. Pharmacological Properties
The pharmacological properties of escitalopram
have been extensively reviewed elsewhere;[9,10,13]
only a brief overview is provided in this section.
2.1 Pharmacodynamic Properties
Escitalopram is believed to exert its antidepres-
sant effect through its highly potent and selective,
dose-dependent inhibition of the human serotonin
transporter (SERT) [table I], thus inhibiting sero-
tonin reuptake into presynaptic nerve terminals and
potentiating serotonergic activity in the CNS.[9-13]
Escitalopram is the most selective SSRI with
regard to binding to SERT,[10,13] and is associated
with an increase in extracellular serotonin levels
in animal studies[10,13] (table I). Escitalopram
occupancy on midbrain SERT is correlated with
a decrease in depression in patients with MDD
(table I);[16] escitalopram is also associated with
antidepressant effects, decreased aggression and in-
creased serotonin-associated behavioural changes
in animal models (table I).[10,13] Other effects asso-
ciated with escitalopram are presented in table I.
Two citalopram binding sites have been sug-
gested for SERT: the primary, high-affinity, ac-
tive site and the low-affinity, allosteric site, which
modulates the ability of ligands to bind to the
primary site.[10,13] Escitalopram has a 1000-fold
lower affinity for the SERT allosteric site than
the SERT primary site.[12] When escitalopram is
bound to the primary site, serotonin reuptake
is inhibited.[10,13] Preliminary evidence suggests
that if R-citalopram is bound to the allosteric site,
the time that escitalopram is bound to the pri-
mary site decreases, thus decreasing inhibition,
and if escitalopram is bound to the allosteric site,
the time that escitalopram is bound to the primary
site increases, thus increasing inhibition.[10,13] This
interference by R-citalopram of the escitalopram-
associated serotonin reuptake inhibition is pre-
sumed to occur via a conformational protein
change, and may explain the modulatory role
observed with coadministration of R-citalopram
and escitalopram (table I).[10,13]
The coadministration of a single dose of pi-
mozide 2 mg and 11 days’ treatment with racemic
CNS Drugs 2010; 24 (9)
772 Garnock-Jones & McCormack

Table I. Overview of the pharmacodynamic properties of escitalopram (ESC)

Functional effects
»25–40 times more potent at SERT than R-CIT[17,18] (1.4–5.4-fold more potent than CIT[17-20]) in in vitro and ex vivo studies
More selective inhibitor of 5-HT reuptake than of NA (»2600 times) or DA (>40 000 times) reuptake, and more selective than CIT and other
SSRIs for binding to SERT vs NAT or DAT[10,13]
No or low affinity for other receptors (including serotonergic 5-HT1–7, dopamine D1–5, a- and b-adrenergic, histamine H1–3, muscarinic M1–5,
benzodiazepine and opioid receptors)[11,12] and ion channels (including Na+, K+, Cl- and Ca2+)[11]
Greater increase than CIT in extracellular 5-HT levels; R-CIT has no direct effect on 5-HT levels and counteracts the ESC-induced
increase[10,13]a
»4 times more potent than CIT in suppression of firing activity of presumed 5-HT neurons in the dorsal raphe nucleus, and faster return to
control rate; this faster desensitization of autoreceptors may account for the earlier onset of action of ESC compared with CIT[10,13]a
SERT occupancy by ESC in healthy male volunteers is disrupted by R-CIT after multiple[21] but not single[22] doses of CIT, potentially due to a
slower clearance of R-CIT than ESC[23]
Behavioural effects
»4 times as potent as CIT at reducing aggressive behaviour[10,13]a
ESC-associated behavioural effects are inhibited by R-CIT[10,13]a
ESC-mediated recovery from a chronic stress model of depression was correlated to hippocampal cytogenesis[13]a
An increase in ESC midbrain SERT occupancy was significantly correlated with a decrease in HAM-D17 scores in patients with MDD[16]
Other effects
Associated with antiplatelet activity in human blood samples[24] and normalization of platelet activation in patients with MDD[25]
ESC and CIT were associated with similar increases in HPA axis activity, but no change in plasma prolactin levels, in healthy volunteers[10,13]
No effect on driving performance and psychomotor functioning;[10,13] no clinically significant effect on ECG measures or blood pressure[11]
No effect on BDNF levels in one study,[26] but ESC normalized BDNF levels that were reduced in depressed patients in another study[27]
Associated with significant (p < 0.05) improvement in identity recognition memory for faces acquired with angry expressions, but no difference
for faces acquired with happy expressions, in elderly (aged >65 years) patients with MDD[28]
a Animal studies.
5-HT = serotonin (5-hydroxytryptamine); BDNF = brain-derived neurotrophic factor; CIT = racemic citalopram; DA = dopamine; DAT = human
dopamine transporter; HPA = hypothalamic-pituitary-adrenal; MDD = major depressive disorder; NA = noradrenaline (norepinephrine);
NAT = human noradrenaline transporter; R-CIT = R-citalopram; SERT = human serotonin transporter; SSRIs = selective serotonin reuptake
inhibitors.

citalopram 40 mg/day resulted in an increase in (tmax) of »4 hours at steady state.[29] The steady-
corrected QT interval time of »10 ms compared state area under the plasma concentration-time

with pimozide alone.[11]
2.2 Pharmacokinetic Properties
Data on the pharmacokinetics of oral escita-
lopram were taken from the US prescribing
information,[11] the EU summary of product char-
acteristics (SPC)[12] and fully published articles.[29-32]
The pharmacokinetics of escitalopram are
linear and dose-proportional over the approved
dosage range, and can be accurately described by
a one-compartment model with first-order elimina-
tion.[11,12] Steady state is reached within 10 days.[29]
Escitalopram is rapidly absorbed with the max-
imum plasma concentration (Cmax; 20.6 ng/mL
with 10 mg/day) being attained after a mean time


curve from time 0 to 24 hours (AUC24) with es-
citalopram 10 mg was 360.1 ng h/mL (2.3- to
2.6-fold higher than after a single 10 mg dose) and
the apparent volume of distribution was 1255 L.[29]
The mean bodyweight-normalized volume of
distribution for oral escitalopram was »20 L/kg,
with a range of 12–36 L/kg.[29] The plasma pro-
tein binding of escitalopram is »56%;[11] <80% of
escitalopram plus its metabolites are plasma protein-
bound.[12] The absolute bioavailability of escitalo-
pram is expected to be »80%,[12] similar to racemic
citalopram.[11,12] The tablet and oral solution for-
mulations of escitalopram are bioequivalent.[11,33]
The major metabolites of escitalopram are
S-demethylcitalopram (S-DCT) and S-didemethyl-
citalopram (S-DDCT),[11,12] with the primary

ª 2010 Adis Data Information BV. All rights reserved. CNS Drugs 2010; 24 (9)
Escitalopram: A Review
route of biotransformation to S-DCT mediat-
ed by cytochrome P450 enzyme (CYP) 2C19 or
CYP3A4;[11,12] CYP2D6 also contributes towards
biotransformation.[12] S-DCT demethylation to
S-DDCT is preferentially mediated by CYP2D6
and a non-CYP-mediated reaction.[30] Unchanged
escitalopram was the most common compound
in the plasma, and S-DCT concentration was ap-
proximately one-third of the unchanged escitalo-
pram concentration at steady state.[11,12] S-DDCT
levels were not detectable in most subjects[11] or
were <5% of escitalopram concentrations.[12] Es-
citalopram metabolites, while pharmacologically
active,[12] do not significantly contribute to the ther-
apeutic actions of escitalopram, with escitalopram
‡7 and ‡27 times more potent than S-DCT and
S-DDCT.[11] Biotransformation of escitalopram is
mainly hepatic.[11] Other biotransformations of es-
citalopram include deamination and dehydrogena-
tion to a propionic acid derivative and N-oxidation
and glucuronide conjugation.[30] There was no evi-
dence of interconversion from S-enantiomers to
R-enantiomers in healthy volunteers.[29]
The pharmacokinetics of a single, oral dose of
escitalopram 10 mg or its metabolite S-DCT were
not significantly altered when given concomi-
tantly with food.[29]
Escitalopram and its metabolites are partially
excreted as glucuronides.[12] The proportion of oral
escitalopram excreted in the urine as unchang-
ed drug was »8%;[11] the proportion excreted as
S-DCT was »10%.[11] Approximately 7% of the
oral clearance (»35 L/h [»600 mL/min]) was due
to renal clearance.[11,12] The elimination half-life
for escitalopram was »30 hours;[11,12] the major
metabolites had significantly longer half-lives
(approximately twice as long for S-DCT[29,30]).[12]
Elimination of escitalopram and its major meta-
bolites is assumed to occur via the hepatic and
renal routes; metabolites in the urine make up the
major part of the dose.[12]
2.2.1 Special Patient Populations
Elderly volunteers aged 65–80 years had higher
Cmax, AUC24 and half-life values, and lower
clearance than younger adult volunteers aged
18–35 years.[30] Sex had no effect on escitalopram
pharmacokinetics.[11,12]
ª 2010 Adis Data Information BV. All rights reserved.
773
While there are no data for escitalopram
pharmacokinetics in patients with renal impair-
ment, reduced renal function in recipients of ci-
talopram was associated with a longer half-life,
a reduced oral clearance and a minor increase
in exposure.[11,12] Values for citalopram half-life
(49.5 hours) and renal clearance (0.03 L/h/kg)
were significantly longer (p < 0.05) and lower
(p < 0.005), respectively, in seven patients with
moderate renal impairment (creatinine clearance
10–53 mL/min) who received a single dose of oral
citalopram 20 mg than in 12 healthy volunteers
receiving a single dose of oral citalopram 40 mg
(36.8 hours and 0.05 L/h/kg, respectively).[34]
Reduced hepatic function was associated with
a 2-fold longer escitalopram half-life, increased
AUC¥ (52–69% higher for mild to moderate im-
pairment) and reduced clearance (19–36% lower
for mild to moderate impairment).[12,31]
Poor metabolizers with respect to CYP2C19
had a 2-fold increase in escitalopram AUC¥ va-
lues compared with normal metabolizers.[12,32]
Poor CYP2D6 metabolizers did not have any
significant change in escitalopram exposure.[12]
2.2.2 Potential Drug Interactions
Since escitalopram is metabolized by CYP2C19,
concomitant administration of escitalopram with
CYP2C19 inhibitors (e.g. omeprazole, cimetidine,
fluvoxamine, lansoprazole and ticlopidine) may in-
crease the plasma concentration of escitalopram.[11,12]
Escitalopram is a weak inhibitor of CYP2D6
and may increase the plasma concentrations of
CYP2D6 substrates (e.g. desipramine and meto-
prolol) when coadministered.[11,12]
As escitalopram is metabolized by several en-
zyme systems, it was hypothesized that inhibition
of a single enzyme may not decrease escitalopram
clearance to a clinically significant degree; co-
administration of escitalopram with ritonavir, a
potent inhibitor of CYP3A4, did not have any
significant effect on the pharmacokinetic para-
meters of either drug.[11]
3. Therapeutic Efficacy
The efficacy of oral escitalopram has been ex-
tensively studied, in both the short-[35-53] and
CNS Drugs 2010; 24 (9)
774
Table II. Definitions and descriptions of efficacy assessments as used in clinical trials
Assessment (abbreviation)
Clinical Global Impressions-Improvement
scale (CGI-I)
Clinical Global Impressions-Severity scale
(CGI-S)
Hamilton Anxiety Rating Scale (HAM-A)
Hamilton Depression Rating Scale (HAM-D)
HAM-D17 Maier subscale
Medical Outcomes Study 36-item Health
Survey (SF-36)
Montgomery-Åsberg Depression Rating
Scale (MADRS)
MADRS core depression subscale
Quality of Life Enjoyment and Satisfaction
Questionnaire (Q-LES-Q)
Q-LES-Q short form
Recurrence
Relapse
Remission
Response
HR-QOL = health-related quality of life.
long-term[45,54-62] treatment of adults with MDD.
Only well designed trials involving >100 patients are
discussed here. Commonly used assessment scales
as well as response, remission, recurrence and re-
lapse are defined in table II. See tables III–VII for
double-blind treatment details not covered in the
text.
3.1 Shorter-Term Treatment
The efficacy of escitalopram in the shorter-
term (£12 weeks’) treatment of adults with MDD
(n = 195–684/trial) has been investigated in nu-
merous randomized, double-blind, multicentre
trials,[35-53] with comparisons between escitalo-
pram and placebo (section 3.1.1),[35-40] citalopram
(section 3.1.2)[35,37,41-44] and other antidepres-
sants (sections 3.1.3–3.1.5),[36,38,41,45-51] as well as
ª 2010 Adis Data Information BV. All rights reserved.
Garnock-Jones & McCormack
Description
A 7-point, clinician-rated scale measuring change in illness severity. Scores range from 1
(very much improved) to 7 (very much worse)
A 7-point, clinician-rated scale measuring illness severity. Scores range from 1 (normal) to 7
(extremely ill)
A 14-item, clinician-rated scale to assess the severity of anxiety symptoms. Each item is rated
from 0 to 4. A higher score indicates a greater level of anxiety
A 17- (HAM-D17) or 24-item (HAM-D24), clinician-rated scale to assess severity of depression.
Each item is rated from 0 to 2 or 4. A higher score indicates a greater level of depression
Assesses the severity of core emotional symptoms of depression. Items 1 (depressed mood),
2 (guilt), 7 (work and activities), 8 (retardation), 9 (agitation) and 10 (psychic anxiety) on the
HAM-D17 scale
A 36-item scale to assess HR-QOL. Higher scores indicate a better HR-QOL
A 10-item, clinician-rated scale to assess depression states. Each item is rated from 0 to 6.
A higher score indicates a greater level of depression
Assesses the severity of core symptoms of depression. Items 1 (apparent sadness),
2 (reported sadness), 3 (inner tension), 7 (lassitude), 8 (inability to feel) and 9 (pessimistic
thoughts) on the MADRS scale
A 93-item scale to assess HR-QOL. Higher scores indicate a better HR-QOL
A 16-item scale, derived from the Q-LES-Q. The total score is the sum of the first 14 items.
Higher scores indicate a better HR-QOL
Defined as a MADRS total score ‡22 or treatment withdrawal due to insufficient response[59]
Defined as a MADRS total score ‡22,[57-59] treatment withdrawal due to insufficient
response,[57,59] or lack of efficacy[58]
Defined as a MADRS total score £10,[39,47,49,50,53] £12[37,40,42,44,45,51,52,54-56,58,61,62] a
HAM-D17 total score <7,[46] £7[36,38,43,60] or <8,[41] or a CGI-S score £2[58]
Defined as a ‡50% decrease in MADRS total score,[35,37,39,40,42,44,45,47,49-56,58,61,62] a ‡50%
decrease in HAM-D17 total score,[36,38,41,43,46] or a CGI-I score £2[58] at endpoint
investigations into treatment of elderly patients
(section 3.1.6).[52,53] Most studies were fully pub-
lished;[35-38,40-47,49-53] two studies were available
as abstracts,[39,48] with further information taken
from the sponsor’s website.[63,64] Analyses in one
trial[44] compared the efficacy of escitalopram
10 mg/day with that of citalopram 10 mg/day;
these are not equivalent dosages and comparative
efficacy was compromised.
Eligible patients were aged 18–65,[35,37,40-43,46,48,49]
18–80,[47,50] 18–85,[51] ‡18[36,38,45] or 25–45[44] years
(elderly patients were aged ‡60[53] or ‡65[52] years)
and had a DSM-IV[35-38,40,42-47,49-53,64,65] or an
International Statistical Classification of Diseases
and Related Health Problems, 10th Revision (ICD-
10)[41] diagnosis of MDD (confirmed by the Mini
International Neuropsychiatric Interview[38,47,53]),
with moderate to severe depression ratings
CNS Drugs 2010; 24 (9)
Escitalopram: A Review
(MADRS total score ‡22 and HAM-D24 item 1
[depressed mood] score ‡2;[35] MADRS total score
‡18,[51] ‡22,[38,47,53] ‡25,[44] ‡26[50] or ‡30;[42,48]
MADRS total score ‡22 and £40;[37,40,45,52]
HAM-D17 total score ‡19,[36] ‡18[41,46] or ‡17;[43]
or HAM-D24 total score ‡20[49] or ‡30[39]). Ad-
ditional criteria included a current major depres-
sive episode of ‡4 weeks’,[35,53] ‡12 weeks’[50] or
‡12 weeks’ and £2 years’[36] duration, a MADRS
total score at baseline within 25% of the score at
screening,[50] a Mini-Mental State Examination
(MMSE) score ‡22[52] or ‡24,[53] a CGI-S score
‡4[38,46,50] and normal orgasm function (and en-
gaged in sexual activity leading to orgasm at least
once every 2 weeks).[36] One study was in Chinese
patients.[43]
Patients were excluded if, among other things,
they were considered to be treatment resistant to
certain antidepressants[38,41,45,47,49,50,52,53] or had
recent use of certain treatments for depres-
sion,[38,43,44,47,49-51,53] they had chronic suicidal
ideation and behaviour[41,43] or a suicide attempt
in the past 6 months[36] or 1 year,[35,50,53] were
considered to be at risk of suicide,[38,45-47,49] or
had active suicidal ideation (MADRS item 10
score ‡5).[35,37,40,45,50-53] Certain concomitant
treatments were not permitted, including most
psychotropic drugs.[35,37,38,40,41,44-47,49,50,52,53]
The primary efficacy endpoint in most stud-
ies was the mean change from baseline in
MADRS total score at endpoint (week 6,[44]
8[35,37,40,42,45,47,49-52] or 12[53]) or week 2,[63] or the
mean change from baseline in HAM-D17 total score
at endpoint (week 6[43] or 8[46]). Noninferiority of
escitalopram in three studies[45,46,51] was demon-
strated if the upper (90%[45,51]) confidence inter-
val (CI) of the difference in change from baseline
in MADRS total score[45,51] or HAM-D17 total
score[46] between escitalopram and comparator
(venlafaxine extended release,[51] paroxetine[45] or
fluoxetine[46]) was within the prespecified 3-point
margin. One study’s[38] primary endpoint was the
proportion of patients with onset of efficacy (a sus-
tained 20% decrease from baseline in HAM-D17
Maier subscale score) at week 2. Noninferior-
ity of duloxetine to escitalopram in this study was
demonstrated if the lower bound of the 97.5%
one-sided CI of the difference between duloxetine
ª 2010 Adis Data Information BV. All rights reserved.
775
and escitalopram recipients in rate of onset of
antidepressant efficacy at week 2 was greater than
-10%.[38] One study[36] had a tolerability-based
primary endpoint (sexual dysfunction; see sec-
tion 4), but also had a primary efficacy endpoint
(change from baseline in HAM-D17 total score
at week 8).[36] One study had the number of days
to premature treatment discontinuation (all cau-
ses) as the primary endpoint.[48] Another study[41]
had five co-primary efficacy measures: change in
HAM-D17 total score, change in CGI-S score,
CGI-I score, response rate and remission rate at
endpoint (week 4).
In the general adult population at baseline, the
mean age was 34–45 years[35-38,40-51,63] and 51–76%
of patients were female.[35-38,40-47,49-51,63,64] Where
stated, 11–70%[35,42,44,49] of patients had recurrent
disease, 3% had a history of suicide attempts,[41]
the current episode had lasted a mean of
40–41 weeks[36] or a median of 4–5.5 months,[41]
the mean duration of MDD was »9 years,[49]
»58%[37] and 59%[40] of patients had a MADRS
total score ‡22 and £29, »56% had a MADRS
total score ‡18 and £29,[51] »42%[37] and 41%[40]
had a MADRS total score ‡30, 58%[42] and 65%[44]
had a MADRS total score ‡35, and 75% had a
HAM-D17 total score >21.[41]
Among elderly patients at baseline, the mean
age was 68–75 years[52,53] and 59–76%[52,53] of pa-
tients were female. Where stated, 78% of patients
were aged under 75 years.[53]
Baseline characteristics were generally similar
between treatment groups;[35-38,40-47,49-53] two stud-
ies reported significant (p < 0.05[46] and p < 0.01[49])
differences in proportions of female patients be-
tween treatment groups,[46,49] one study reported
a significant (p = 0.036) difference in mean age,[38]
and escitalopram recipients in one study had a sig-
nificantly (p = 0.045) higher baseline HAM-D score
than venlafaxine extended-release recipients.[49]
Results were calculated using the intent-to-
treat (ITT)[41] or modified ITT (mITT) popula-
tion,[35-40,42-53] using last-observation carried
forward (LOCF) imputation[35-53] (one study[38]
presented response and remission rates using
LOCF imputation, but did not state imputa-
tion methods for the other analyses, another[46]
presented response and remission rates using
CNS Drugs 2010; 24 (9)
776
observed case analyses, but used LOCF for other
endpoints).
Some short-term studies[37,38,40,45,52] continued
on into extension or maintenance studies,[45,60-62]
discussed in section 3.2.
3.1.1 Versus Placebo
Treatment with escitalopram 10–20 mg/day for
£8 weeks was generally more effective than pla-
cebo in the treatment of MDD in several well
designed trials.[35-40]
The reduction from baseline to endpoint in
MADRS total score (primary endpoint in several
trials[35,37,40]) was significantly greater in escitalo-
pram recipients than in placebo recipients[35,37,39,40]
(table III). Additionally, while the reduction from
baseline to week 2 in MADRS total score was not
significantly different between escitalopram and
placebo recipients in the one trial where it was the
primary endpoint (table III),[39] it was significantly
(p £ 0.05) improved in three other trials.[35,37,40]
HAM-D total scores (primary efficacy end-
point in two trials[36]) improved among escitalo-
pram recipients to a significantly greater extent
than in placebo recipients in two[35,36] of the four
trials investigating this endpoint (tables III[35]
and IV[36,38]).[35,36,38]
Escitalopram demonstrated a rapid onset of
antidepressant action.[35,37-40] A total of 35.2%
of escitalopram and 21.5% of placebo recipients
reported a sustained 20% decrease from base-
line in HAM-D17 Maier subscale score at week 2
(p = 0.008).[38] In addition, where reported, signif-
icant (p £ 0.05) differences between escitalopram
and placebo recipients in mean change from
baseline in primary endpoints (MADRS[35,37,39,40]
or HAM-D17[38] total scores) were observed from
week 1,[37,38] 2[35,40] or 4[39] onwards (the differ-
ence was significant at week 1, but not at week 3,
in one trial[38]).
The response rate was significantly higher
in escitalopram than in placebo recipients in
all but two[36,38] trials (tables III[35,37,39,40] and
IV[36,38]).[35-40] Results were mixed for remission
rates: escitalopram recipients had a significantly
higher rate than placebo recipients in two stud-
ies,[36,40] but not in the other three studies report-
ing remission rates[36-38] (tables III[37,40] and IV[36,38]).
ª 2010 Adis Data Information BV. All rights reserved.
Garnock-Jones & McCormack
Other efficacy measures, including CGI-I,[35,37,39,40]
CGI-S,[35,37,38] and Q-LES-Q short form[35] scores,
were also generally significantly (p £ 0.05) improv-
ed among escitalopram versus placebo recipients
across studies in which these measures were as-
sessed;[35-40] however, between-group differences
were not significant for CGI-I in one study[36] and
for CGI-S in two studies.[36,40] In addition, anxiety
measured on the HAM-A was investigated in two
trials; escitalopram 10 and 20 mg/day were both
associated with significantly greater improvements
in HAM-A than placebo in one trial (p < 0.05 and
p < 0.01, respectively),[35] but the other trial show-
ed no treatment difference between escitalopram
and placebo recipients.[38]
With regard to the primary endpoints (e.g. im-
proved scores on the MADRS and the HAM-D
scales), the active comparators (citalopram, bupro-
pion, duloxetine) used in the placebo-controlled
trials were more effective than placebo in some,[35,38]
but not all,[36,37] trials (see tables III and IV).
3.1.2 Versus Citalopram
Escitalopram 10–20 mg/day treatment for
4–8 weeks was at least as effective as citalopram
in the treatment of MDD in five well designed
trials.[35,37,41-44]
Escitalopram recipients had a significantly
(p < 0.05) greater decrease from baseline to end-
point in MADRS total score than citalopram
recipients in two studies[42,44] (table III). The
studies not powered for escitalopram-citalopram
comparisons[35,37] showed no significant differ-
ence between groups in this measure (table III).
The reduction in MADRS total score was the pri-
mary endpoint in all four of these studies.[35,37,42,44]
A significant (p £ 0.05) difference between escita-
lopram and citalopram recipients in mean change
from baseline in MADRS total score was observed
from week 1 onwards in one study.[44] Another study
reported no significant difference between escitalo-
pram and citalopram recipients in mean change
from baseline in MADRS total score at weeks 1 and
4; however, there was a significant between-group
difference at endpoint (week 8; table III).[42]
The change from baseline in MADRS core de-
pression subscale score was significantly (p < 0.001)
greater among escitalopram recipients than among
CNS Drugs 2010; 24 (9)
Escitalopram: A Review 777

Table III. Efficacy of escitalopram (ESC) versus placebo (PL) or selective serotonin reuptake inhibitors (SSRIs) in patients (pts) with major
depressive disorder. Short-term, randomized, double-blind, multicentre studies in pts with moderate to severe disease.[35,37,39-42,44-47] Drugs
were given once daily (od), unless otherwise specified. Results from PL-controlled trials with duloxetine or bupropion comparator arms are
presented in table IV. Results are for the intent-to-treat[41] or the modified intent-to-treat populations,[35,37,39,40,42,44-47] using last observation
carried forward imputation.[35,37,39-42,44-47] See table II for definitions of efficacy parameters
Study (duration) Target dosage Pt no. Mean change in total score [baseline] Response Remission
(mg/day) [mean at endpoint] MADRS HAM-D17 rate (%) rate (%)
Vs PL alone
Ninan et al.[39,63]a ESC 10–20 143 -6.4b/-13.3*c [30.4] 49**d 32*d
(8 wk) PL 151 -5.6b/-10.0c [30.5] 30d 21d
Wade et al.[40] ESC 10 188 -16.3**b [29.2] 55** 47**d
(8 wk) PL 189 -13.6b [28.7] 42 34d
Vs CIT and other SSRIs
Baldwin et al.[45] ESC 10 or 20e [13.9] 165 -17.16b,f [29.6] 67.9 56.4
g
(8 wk ) PAR 20 or 40 [26.3]e
158 -18.31b [29.7] 71.2 61.5
Burke et al.[35] ESC 10 118 -12.8**b [28.0] -10.2* [24.3] 50.0**
(8 wk) ESC 20 123 -13.9**b [28.9] -11.7** [25.8] 51.2**
*b *
CIT 40 125 -12.0 [29.2] -9.9 [25.9] 45.6**
PL 119 -9.4 [29.5]
b
-7.6 [25.8] 27.7
Lalit et al.[41] ESC 10 or 20e 69 -20b,d [26]h 90b 74b
(4 wk) CIT 20 or 40 e
74 -19 b,d
[25] h
86 b
65b
SER 100 or 150e,i 71 -21b,d [25]h 97b 77b
-
Lepola et al.[37] ESC 10 or 20e [14.0] 155 -15.0**b [29.0] 63.7 **
52.1-
(8 wk) e
CIT 20 or 40 [28.4] 159 -13.6 [29.2]
b
52.6 42.8
PL 154 -12.1b [28.7] 48.2 NR
Mao et al.[46] ESC 10 118 -20.9 [30.1] -15.8b,f [24.7] 80 46
(8 wk) FLU 20 113 -20.3 [31.2] -14.7b [24.1] 79 55
Moore et al.[42] -b --
ESC 20 138 -22.5 [36.3] 76.1 54.3
(8 wk) CIT 40 142 -20.1b [35.7] 61.3 43.0
Ou et al.[43] ESC 10–20 [13.9]e 115 -14.7b 72.2 60.9
(6 wk) CIT 20–40 [27.6]e 117 -13.8b 74.4 56.4
Ventura et al.[47] ESC 10 104 -19.1b [29.5] -16.9 [26.8]h 75 58
(8 wk) SER 50–200e [143.8] 107 -18.4b [29.0] -16.1 [26.8]h 70 58
Yevtushenko et al.[44] ESC 10 108 -28.70‡ #b [34.78] 95.4‡ # 89.8‡ #
(6 wk) CIT 10 106 -20.11b [35.40] 44.3 25.5
CIT 20 108 -25.19‡b [35.70] 83.3‡ 50.9‡
a Available as an abstract[39] and on the sponsor’s website.[63]
b Primary efficacy endpoint.
c 2 wk (primary endpoint)/8 wk values.
d Data estimated from figure.
e Dosages could be increased or decreased, depending on response and tolerability (in the final 2 wk only in one study[43]).
f Noninferiority demonstrated.
g Plus a 19 wk double-blind, maintenance period in pts with a significant clinical improvement. Results reported here are for the 8 wk duration.
Long-term results are presented in section 3.2.
h HAM-D24 (rather than HAM-D17) total score.
i 100 mg od or 150 mg/day (50 mg in the morning, 100 mg in the evening).
CIT = citalopram; FLU = fluoxetine; NR = not reported; PAR = paroxetine; SER = sertraline; * p £ 0.05, ** p < 0.01 vs PL; - p < 0.05, -- p < 0.01 vs
CIT; ‡ p < 0.001 vs CIT 10 mg/day; # p < 0.001 vs CIT 20 mg/day.

ª 2010 Adis Data Information BV. All rights reserved. CNS Drugs 2010; 24 (9)
778 Garnock-Jones & McCormack

Table IV. Efficacy of escitalopram (ESC) vs serotonin-noradrenaline (norepinephrine) reuptake inhibitors (SNRIs) or bupropion (BUP) in
patients (pts) with major depressive disorder. Short-term (8 wk), randomized, double-blind, multicentre studies in pts with moderate to severe
disease.[36,38,48-51] Drugs were given once daily (od), unless otherwise specified. Results are for the modified intent-to-treat population, using
last observation carried forward imputation, where stated.[36,38,48-51] See table II for definitions of efficacy parameters
Study Target dosage Pt no. Mean change in total score [baseline] Response Remission
(mg/day) [meana] MADRS HAM-D17 rate (%) rate (%)
Vs SNRIs
Asnis et al.[48,64]b ESC 20c 229 -22.4-
DUL 60 245 -20.6
Bielski et al.[49] ESC 20 97 -15.9d [30.7] -14.9 [28.6]e 58.8 41.2
VEN XR 225 98 -13.6d [30.0] -12.9 [27.4]e 48 36.7
Khan et al.[50] ESC 10 or 20 [13.0]f 136 -18.0-d [31.0] -11.1- [20.9] 68- 44
DUL 60 126 -15.9 [31.6]
d
-9.6 [21.2] 50 38
Montgomery et al.[51] ESC 10 or 20 [12.1]f 146 -18.16d,g [28.7] -12.52 [19.9] 77.4 69.9
VEN XR 75 or 150 [95.2]f 142 -18.93d [29.0] -12.83 [20.4] 79.6 69.7
Nierenberg et al.[38]h ESC 10 274 -7.22 [17.8] 41 32
DUL 60 273 -7.61* [17.6] 43* 37
PL 137 -5.97 [17.7] 32 27
Vs BUP
Clayton et al. [study 1][36] ESC 10 or 20f [13] 133 -14.2*d [23.3] 68** 49**
BUP 300 or 450f,i [323] 134 -13.2d [23.9] 61 40*
PL 130 -12.1d [23.3] 53 31
Clayton et al. [study 2][36] ESC 10 or 20f [13] 133 -12.9d [23.3] 62 42
BUP 300 or 450f,i [309] 129 -13.1d [23.2] 63 46
PL 126 -11.9d [23.3] 51 38
a Overall,[50] at endpoint[51] or unspecified.[36]
b Available as an abstract[48] and on the sponsor’s website.[64]
c Pts underwent single-blind treatment with ESC 10 mg/day for 2 wk, after which nonresponders (<50% improvement in MADRS total score)
were randomized.
d Primary efficacy endpoint.
e HAM-D24 (rather than HAM-D17) total score.
f Dosages could be increased or decreased, depending on response and tolerability.
g Noninferiority demonstrated.
h This study also had a double-blind, maintenance period of 6 mo duration. Results reported here are for the 8 wk duration. Long-term results
are presented in section 3.2.
i 300 mg od or 450 mg/day (300 mg in the morning, 150 mg in the afternoon).
DUL = duloxetine; PL = placebo; VEN XR = venlafaxine extended release; * p £ 0.05, ** p £ 0.01 vs PL; - p < 0.05 vs DUL.

citalopram 10 or 20 mg/day recipients, starting
at week 1 and continuing throughout the study
(between-group differences at endpoint -6.00
[escitalopram vs citalopram 10 mg/day] and -2.48
[escitalopram vs citalopram 20 mg/day]).[44]
The changes from baseline to endpoint in HAM-
D (primary endpoint in two trials[41,43])[35,41,43]
and CGI-S[35,37,41,42,44] scores and final CGI-I
scores[35,37,41,44] did not generally differ signif-
icantly between escitalopram and citalopram re-
cipients. In the study that included CGI-S and
CGI-I as co-primary endpoints,[41] mean change
in CGI-S score (-2.9 vs -2.7) and final mean
CGI-I score (1.3 vs 1.5) did not differ significantly
between escitalopram and citalopram recipients.
However, one study[44] found significantly (p < 0.001)
greater improvements in escitalopram than in
citalopram 10 and 20 mg recipients for CGI-S
(-2.60 vs -1.61 and -2.05) and CGI-I (1.58 vs
2.35 and 1.80).

ª 2010 Adis Data Information BV. All rights reserved. CNS Drugs 2010; 24 (9)
Escitalopram: A Review
Results were mixed for response and remission
rates (coprimary endpoints in one trial[41]).[35,37,41-44]
Escitalopram was associated with a significantly
higher response rate than citalopram (50–95% vs
44–86%) in three[37,42,44] of the six trials that
compared these two agents;[35,37,41-44] no signif-
icant difference between groups was observed in
the other trials[35,41,43] (table III). Of the five trials
in which remission rates were assessed, two[37,44]
showed a significantly higher remission rate among
escitalopram than among citalopram recipients
(52–90% vs 26–65%); again, no significant dif-
ference between groups was observed in the other
trials[41-43] (table III). A total of 58% of escitalo-
pram and 49% of citalopram recipients respond-
ed by week 2 in one study; 23% and 19% remitted
by week 2.[41]
A subgroup of patients with severe depression in
one study[44] demonstrated similar results to those
observed in the total study population. Significant
(p < 0.001) differences between escitalopram (n = 66)
and citalopram 10 (n = 65) or 20 (n = 78) mg/day
recipients in mean change from baseline in MADRS
total scores at endpoint were observed (between-
group differences -9.46 [escitalopram vs citalopram
10 mg/day] and -3.99 [escitalopram vs citalopram
20 mg/day]); significant (p < 0.001) between-group
differences were also observed for the MADRS core
depression subscale score in these patients.
3.1.3 Versus Other Selective Serotonin Reuptake
Inhibitors (SSRIs)
Escitalopram recipients and those receiving
the SSRIs paroxetine, sertraline or fluoxetine did
not differ significantly in mean change from base-
line to endpoint in MADRS total score (primary
endpoint in two studies[45,47]) [table III],[45-47] nor
were there any significant differences between
recipients of escitalopram and other SSRIs in
change from baseline to endpoint in HAM-D
total score[41,46,47] (primary endpoint in one
study,[46] coprimary endpoint in another study[41]),
change in CGI-S score[41,46,47] (coprimary endpoint
in one study[41]), CGI-I score[41,47] (coprimary end-
point in one study[41]), response rate[41,45-47] (co-
primary endpoint in one study[41]) or remission
rate[41,45-47] (coprimary endpoint in one study[41])
[table III]. Noninferiority of escitalopram to paro-
ª 2010 Adis Data Information BV. All rights reserved.
779
xetine[45] and fluoxetine[46] with regard to the primary
endpoints of change from baseline to endpoint in
MADRS total score (p > 0.05)[45] and HAM-D
total score (p > 0.05)[46] was demonstrated.
A total of 58% of escitalopram and 52% of
sertraline recipients had responded by week 2 in one
study; 23% and 17% had remitted by week 2.[41]
Week 2 response rates for escitalopram versus
fluoxetine recipients were 11% versus 12% (HAM-
D17 response) and 14% versus 17% (MADRS
response); corresponding week 2 remission rates
were 5% versus 4% (HAM-D17 remission) and
14% versus 16% (MADRS remission).[46] When
analysed by individual items on the HAM-D17,
escitalopram was associated with a significantly
(p < 0.05) greater response rate than fluoxetine
for ‘depressed mood’ and ‘work and interest’.[46]
A significantly greater number of recipients of
paroxetine were withdrawn (for any reason) from
the acute period (first 8 weeks) of one study than
escitalopram recipients (10 vs 2; p < 0.05).[45]
Improvements in health-related quality of life
(HR-QOL) did not differ significantly between
escitalopram and sertraline recipients; Q-LES-Q
short form scores (43.6 and 41.8 at baseline)
changed by +12.7 and +15.2 at endpoint, respec-
tively.[47] Improvements in HAM-A scores also
did not significantly differ between escitalopram
and sertraline.[47]
3.1.4 Versus Serotonin-Noradrenaline
(Norepinephrine) Reuptake Inhibitors (SNRIs)
Escitalopram was associated with a signif-
icantly (p < 0.05) greater decrease than duloxetine
from baseline to endpoint in MADRS total score
(primary endpoint in one study[50]) in two stud-
ies[48,50] (table IV). This significant difference
between treatment groups was first observed at
week 1 of double-blind treatment in one study,[48]
and, excluding week 6, was maintained through-
out treatment. The other study did not find a
significant difference between treatment groups
before week 8 (endpoint).[50]
With regard to the proportions of patients with
efficacy onset (a sustained 20% decrease from base-
line in HAM-D17 Maier subscale score) at week 2
(primary endpoint in one study[38]), duloxetine
was noninferior to escitalopram (42.6% vs 35.2%
CNS Drugs 2010; 24 (9)
780
of patients; treatment difference 7.4%; 95% CI
-1.3, 16.2).[38] This noninferiority outcome was
not affected when patient population or definition
of efficacy onset were changed.[38] A significantly
(p = 0.026) greater proportion of duloxetine than
escitalopram recipients showed efficacy onset at
endpoint, and duloxetine recipients reached onset
within a shorter median time than escitalopram
recipients (23 vs 41 days; p = 0.032).[38]
The mean change in HAM-D score from base-
line to endpoint was significantly greater in esci-
talopram recipients than in duloxetine recipients
in one study[50] when the HAM-D17 was used
(table IV), but not when the HAM-D24 was used.
The other study measuring this endpoint showed
no significant treatment difference (table IV).[38]
Where investigated, no significant differences were
found between escitalopram and duloxetine re-
cipients in changes on HAM-D subscales,[38,50]
with the exception of the sleep disturbance subscale
in one study,[50] where escitalopram recipients had
a significantly (p < 0.05) greater improvement than
duloxetine recipients.
Time to premature treatment discontinua-
tion (primary endpoint[48]) for any reason did not
differ significantly between escitalopram and
duloxetine recipients.[48] A total of 20.5% of es-
citalopram and 21.2% of duloxetine recipients
discontinued treatment prematurely in one
study[48] and 24%, 31% and 29% of escitalopram,
duloxetine and placebo recipients discontinued
treatment in another.[38] Significantly (p < 0.01)
more duloxetine than escitalopram recipients
discontinued in the third study (31% vs 13%).[50]
No significant differences were observed between
escitalopram and duloxetine in mean change from
baseline to endpoint in CGI-S,[38,50] CGI-I,[50]
Q-LES-Q[50] or HAM-A[50] scores, or in remission
rates[38,50] (table IV). The response rate was sig-
nificantly higher in escitalopram recipients than
in duloxetine recipients in one study[50] (table IV),
while no significant difference was observed for
this endpoint in the other study.[38]
No significant difference in mean change from
baseline to endpoint in MADRS score was ob-
served between escitalopram and venlafaxine
extended-release recipients (primary endpoint in
both studies comparing these treatments[49,51]), and
ª 2010 Adis Data Information BV. All rights reserved.
Garnock-Jones & McCormack
noninferiority of escitalopram to venlafaxine ex-
tended release was demonstrated[51] (table IV).[49,51]
In addition, there were no significant treatment
differences with regard to mean change from
baseline to endpoint in HAM-D (total[49,51] and
somatic subscale scores[49]),[49,51] HAM-A,[49]
Q-LES-Q,[49] CGI-S[49] or CGI-I scores,[49] nor in
response[49,51] or remission[49,51] rates (table IV).
In one study,[51] escitalopram recipients achieved
sustained (maintained until week 8) response and
sustained remission significantly (both p < 0.01)
faster than venlafaxine extended-release recipients.
3.1.5 Versus Other Antidepressants
Escitalopram treatment for £8 weeks did not
differ significantly from bupropion treatment in
patients with MDD.[36] There were no significant
differences between escitalopram and bupropion
recipients with regard to the primary efficacy
endpoint of mean change from baseline to end-
point in HAM-D total score (table IV), nor were
there significant differences between treatment
groups with regard to response or remission rates
(table IV), or in mean change in CGI-S score at
endpoint.[36]
3.1.6 In Elderly Patients
The efficacy of escitalopram treatment for 8[52] or
[53]
12 weeks did not differ significantly from that of
placebo in elderly patients with MDD,[52,53] and,
aside from the primary endpoint, did not differ
significantly from that of fluoxetine treatment[52]
(table V).
Escitalopram recipients did not differ signif-
icantly from placebo recipients with regard to
mean change from baseline to endpoint in MADRS
total score in either study (table V),[52,53] while the
improvements in MADRS total score were sig-
nificantly lower with fluoxetine than with escita-
lopram or placebo (table V).[52]
No significant differences were observed be-
tween escitalopram and placebo recipients[52,53]
or between escitalopram and fluoxetine[52] in mean
change from baseline to endpoint in HAM-D
total[53] or CGI-S[52,53] score or CGI-I score at
endpoint,[53] nor were there significant differ-
ences in response[52,53] or remission[52,53] rates.
CNS Drugs 2010; 24 (9)
Escitalopram: A Review
Table V. Efficacy of escitalopram (ESC) vs placebo (PL)[52,53] and fluoxetine (FLU)[52] in elderly (aged ‡60[53] or ‡65[52] years) patients (pts)
with moderate to severe major depressive disorder in short-term, randomized, double-blind, multicentre studies. Where stated, drugs were
given once daily.[53] Results are for the modified intent-to-treat population, using last observation carried forward imputation.[52,53] See table II
for definitions of efficacy parameters
Study (duration) Target dosage Pt no.
(mg/day) [overall mean]
Bose et al.[53] ESC 10 or 20a [14] 129
(12 wk) PL 134
Kasper et al.[52] ESC 10 170
(8 wk) FLU 20 164
PL 180
a Dosages could be increased to the maximum target dosage, depending on response.
b Primary endpoint.
c Estimated from a figure.
*
p < 0.05, ** p < 0.01 vs FLU.
3.2 Longer-Term Treatment
The efficacy of escitalopram in the longer-term
(‡24 weeks’) treatment of adults with MDD has
been investigated in several randomized, double-
blind, multicentre trials[45,54-60] and two noncom-
parative, multicentre trials.[61,62] These include
24-week efficacy comparisons between escitalo-
pram and paroxetine,[56] citalopram[55] or dulox-
etine[54] (section 3.2.1); prevention of recurrence
over 24–52 weeks in escitalopram responders or
remitters (section 3.2.2);[57-59] and extension stud-
ies (noncomparative[61,62] or comparison vs par-
oxetine[45] or duloxetine and placebo[60]) [section
3.2.3]. All studies were fully published;[45,54-62]
additional data from one study[57] were taken
from the sponsor’s website.[66] Patient numbers in
these trials ranged from 138 to 684.[45,54-62]
The primary efficacy endpoint of the long-term
studies was the change from baseline in MADRS
total score at endpoint (24[54-56] or 52[61] weeks) or
the time to relapse.[57-59] The other extension or
maintenance studies did not have primary end-
points for the long-term analyses.[45,60,62]
Where stated, results were calculated using the
mITT population,[45,54-62] using LOCF imputa-
tion[45,54-56,58,60-62] or observed cases.[45,59,62]
3.2.1 Long-Term Efficacy
Three well designed, 24-week trials investi-
gated the long-term efficacy of escitalopram
(table VI).[54-56]
ª 2010 Adis Data Information BV. All rights reserved.
781
Mean change in total score [baseline] Response rate Remission rate
MADRS HAM-D17 (%) (%)
-12.1b,c [29.4] -7.5 [20.3] 46 34
-10.4b,c [28.4] -7.1 [19.6] 38 29
-13.2**b,c [28.2] 46 40
-10.7b,c [28.5] 37 30
-13.4**b,c [28.6] 47 42*
Eligible patients were aged 18–65[54,55] or
18–75[56] years and had a DSM-IV[55] or DSM-
IV-TR[54,56] diagnosis of MDD (confirmed by the
Mini Neuropsychiatric Interview[54,56]),[54-56] with
moderate to severe depression ratings (MADRS
total score ‡26,[54] ‡30[56] or ‡22 and <40[55]).
Additional criteria included a CGI-S score ‡4[54]
and a current depressive episode of >2 weeks and
<1 year.[56]
At baseline, the mean age was 43–46 years[54-56]
and 69–74% of patients were female.[54-56] Where
stated, 66% of patients had recurrent illness[56]
and 50% of patients were severely (MADRS score
‡30) depressed.[55] Baseline characteristics were
similar between treatment groups.[54-56]
Overall, long-term treatment with escitalo-
pram compared favourably with other antide-
pressant drugs in the treatment of adults with
MDD (table VI).[54-56]
Treatment with escitalopram 10 mg/day for
24 weeks did not differ significantly from treatment
with citalopram 20 mg/day in the change from
baseline to week 24 in MADRS total score in
patients with moderate to severe MDD (primary
endpoint; table VI).[55] In addition, escitalopram
was found to be noninferior to citalopram treat-
ment, as the treatment difference in MADRS
total score change from baseline at week 8 had a
lower 95% CI limit of -0.95 (within the prespeci-
fied noninferiority limit of -3).[55]
With regard to other endpoints at 24 weeks,
escitalopram was associated with a significantly
CNS Drugs 2010; 24 (9)
782 Garnock-Jones & McCormack

Table VI. Efficacy of escitalopram (ESC) 10–20 mg/day for 24 weeks in patients (pts) with moderate to severe major depressive disorder.[54-56]
Comparison with paroxetine (PAR),[56] citalopram (CIT)[55] and duloxetine (DUL)[54] in randomized, double-blind, multicentre trials. Drugs were
given once daily.[54-56] Results are for the modified intent-to-treat populations, using last observation carried forward imputation.[54-56] The
primary endpoint was the mean change from baseline in MADRS total score.[54-56] See table II for definitions of efficacy parameters
Study Target dosage Pt no. Mean change in total score [baseline] Response rate Remission rate
(mg/day) MADRS HAM-D17 (%) (%)
Boulenger et al.[56] ESC 20 228 -25.2*a [35.2] -16.9** [24.7] 82.0 75.0*
PAR 40 223 -23.1 [34.8] -15.0 [24.3] 76.7 66.8
Colonna et al.[55] ESC 10 165 -21.5 [29.8] 80 76
CIT 20 174 -20.5 [29.8] 78 71
Wade et al.[54] ESC 20 141 -23.4a [32.5] -15.57 [22.7] 81.6 73.0
DUL 60 146 -21.7 [32.1] -14.23 [22.7] 76.7 69.9
a Noninferiority[54] and superiority[56] were demonstrated.
*
p < 0.05, ** p < 0.01 vs PAR.

(p < 0.05) greater improvement in CGI-S score
than citalopram (-2.49 vs -2.24), but there were no
significant between-treatment differences with re-
gard to response and remission rates (table VI).[55]
At week 8, the change from baseline in MADRS
total and CGI-S scores did not significantly differ
between escitalopram and citalopram recipients,
nor did remission rates; however, the response rate in
escitalopram recipients was significantly higher than
in citalopram recipients (63% vs 55%; p < 0.05).[55]
Escitalopram 20 mg/day treatment for 24 weeks
was more effective than paroxetine 40 mg/day in
patients with MDD.[56] The between-group dif-
ference in mean change from baseline in MADRS
total score at 24 weeks (primary endpoint) was
+2.12 in favour of escitalopram (95% CI 0.32,
3.92; p = 0.0105) [table VI].[56] Escitalopram also
had greater reductions in MADRS total score
than paroxetine at week 12 (treatment difference
2.00; 95% CI 0.32, 3.67; p = 0.0097) and at week
24 in severely depressed patients (treatment dif-
ference 3.45; 95% CI 0.51, 6.39; p = 0.0108).[56]
Moreover, escitalopram was associated with a
significantly greater improvement than paroxetine
in HAM-D17 total, HAM-D24 total (-22.5 vs
-20.0; p < 0.01) and CGI-S (-2.8 vs -2.6; p < 0.05)
scores, a significantly (p < 0.05) lower CGI-I
score (1.96 vs 2.19), and a significantly higher
remission rate at endpoint (table VI), as well as
a significantly (p < 0.01) greater improvement in
HAM-A score.[56] No significant difference in
response rate was observed between escitalopram
and paroxetine at endpoint (table VI).[56]
Twenty-four weeks’ treatment with escitalopram
20 mg/day was noninferior to duloxetine 60 mg/day
in patients with MDD.[54] The between-group dif-
ference in mean change from baseline in MADRS
total score (primary endpoint) in the mITT po-
pulation was 1.69 (95% CI –0.30, 3.78; p = 0.055),
which was within the prespecified noninferiority
one-sided CI margin of 2.5 (table VI).[54]
No significant differences between escitalopram
and duloxetine recipients were observed in mean
change from baseline in HAM-D total, HAM-A
or CGI-S score, CGI-I score, or response or remis-
sion rates at endpoint.[54] HR-QOL, measured on
the SF-36, also did not differ significantly between
treatment groups.[54]
At week 8, the mean change from baseline in
MADRS total score was -19.5 versus -17.4 in
escitalopram versus duloxetine recipients (p < 0.05),
with noninferiority demonstrated.[54] Response
rates at week 8 were 68.8% versus 57.5%, re-
spectively (p < 0.05); however, remission rates did
not significantly differ between groups. Escitalo-
pram was associated with a significantly greater
CGI-I score at week 8 than duloxetine (p < 0.05).
No significant differences between groups were
demonstrated in mean change from baseline in
HAM-D total, HAM-A or CGI-S score.[54]
3.2.2 Prevention of Relapse or Recurrence
Three studies investigated the prevention of re-
currence or relapse of MDD over a 24- to 52-week,
double-blind, maintenance period in adult patients

ª 2010 Adis Data Information BV. All rights reserved. CNS Drugs 2010; 24 (9)
Escitalopram: A Review 783

who had responded to previous escitalopram treat-
ment (table VII).[57-59]
Eligible patients in two studies had partici-
pated (and, in one study, responded to treatment
[MADRS score £12][59]) in previous short-term
antidepressant trials (treatments in these trials in-
cluded citalopram,[59] sertraline,[59] paroxetine,[59]
fluoxetine,[59] escitalopram[57] or placebo[57,58]). Pa-
tients entered the double-blind maintenance phase
of the trial with MADRS scores £12 (defined as
response[57,59] or remission[58]) following an open-
label, lead-in phase of treatment with escitalo-
pram 10–20 mg/day for 8,[57] 12[58] or 16[59] weeks.
At the beginning of the double-blind mainten-
ance phase (baseline), the mean age was 43 years
(adult studies)[57,59] or 73 years (elderly patients),[58]
and 61–79% of patients were female.[57-59] Patients
had a mean of 5.2 previous depressive episodes[59]
and 69.3% of patients had recurrent disease.[57]
Baseline characteristics were similar between treat-
ment groups.[57-59]
Escitalopram 10 or 20 mg/day maintenance
treatment for 24–52 weeks was effective in the pre-
vention of recurrence or relapse in adults (including
elderly patients[58]) with MDD who had responded
to previous escitalopram treatment.[57-59] The time
to recurrence or relapse (primary endpoint) was sig-
nificantly (p < 0.05) longer in escitalopram than in
placebo recipients[57-59] (table VII[59]).
The cumulative rate of recurrence or relapse
was significantly (p < 0.05) higher among placebo
than among escitalopram recipients (table
VII).[57-59] Where reported, the hazard ratio for
the difference between escitalopram and placebo
treatment remained significant (p < 0.001) after
censoring all recurrence or relapse events that
occurred within the first 7[58] or 14[58,59] days of
the double-blind treatment. Time to recurrence
or relapse was not affected by factors including
age, sex or depression history.[57,58]
Changes in scores on depression rating scales
either showed no significant difference between esci-
talopram and placebo recipients,[59] or there was a
significantly greater improvement[57] or significantly
less deterioration[58] among escitalopram recipients
than among placebo recipients[57,58] (table VII).

Table VII. Efficacy of escitalopram (ESC) 10–20 mg/day for the prevention of relapse[57,58] or recurrence[59] in adult patients (pts) with
moderate to severe major depressive disorder who had responded to previous ESC treatment.[57-59] Following an open-label, lead-in phase of
treatment with ESC 10–20 mg/day for 8,[57] 12[58] or 16[59] weeks, pts entered the long-term, randomized, double-blind, placebo (PL)-
controlled, multicentre trials.[57-59] The primary efficacy parameter was time to relapse.[57-59] Where stated, results are for the modified intent-
to-treat populations,[57-59] using last observation carried forward imputation[58] or observed cases.[59] See table II for definitions of efficacy
parameters
Study Treatment Pt no. Time to relapse[57,58]/recurrence[59] Mean change in score from
(double-blind period (mg/day) [overall mean] daysa cumulative HRb (95% CI) baseline [baseline]
duration) relapse/ MADRS totalb HAM-D24 total
recurrence
rate (%)
Kornstein et al.[59] ESC 10 or 20 [15.5]c 73 252 [357] 27 0.26 (0.13, 0.52)** +0.1 [4.7] -0.5 [5.2]
(52 wk) PL 65 130 [58]a
65 -0.3 [4.9] -0.2 [5.2]
Rapaport et al.[57,66]d ESC 10 or 20c 181 188 26 0.56 (0.35, 0.89)* -1.4* [7.2] -1.6* [7.7]
(36 wk) PL 93 56 40 +0.7 [6.2] +0.8 [6.6]
In elderly pts
Gorwood et al.[58] ESC 10 or 20c 152 NR** 9*** 4.44 (2.41, 8.17)** +0.86** [5.1]
(24 wk) PL e
153 NR 33 +6.62 [5.1]
a Mean [median], where stated.[59]
b Likelihood of relapse or recurrence in ESC vs PL[57,59] or PL vs ESC recipients.[58]
c Pts received a fixed dose equal to that they were receiving at the end of the open-label lead-in period.
d Additional data were obtained from the sponsor’s website.[66]
e Pts who had previously received ESC 20 mg/day received ESC 10 mg/day for the first week of PL treatment.
HR = hazard ratio; NR = not reported; * p £ 0.05, ** p < 0.001 vs PL.

ª 2010 Adis Data Information BV. All rights reserved. CNS Drugs 2010; 24 (9)
784
3.2.3 Extension or Maintenance Studies
Results from several extension or maintenance
studies following on from shorter-term trials (see
sections 3.1.1–3.1.4 and 3.1.6)[37,38,40,45,52] have
been reported.[45,60-62]
These studies continued treatment for 19,[45]
24 or 52[61,62] weeks at fixed[45] or flexible[60-62]
[60]
dosages of escitalopram 10–20 mg/day. Two studies
were noncomparative,[61,62] while the others com-
pared escitalopram with paroxetine 20–40 mg/day[45]
or duloxetine 60–120 mg/day,[60] in a double-
blind manner.
Patients with MDD receiving escitalopram 10
or 20 mg/day or paroxetine 20 or 40 mg/day treat-
ment over 27 weeks did not significantly differ
between treatment groups with regard to change
from baseline (prior to the acute [original study]
treatment period) in MADRS total score (score
at endpoint 8.0 vs 9.4; baseline 29.6 vs 29.7).[45]
In the two noncomparative trials, escitalopram
10–20 mg/day over 52 weeks was associated with
a mean MADRS total score (primary endpoint in
one study[61]) at endpoint of 7.2[61] and 8.5[62] in
adult[61] and elderly[62] patients (baseline [prior to
the extension period] 14.2[61] and 13.4[62]).
Moreover, after 8 months, there was no signif-
icant difference between escitalopram 10–20 mg/day
and duloxetine 60–120 mg/day in mean change
from baseline in HAM-D17 total score.[60] From
baseline (prior to the acute [original study] treat-
ment period) scores of 17.8, 17.6 and 17.7 in
patients receiving escitalopram, duloxetine and
placebo, respectively, scores changed by -10.91,
-10.55 and -8.06.[60] No significant difference
was also observed between escitalopram and du-
loxetine recipients in mean change from baseline
in HAM-D17 Maier subscale score.
Patients in one study who were severely de-
pressed and received escitalopram demonstrated
a significantly (p < 0.05) greater decline in total
MADRS score at 27 weeks than those receiving
paroxetine (-23.6 vs -20.2); the mean change in
MADRS score from baseline did not differ between
treatment groups in moderately ill patients.[45]
In addition, no significant differences were
reported between escitalopram and paroxetine[45]
or duloxetine[60] recipients with regard to mean
change in HAM-A[60] or CGI-S scores,[60] response
ª 2010 Adis Data Information BV. All rights reserved.
Garnock-Jones & McCormack
rates[45] or remission rates[45,60] at the end of the
maintenance period.
4. Tolerability
Tolerability data for escitalopram in adults
with MDD are available from the US prescribing
information,[11] the EU SPC,[12] and clinical trials
presented in section 3,[35-62] supplemented by ad-
ditional, fully published data.[67-76]
4.1 General Tolerability
Escitalopram 10–20 mg/day was generally well
tolerated in patients with MDD.[11,12,35-62] The
most common adverse events with escitalopram
are shown in figure 1, and include nausea, ejacu-
lation disorder (section 4.3), insomnia, diarrhoea,
somnolence, dry mouth, rhinitis, fatigue, influ-
enza-like symptoms, dizziness and increased
sweating.[11]
In a pooled analysis of two fixed-dose trials,
the overall incidences of adverse events among
escitalopram 10 and 20 mg/day versus placebo
recipients were 66% and 86% versus 61%.[11] No
evidence of dose dependency was found in a
pooled analysis of several trials in patients with
MDD or anxiety disorders.[67]
Where stated, the majority of adverse events
reported in patients receiving escitalopram in
clinical trials were of mild to moderate sever-
ity[35,37,40,41,46,52,58,61,62] and generally transient
in nature.[12,40,46,61,62] Serious adverse events oc-
curred in 0–1.1% of escitalopram recipients in
short-term studies.[38,41,43,44,47,50,63] No clinically
significant differences between escitalopram and
placebo were found in vital sign changes, weight
changes or ECG changes.[11]
In placebo-controlled trials, overall, 6% of 715
escitalopram recipients and 2% of 592 placebo
recipients discontinued treatment as a result of
adverse events.[11] Discontinuation rates did not
significantly differ between placebo (3%) and es-
citalopram 10 mg/day (4%) recipients, but esci-
talopram 20 mg/day recipients had a significantly
higher discontinuation rate (10%) than both (p-value
not reported).[11] The most common adverse events
leading to discontinuation were nausea (2% of
CNS Drugs 2010; 24 (9)
Escitalopram: A Review
Nausea
Ejaculation disorder1 ϕ
Insomnia
Diarrhoea
Somnolence
Dry mouth
Rhinitis
Fatigue
Influenza-like symptoms
Dizziness
Increased sweating
0 5
Fig. 1. Tolerability of escitalopram 10–20 mg/day (ESC) in patients with major depressive disorder in a pooled analysis of placebo (PL)-
controlled trials.[11] Treatment-emergent adverse events occurring in ‡5% of ESC recipients and with a higher incidence than among PL
recipients. 1 Incidence in males only (225 ESC and 188 PL recipients). j indicates occurred in <1% of patients.
escitalopram recipients) and ejaculation disorder
(2% of male escitalopram recipients).[11]
When investigated in a larger pooled ana-
lysis,[67] involving patients with MDD or anxiety
disorders, the tolerability profile of escitalopram
(n = 2740) versus placebo (n = 2199) was generally
similar to that observed in patients with MDD.
The overall incidence of adverse events (72.7% vs
63.1%) and the rate of treatment withdrawal as a
result of adverse events (7.3% vs 2.8%) were sig-
nificantly (p < 0.001) higher among escitalopram
than placebo recipients in this analysis.[67]
The general tolerability profile of escitalopram
was generally similar to that of other SSRIs[35,37,41-48]
and bupropion.[36] Escitalopram and citalopram
were significantly different with regard to the over-
all rate of adverse events in one study (6.5% for
escitalopram 10 mg/day vs 15.1% for citalopram
10 mg/day and 17.6% for citalopram 20 mg/day;
both p < 0.05).[44] No significant differences be-
tween escitalopram and bupropion in the incidence
of general adverse events were reported.[36]
Significant tolerability differences between es-
citalopram and SNRIs were more common.[38,49-51]
Rates of dry mouth (10.9% vs 21.6%),[38] insomnia
ª 2010 Adis Data Information BV. All rights reserved.
785
ESC (n = 715)
PL (n = 592)
10 15 20
Patients (%)
(9% vs 20%),[50] nausea (12.0% vs 23.8%),[38] vo-
miting (2.2% vs 7.3%)[38] and yawning (2.2% vs
5.5%)[38] were significantly (p < 0.05) lower with
escitalopram than with duloxetine, and rates of
nausea[49,51] (6.1% vs 24.0%[49]), constipation[51] and
increased sweating[51] were significantly (p < 0.05)
lower with escitalopram than with venlafaxine
extended release. Venlafaxine extended-release reci-
pients also demonstrated a significantly (p < 0.05)
greater increase in blood pressure,[49] pulse[49,51]
and ventricular heart rate[49] than those receiving
escitalopram.[49,51]
Withdrawal rates due to adverse events in
escitalopram recipients were generally similar
to those observed in patients receiving other
SSRIs[35,37,41-43,45,46] or bupropion,[36] and to SNRI
recipients in some studies (venlafaxine extend-
ed release[51] or duloxetine[38,48]), but not others,
specifically versus venlafaxine extended release
(4.1% of escitalopram recipients vs 16.0% of
venlafaxine recipients; p < 0.01)[49] and duloxetine
(2% of escitalopram recipients vs 13% of dulox-
etine recipients; p < 0.01).[50]
When investigated in a large pooled analysis,
involving patients with MDD or anxiety disorders,
CNS Drugs 2010; 24 (9)
786
no significant differences in the incidence of any
adverse events between escitalopram and citalo-
pram or fluoxetine were found, and the only signi-
ficant (p < 0.01) difference between escitalopram
and sertraline recipients was an increased inci-
dence of diarrhoea in sertraline versus escitalo-
pram recipients.[67] Escitalopram was associated
with a significantly (p < 0.05) lower incidence of
sexual dysfunction, dry mouth, and adverse event-
related withdrawals and a significantly (p < 0.01)
higher rate of headache than paroxetine. Escitalo-
pram was associated with a significantly (p < 0.01)
lower rate of nausea and adverse event-related with-
drawals than venlafaxine extended release.[67]
Long-term treatment (24–52 weeks) with esci-
talopram was generally well tolerated in adults
with MDD, with a similar tolerability profile to
that observed in shorter-term treatment studies.
In long-term studies, the treatment withdrawal
rate in escitalopram recipients as a result of adverse
events was 4–12%;[54-57,59-61] a rate that was signif-
icantly (p < 0.05) lower than that for paroxetine
recipients in one study (16%)[56] and duloxetine
recipients in another study (17%).[54] The events
leading to escitalopram treatment withdrawal in-
cluded nausea,[54-56,61] agitation,[54] headache,[56]
insomnia,[54,56] erectile dysfunction,[60] hyperten-
sion,[60] delayed ejaculation,[60] decreased libi-
do,[60,61] weight increase,[61] suicide attempt,[55,61]
aggravated depression[61] and palpitations.[60]
In general, escitalopram treatment (includ-
ing that over the long term[58,62]) in elderly pa-
tients had a similar tolerability profile to that of
adults.[11,52,53,58,62] Additionally, escitalopram and
fluoxetine had generally similar tolerability profiles
in this population.[52] As a class, SSRIs, including
escitalopram, have been associated with clinically
significant hyponatraemia in elderly patients.[11]
An acute overdose of escitalopram appeared
to be less toxic than an overdose of citalopram in
two retrospective reviews of overdose data from
421 versus 374[69] and 63 versus 316 patients,[68]
respectively. The incidence of seizures (1 vs 30 pa-
tients; p < 0.001) and tremors (13 vs 32; p < 0.001)
in one study[69] and seizures (1 vs 43; p = 0.0065)
in another study[68] was significantly lower among
recipients of an escitalopram overdose than a
citalopram overdose.
ª 2010 Adis Data Information BV. All rights reserved.
Garnock-Jones & McCormack
4.2 Suicidality
There is a black box warning in the US pre-
scribing information regarding an increased risk
of suicidal thinking and behaviour in paediatric
and young adult patients receiving antidepressant
drugs.[11] As a result of the potential risk of sui-
cidality, patients receiving antidepressants should
be monitored closely (especially patients with a
history of suicidality[12])[11,12] particularly during
the first few months of treatment.[11]
Pharmacovigilance data for >12 million patients
with MDD and/or anxiety demonstrate a suicide
rate of 1.8 per million patients treated with esci-
talopram, a rate which is approximately equiva-
lent to that for citalopram recipients (2 per million
prescriptions), and significantly (p-value not sta-
ted) lower than those for TCAs and related anti-
depressants (12 per million prescriptions) or
MAOIs (14 per million prescriptions).[70]
As a class, SSRIs are potentially associated
with non-fatal self-harm but not suicide or suici-
dal thoughts, according to results from a detailed
meta-analysis of data from placebo-controlled
trials of SSRIs in >40 000 patients.[71] The odds
ratio for non-fatal self-harm was 1.57 (95% CI
0.99, 2.55), for suicide was 0.85 (95% CI 0.20,
3.40) and for suicidal thoughts was 0.77 (0.37,
1.55). However, neither a protective nor a detri-
mental effect could be excluded.[71]
This meta-analysis[71] also indicated that esci-
talopram (2648 recipients in 34 trials), versus
placebo (2088 recipients), was associated with a
risk estimate for suicide of 0.79 (95% CI 0.05,
12.61), non-fatal self-harm of 4.74 (95% CI 0.57,
39.40) and suicidal thoughts of 0.39 (95% CI 0.04,
4.35).[71]
In another large meta-analysis of 12 placebo-
controlled trials specifically investigating escita-
lopram in patients with MDD or anxiety disorders
(2277 escitalopram and 1814 placebo recipients),[70]
no significant differences were found between
escitalopram and placebo in the incidence of
suicide, non-fatal self-harm or suicidal thoughts,
either during the first 2 weeks of treatment (0% vs
0%, 0.1% vs 0.1% and 0.04% vs 0%, respectively)
or during the full treatment period (£24 weeks;
0% vs 0.1%, 0.2% vs 0.1% and 0.04% vs 0.1%,
CNS Drugs 2010; 24 (9)
Escitalopram: A Review
respectively). In two relapse-prevention trials
(371 escitalopram and 274 placebo recipients), no
suicides or suicidal thoughts were reported in
either group, and non-fatal self-harm occurred in
0.3% of the escitalopram group over the whole
treatment period of £36 weeks compared with 0%
of placebo recipients.[70] Moreover, in patients
with MDD (1021 escitalopram and 918 placebo
recipients), the improvement from baseline in
mean score on item 10 (suicidal thoughts) of the
MADRS was significantly greater among escita-
lopram than among placebo recipients at all
timepoints over 8 weeks (p < 0.05).[70] However,
the population of patients involved in these clin-
ical trials was generally selected for their lack of
suicidal ideation (section 3), which may factor
into these results.
4.3 Sexual Dysfunction
Both depression and SSRIs (including escita-
lopram) have been associated with male and fe-
male sexual dysfunction (changes in sexual desire,
sexual performance and sexual satisfaction).[11]
While some data exist on the incidence of sexual
dysfunction associated with SSRIs, reliable esti-
mates are unlikely for various reasons, including
discomfort with discussion of such events, or the
general depression of libido associated with de-
pression itself.
In placebo-controlled trials, 407 escitalopram
recipients and 383 placebo recipients were male;
sexual adverse events in males included ejacula-
tion disorder (mainly ejaculatory delay) [12% and
1%, respectively], decreased libido (6% and 2%)
and impotence (2% and <1%).[11] Additionally,
priapism has been reported with all SSRIs.[11] In
the placebo-controlled trials, the sexual adverse
events occurring in female patients (737 escitalo-
pram and 636 placebo recipients) included de-
creased libido (3% and 1%) and anorgasmia (3%
and <1%).[11]
Two analyses investigated the difference be-
tween escitalopram and other antidepressants
(bupropion[36] and duloxetine[72]) in the incidence
of sexual dysfunction. Escitalopram recipients
(30% of 281 patients) had a significantly greater
incidence of orgasm dysfunction (primary end-
ª 2010 Adis Data Information BV. All rights reserved.
787
point) and worsened sexual functioning at 8 weeks
than bupropion recipients (15% of 276 patients;
p < 0.05) and placebo recipients (9% of 273 pa-
tients; p £ 0.001) in the pooled data from two
studies (as well as in the individual trials).[36]
Worsened sexual functioning occurred in 36%,
20% and 15%, respectively.[36]
Moreover, in patients with no sexual dys-
function at baseline (n = 39, 51 and 24 for escita-
lopram, duloxetine and placebo recipients), esci-
talopram was also associated with a significantly
(p £ 0.05) higher incidence of treatment-emergent
global sexual dysfunction on the Changes in Sexual
Functioning Questionnaire than duloxetine at 4
and 12 weeks, but not at any other timepoint over
the 8-month treatment period, and placebo at
weeks 4 and 8 but not any other timepoint.[72]
Conversely, a study investigating escitalopram
(n = 165) versus paroxetine (n = 156) over 27 weeks,
including the 67% and 70% of patients with sexual
dysfunction at baseline, found no significant differ-
ence between treatment groups in the proportions
of patients with sexual dysfunction at weeks 8 (61%
and 64%) and 27 (57% and 58%).[45] Moreover, in
a small, retrospective analysis, 32 of 47 patients
(68.1%) with SSRI- or SNRI-associated sexual
dysfunction improved to a mild or marked degree
when treatment was switched to escitalopram.[73]
In a large, pooled analysis involving patients
with MDD or anxiety disorders, the incidence of
sexual function-related adverse events was sig-
nificantly higher in escitalopram (n = 2740) than
placebo (n = 2199) recipients (10.3% vs 2.1%;
p < 0.001), did not significantly differ in escitalo-
pram (n = 827) versus citalopram (n = 709) recipi-
ents (7.7% vs 6.6%), and was significantly lower
in escitalopram (n = 1288) than paroxetine (n = 870)
recipients (8.9% vs 14.4%; p < 0.001).[67]
4.4 Treatment Discontinuation-Emergent
Adverse Events
Adverse events associated with the disconti-
nuation of SSRIs are common, especially when
discontinuation is abrupt; patients should there-
fore be monitored for symptoms when disconti-
nuing escitalopram treatment.[11,12] Symptoms may
include dysphoric mood, irritability, agitation,
CNS Drugs 2010; 24 (9)
788
dizziness, sensory disturbance, anxiety, confu-
sion, headache, lethargy, emotional lability, sleep
disturbance, nausea, vomiting, tremor, sweating,
diarrhoea, palpitations and hypomania,[11,12] and
are generally mild to moderate,[12] although some
may be severe.[11,12] Discontinuation adverse events
are generally self-limiting[11,12] and are usually re-
solved within 2 weeks;[12] however, they may be pro-
longed in some patients (2–3 months or longer).[12]
While escitalopram appears to be associated
with discontinuation adverse events,[12] data sug-
gest that it may be associated with fewer events
than other antidepressants.[45,51] In clinical trials,
25% of escitalopram and 15% of placebo recipients
reported adverse events upon treatment disconti-
nuation.[12] However, escitalopram was associated
with significantly (p < 0.01) fewer discontinuation-
emergent adverse events than venlafaxine ex-
tended release following 8 weeks’ treatment[51]
and paroxetine following 27 weeks’ treatment.[45]
4.5 Post-Marketing Surveillance Studies
Post-marketing studies in patients with MDD
(including patients without restrictions as to co-
morbid disorders and concomitant treatments),
each involving >5000 recipients of escitalopram
10–20 mg/day (total of >22 000 patients), were
conducted in the US (n = 5453),[74] Germany
(n = 11 760)[75] and Greece (n = 5175)[76] over treat-
ment periods of 8 weeks[74,75] or 3 months.[76]
Escitalopram was generally well tolerated in these
studies; the overall rate of adverse events was
6.7–28.1%.[74-76] The most common adverse
events in one study[74] (incidence >2% of the
population) included nausea (4.6% of patients),
headache (3.4%), ejaculation disorder (2.5% of
men), diarrhoea (2.3%), insomnia (2.4%), som-
nolence (2.3%) and fatigue (2.1%); in another
study,[75] the incidence of specific adverse events
did not exceed 2%. Treatment discontinuation as
a result of adverse events occurred in 1.6%[76] and
8.7%[74] of escitalopram recipients, where stated.
The majority of adverse events were of mild to
moderate severity;[74,75] serious adverse events
occurred in 0.02–1.2% of patients.[74-76] In one
study, one death was considered probably related
to escitalopram treatment (a fatal suicide).[75]
ª 2010 Adis Data Information BV. All rights reserved.
Garnock-Jones & McCormack
5. Pharmacoeconomic Considerations
Due to a large amount of data on the cost ef-
fectiveness of escitalopram, details in this section
are limited to an overview of well designed, fully
published trials that incorporated cost data from
2004 or later and outcomes data from key head-
to-head clinical trials.[77-83]
Escitalopram dominated (i.e. cost less and was
more effective than) citalopram[82] or duloxetine,[83]
regardless of cost per efficacy or tolerability para-
meter (remission,[82] MADRS score,[82] Sheehan
Disability Scale score[83] or sick leave[83]) in two
prospective pharmacoeconomic studies in patients
with MDD. These studies[82,83] assessed the cost
effectiveness of escitalopram 20 mg/day versus
citalopram 40 mg/day[82] or duloxetine 60 mg/day[83]
alongside short-[42] and longer-term,[54] random-
ized, double-blind, efficacy trials (section 3) in pa-
tients with MDD. The analyses were conducted
from the French National Health Insurance (direct
medical costs)[82] or UK societal (direct medical
and indirect costs)[83] perspective, covered the treat-
ment periods of 8[82] or 24[83] weeks, and incor-
porated cost data from 2004[82] or 2006.[83]
Escitalopram dominated citalopram,[79] fluo-
xetine,[77] venlafaxine extended release[77,78,80] and
fluvoxamine[80] or was considered equivalent to
venlafaxine extended release[79] in modelled ana-
lyses of the incremental cost per successfully
treated patient with MDD, conducted in a num-
ber of countries from a healthcare payer and/or
societal perspective (table VIII).[77-81]
In a study investigating the incremental cost per
quality-adjusted life-year gained with escitalopram
10–20 mg/day versus sertraline 50–200 mg/day in
patients with MDD, escitalopram dominated
sertraline.[81] This study was based on a decision
analytic model and was from a US managed care
organisation perspective (direct medical costs),[81]
using outcomes data from a randomized, double-
blind trial[47] and country-specific costs from
2005.[81]
Sensitivity analyses were performed in most
cases.[77,79-83] Results remained generally robust
to changes in plausible key model assump-
tions;[77,79-81,83] one study found that using generic-
price citalopram instead of brand-price citalopram
CNS Drugs 2010; 24 (9)
Escitalopram: A Review 789

resulted in escitalopram remaining more favour-
able, but not significantly so.[82]
Pharmacoeconomic analyses of escitalopram,
in common with all pharmacoeconomic analyses,
are subject to a number of limitations. Pharma-
coeconomic analyses based on clinical trials ex-
trapolate the results of such trials to the general
population; however, patient populations, rates
of compliance, and major outcomes in clinical
trials may differ from those observed in real-life
practice. Modelled analyses rely on a number of
assumptions and use data from a variety of
sources. Results of pharmacoeconomic analyses
may not be applicable to other geographical re-
gions because of differences in healthcare sys-
tems, medical practice, and unit costs.
6. Dosage and Administration
Escitalopram is approved for the acute and
maintenance treatment of MDD as well as for
GAD in the US[11] and for treatment of major
depressive episodes as well as GAD, PD, SAD
and OCD in the EU.[12] Dosage of oral escitalo-
pram should be initiated at 10 mg/day in patients
with MDD,[11,12] taken once daily with or with-
out food.[12] This dosage can be increased to
20 mg/day, depending on patient response,[11,12]
after a minimum of 1 week’s treatment.[11] Several
months of treatment with escitalopram are gen-
erally required past the initial response to the
acute episode;[11,12] the EU SPC specifies that a
treatment period of 2–4 weeks is required for
response and that once response is obtained,
further treatment for ‡6 months is needed for
longer lasting results.[12] The safety of dosages
exceeding 20 mg/day has not been demonstra-
ted.[12] Escitalopram is available as tablets[11,12]
or an oral solution.[11,33]
According to the US prescribing information,
elderly patients and those with hepatic impair-
ment should receive an escitalopram dosage of
10 mg/day (section 2.2).[11] The EU SPC specifies
that these patients and those known to be poor
metabolizers of CYP2C19 should receive half the
recommended dose (initial dosage of 5 mg/day,
maximum dosage of 10 mg/day), with upward
dosage titration in poor metabolizers and patients
with hepatic impairment only occurring after
2 weeks of treatment with the lower dosage (sec-
tion 2.2).[12] Dosage adjustment of escitalopram
is not necessary in patients with mild to moderate
renal impairment, but it should be administered
with caution in patients with severe renal impair-
ment (creatinine clearance <30 mL/min [1.8 L/h][12])
[section 2.2].[11,12]

Table VIII. Modelled cost-effectiveness analyses comparing escitalopram (ESC) with other antidepressant drugs in patients (pts) with major
depressive disorder. Studies were conducted from the healthcare provider (direct medical costs)[77-79] and/or societal (direct and indirect
costs)[77,79,80] perspective, using a 10-week[78] or 6-month[77,79,80] time horizon and based on a decision analytic model[77,79,80] or a Markov
model with 2-week cycles and three disease states (responders [‡50% improvement], partial responders [25–50% improvement] and non-
responders [<25% improvement]).[78] Efficacy data were derived from randomized head-to-head clinical trials; cost values were derived from
country-specific data and literature[77-80]
Study Country (year of Perspective Comparators (mg/day) Incremental cost per
costing) successfully treateda pt (ESC vs
comparator)
Kongsakon and Thailand (2007) Healthcare provider; ESC 10 vs FLU 20; Dominated FLU and VEN XR
Bunchapattanasakda[77] societal ESC 10 vs VEN XR 75 (both perspectives)
Kulp et al.[78] Germany (2004) Outpatient care ESC 10 vs VEN XR 75 Dominated VEN XR
Sørensen et al.[79] Denmark (2004) Health services; ESC 10–20 vs CITb 20–40; Dominated CIT;
societal ESC 10–20 vs VEN XR 75–150 Considered equivalent to
VEN XR (both perspectives)
Xie et al.[80] Singapore (2007) Societal ESC 10–20 vs VEN XR 75–150; Dominated VEN XR and FLV
ESC 10–20 vs FLV 100–200
a Defined as in remission[77,79,80] or responder.[78]
b Generic formulation.
CIT = citalopram; FLU = fluoxetine; FLV = fluvoxamine; QALY = quality-adjusted life-year; remission = Montgomery-Åsberg Depression
Rating Scale total score £12[77,80] (where defined); VEN XR = venlafaxine extended release.

ª 2010 Adis Data Information BV. All rights reserved. CNS Drugs 2010; 24 (9)
790
The US prescribing information contains a
black box warning regarding an increased risk of
suicidal thinking and behaviour in paediatric and
young adult patients receiving antidepressant
drugs (section 4.2).[11]
As discontinuation symptoms have been re-
ported with escitalopram (as with other SSRIs
and SNRIs), the dosage should be gradually re-
duced rather than an abrupt treatment cessation,
and patients should be monitored for symptoms
while stopping treatment.[11,12] If switching treat-
ment between escitalopram and a MAOI, a mini-
mum of 14 days should elapse between treatment
regimens.[11]
Local prescribing information should be con-
sulted for contraindications, precautions and warn-
ings, drug interactions, dosage modifications and
patient monitoring requirements.
7. Place of Escitalopram in the
Management of Major Depressive
Disorder in Adults
In the US during the 1980s, the predominant
antidepressant class used to treat MDD was the
TCAs;[84] however, following the US release of
the first SSRI (fluoxetine) in 1988, the rate of
SSRI prescriptions quickly grew until the class
dominated the market from the early 1990s on,[84]
remaining the most commonly prescribed anti-
depressants worldwide into this decade.[84-89] This
is consistent with recommendations in current
treatment guidelines, where SSRIs are considered
among the first-line treatments for patients with
MDD.[5-7]
While different SSRIs all have the same main
mechanism, namely the inhibition of serotonin
reuptake at the cellular synapse, they are in fact a
heterogeneous drug class with regard to second-
ary effects; these secondary properties may be the
cause of several differences in efficacy and toler-
ability observed between SSRIs, and may explain
why some patients respond better to one SSRI
than another.[90] Aside from having differing
affinities at other receptors (leading to differing
effects),[90] SSRIs also have differing affinities for
SERT, with escitalopram the most selective SSRI
with regard to SERT binding (section 2.1). The
ª 2010 Adis Data Information BV. All rights reserved.
Garnock-Jones & McCormack
differences between SSRIs may be a result of
different binding requirements for each SSRI to
SERT (for example, some may directly inhibit
binding, whereas others may alter binding through
an allosteric interaction).[91] Escitalopram binds
to the allosteric binding site on SERT as well as
the primary binding site; this appears to have a
stabilizing, self-potentiating effect (section 2.1).
As escitalopram has a much lower binding
affinity than other SSRIs for other receptors, the
risk of adverse events linked with antagonism of
these receptors (such as anticholinergic, sedative
and cardiovascular effects, observed with other
psychotropic drugs) is likely much lower.[11] Ad-
ditionally, the lack of the R-enantiomer of race-
mic citalopram appears beneficial, as R-citalopram
has been suggested to have an inhibitory effect on
the efficacy of escitalopram, presumably due to a
conformational protein change at the serotonin
transporter (section 2.1); this is reflected in the
clinical trials discussed in section 3.
Escitalopram was generally more effective
than placebo (section 3.1.1) and at least as effec-
tive as citalopram (section 3.1.2) in adult patients
with MDD in short-term, well designed trials;
however, the results of efficacy comparisons be-
tween escitalopram and placebo or citalopram
were occasionally inconsistent with regard to sig-
nificance in primary and secondary endpoints.
Escitalopram was also generally at least as effective
as other comparator drugs, including the SSRIs
fluoxetine, paroxetine and sertraline (section 3.1.3),
the SNRIs venlafaxine extended release and du-
loxetine (section 3.1.4), and the aminoketone
bupropion (section 3.1.5) in adult patients with
MDD in short-term, well designed trials. No well
designed trials comparing escitalopram with TCAs
have been published. Improvement in efficacy
endpoints, where reported, consistently occurred
within the first 1 or 2 weeks of treatment (section
3), confirming the rapid onset of action suggested
by preclinical studies (section 2.1). Additionally,
in almost all studies, well over half of escitalo-
pram recipients were responders, and remission
occurred in at least one-third (often more) of es-
citalopram recipients (section 3).
Maintenance therapy is commonly required to
prevent relapse and recurrence of depression.
CNS Drugs 2010; 24 (9)
Escitalopram: A Review
Long-term trials corroborated short-term results,
with escitalopram demonstrating greater efficacy
than placebo in relapse and recurrence preven-
tion (section 3.2.2). Additionally, escitalopram
was at least as effective as citalopram, paroxetine
and duloxetine in long-term comparative trials
(section 3.2).
Currently, there are no clear definitions of
dosage equivalence among new-generation anti-
depressants in the published literature; studies
comparing antidepressants may have inequalities
in dosing, affecting comparative efficacy. In ad-
dition, one study comparing escitalopram with
citalopram[44] used two different dosages of cita-
lopram. One was equivalent to the dosage of
escitalopram used, the other was lower; thus,
comparative efficacy was compromised for com-
parison between recipients of the lower dosage of
citalopram and recipients of escitalopram.[44]
Few trials reported HR-QOL data; where re-
ported, the improvement in HR-QOL was great-
er with escitalopram than with placebo treatment
(section 3.1.1), and no significant differences in
mean change in HR-QOL were found between
escitalopram and sertraline, duloxetine or venla-
faxine extended release (sections 3.1.3 and 3.1.4).
A pooled analysis of trials in patients with MDD
demonstrated a significant improvement in HR-
QOL with escitalopram treatment; remission in
these patients was correlated with ‘normal’ enjoy-
ment and satisfaction.[92] In addition, escitalopram
was found to be a cost-effective treatment for MDD
in several countries, dominating other SSRIs and
venlafaxine extended release (section 5).
While short-term treatment with escitalopram
in elderly patients did not demonstrate a signif-
icant difference from placebo treatment in effi-
cacy (section 3.1.6), longer-term trials have
shown efficacy in this population (sections 3.2.2
and 3.2.3), and results from one of the two short-
term trials should be interpreted with caution,
as it was deemed a ‘failed study’: neither active
treatment demonstrated efficacy compared with
placebo.[52] Thus, further investigation is re-
quired before conclusions can be made regarding
the efficacy of escitalopram in this population.
In postmarketing studies in patients with
MDD, involving >5000 escitalopram recipients
ª 2010 Adis Data Information BV. All rights reserved.
791
each (total of >22 000 patients),[74-76] results cor-
roborated those observed in randomized clinical
trials, with an improvement in overall health and
a decrease in depression measures. Moreover, in
further clinical trials, escitalopram remained ef-
fective when administered in patients with co-
morbid MDD and generalized anxiety disorder
(in elderly patients)[93] or alcohol dependence,[94]
and was safely and effectively used concomitantly
with bupropion[95] and repetitive transcranial mag-
netic stimulation,[96,97] as well as when used as a
continuation treatment following a switch from
intravenous citalopram[98] in patients with MDD.
While venlafaxine (an SNRI) appears to have
greater efficacy than SSRIs as a class in meta-
analyses, no significant difference between venla-
faxine and escitalopram has been demonstrated.[99]
Indeed, escitalopram performed at least as well as
competitors (including venlafaxine, duloxetine,
citalopram, bupropion, fluoxetine, paroxetine, and
sertraline) in meta-analyses (although sertraline was
suggested as the best initial choice[100]),[100,101] con-
sistent with the results from the randomized, con-
trolled trials discussed in section 3. However,
one meta-analysis found that, while escitalopram
was associated with greater reduction in depres-
sion symptoms and higher response rates than
citalopram, these differences generally did not
demonstrate compelling evidence for clinical re-
levance;[102] this is an interesting divergence from
the promising results observed in preclinical stud-
ies (section 2.1).
In patients with severe depression, escitalo-
pram, usually at the higher dosage, also compared
favourably with other antidepressant drugs in
pooled analyses.[103-106] Moreover, one of two pooled
analyses showed that escitalopram displayed
proportionally greater efficacy than citalopram
and placebo with increasing baseline disease
severity.[104]
Most adverse events in patients receiving es-
citalopram are mild to moderate and transient; in
general, escitalopram shares its most common
adverse events with other SSRIs, and is poten-
tially better tolerated than SNRIs such as dulox-
etine and venlafaxine extended release (section
4.1). Long-term escitalopram treatment has a sim-
ilar tolerability profile to that observed with
CNS Drugs 2010; 24 (9)
792
shorter-term escitalopram treatment (section 4.1).
Sexual dysfunction with escitalopram treatment
appeared to occur to a similar or lower extent to
that with paroxetine (another SSRI), to a similar
or greater extent to that with the SNRI dulox-
etine, and to a greater extent than that with with
the aminoketone bupropion (section 4.3), although,
in this study, bupropion did not differ signif-
icantly from placebo in efficacy (section 3.1.5).
Data suggest that escitalopram may be associated
with fewer discontinuation-related adverse events
than other antidepressants (section 4.4).
As a class, SSRIs may be associated with in-
creased risk of suicidality in younger patients.
Escitalopram recipients appear to have an equiv-
alent suicide rate to those receiving citalopram,
which is significantly lower than those receiving
TCAs or MAOIs (section 4.2). However, the ef-
fect of SSRIs on suicidality is still unclear, as
several different study types have produced dif-
fering conclusions, ranging from no effect or a
decline in suicide rates to increased rates of sui-
cidal ideation, self-harm or suicide,[107] and the
population of patients involved in clinical trials
was generally selected for their lack of suicidal
ideation (section 3). Nevertheless, close observation
with escitalopram treatment is recommended.[11,12]
Some studies have investigated the possibility of
genetic association with suicidal ideation[108,109] or
sexual dysfunction[110] upon treatment with citalo-
pram, and discovered that several gene markers were
significantly associated with these adverse events.
While caution is advised in the coadministra-
tion of escitalopram and CYP2D6 substrates as a
result of a modest increase in the CYP2D6 sub-
strate exposure, the potential interaction is likely
to be low; this is likely to be beneficial when the
treatment of psychotic MDD requires combina-
tion therapy with an antidepressant and CYP2D6-
metabolized antipsychotics.[9,10]
In conclusion, escitalopram is an effective and
well tolerated treatment for moderate to severe
MDD, with a rapid onset of antidepressant action
and a high affinity for the serotonin transporter
protein. It is at least as effective as citalopram and
other antidepressant drugs, and may have cost-
effectiveness advantages over other antidepres-
sants. It has a predictable tolerability profile with
ª 2010 Adis Data Information BV. All rights reserved.
Garnock-Jones & McCormack
generally mild to moderate and transient adverse
events, and a low propensity for drug interac-
tions. Escitalopram, like other SSRIs, is thus an
effective first-line option in the management of
patients with MDD.
Disclosure
The preparation of this review was not supported by any
external funding. During the peer review process, the manu-
facturer of the agent under review was offered an opportunity
to comment on this article. Changes resulting from comments
received were made on the basis of scientific and editorial
merit.
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