Escitalopram

I'm a pill that brings some cheer, For

those who struggle, I am near.
Depression's shadow I can tame,
With serotonin, I play the game.
What am I?
 Team 19 & Contribution
Sanchita Tiwari Introduction, Summary

Vidhi Makwana SAR Lead screening

Rishil Patel Pharmacokinetic (ADME)

Pari Patel Toxicity and Safety Assay

Aparna Krishna Clinical Trials (I,II,III)

Regulatory Affairs and its post marketing

Surbhi Bhingradiya surveillance
Introduction
 Interesting Fact
!!
Escitalopram is one of the most widely
prescribed antidepressants globally and
is considered a first-line treatment for
major depressive disorder and
generalized anxiety disorder.

Chu & Wadhwa et al., 2023

Escitalopram
 Escitalopram is the S-enantiomer
of racemic citalopram.

 Escitalopram belongs to a class

of antidepressants known
as selective serotonin reuptake
inhibitors(SSRIs).
Zhong et al., 2011a
 History
• The first drug in the SSRI class was Prozac
(Fluoxetine), which hit the United States market in
1987. Prozac was FDA approved in December
29,1987. It is manufactured by Eli Lilly and
Company.
• Subsequently other SSRIs were introduced.

Zhong et al., 2011

 Drug Profile
Name Escitalopram

Drug Class Selective Serotonin Reuptake

Inhibitors
Chemical Formula C20H21FN2O

Weight Average: 324.3919

Half-life 27-32 hours

Bioavailability 80%

Route of Administration By mouth

Log P value 2.63

Escitalopram: Uses, Interactions, Mechanism of Action | Drug Bank Online, n.d.​

 HOW DO ANTIDEPRESSANTS WORK?

Primary molecular
target for
Escitalopram is
serotonin transporter
[SERT] .

Escitalopram is responsible
for serotonin or 5-
hydroxytryptamine [5-HT ]
reuptake at the terminals
and cell bodies of
serotonergic neurons.

Zhong et al., 2011c

 MECHANISM OF ACTION
• Escitalopram and SSRIs inhibit the
function of serotonin
transporter[SERT] by binding to its
1. primary binding site where 5-HT (5-
hydroxy tryptamine) binds.

• Inhibition of SERT results in

increase 5-HT levels in the
2. synapses of brain.

• Enhanced serotonergic
neurotransmission are the basis
for the antidepressant effect of
3. drugs.

Zhong et al., 2011b

 • Addition , to primary binding site allosteric sites
4 may exist on serotonin transporter[SERT]

• Escitalopram binds to the allosteric site on

serotonin receptor.[SERT]
5

• Modulate properties of primary binding site ,

without directly affecting 5-HT uptake.
6

Zhong et al., 2011b

ESCITALOPRAM

Better Significant
Low
efficacy and dose-
duration of
tolerability response
sick leave .
profile relationship

Zhong et al., 2011

 Screening methods to find a lead compound

1. 2D Fingerprint-Based Screening:
- The authors used 2D pharmacophore-based and structural fingerprints
generated from reference ligands to screen drug-like compounds.
- Lipinski's "rule of 5" and Veber filters were applied
- The compounds were filtered based on basic properties and ADMET

2. 3D Pharmacophore-Based Screening:
- Ten 3D pharmacophore models were constructed based on reference ligands.
- Compounds passing the 2D fingerprint-based screening
- Approximately 2300 unique compounds passed this screening step.

3. Flexible Docking:
- A homology model of SERT in an outward-open conformation was used for docking.
- Compounds passing the pharmacophore-based screening were docked
into multiple conformations of the ligand binding pocket.
- Around 564 unique compounds passed.
(Gabrielsen M et.al, 2014)
4. In Vitro Evaluation of Virtual Hits:​
- A total of 202 compounds from 37 chemotypes were selected for in vitro screening using a radioligand
competition binding assay.​
​
5. Hit-to-Lead (H2L) Screening:​
- An in silico H2L screening was performed using core structures of the identified compounds.​
- The druglike subsets of the databases were screened, and compounds passing basic property and
ADMET filters were subjected to 3D pharmacophore-based screening and flexible docking.​
- Active analogues were identified, and compounds with higher affinity than their "parent" compounds
were identified in some chemotypes.​

(Gabrielsen M et.al, 2014)​

 In Vitro Radioligand Competition Binding Assays

202 compounds from 37 chemotypes were screened in vitro using a [3H]-

citalopram competition binding assay.

- 23 compounds showed at least 30% inhibition of [3H]-citalopram

binding at a specific concentration and were further evaluated.

Additionally, less-potent compounds were selected to gather structure-

activity relationship (SAR) data and increase structural diversity.

46 compounds from 22 chemotypes were evaluated using full binding

assays.

24 compounds exhibited strong affinity (Ki ≤ 1000 nM), 13 compounds

had moderate affinity (Ki between 1000 and 3100 nM), and 9
compounds were nonbinders (Ki > 10,000 nM).
(Gabrielsen M et.al, 2014)​
 Hit-to-Lead (H2L) Screening

- In silico H2L screening was conducted to find analogues of the compounds

identified through virtual screening (VS).

- Using core structures of compounds from certain chemotypes as queries, around

8700 analogues were detected.

- After applying basic property and ADMET filters, 5000 compounds remained,
which further reduced to 3855 unique compounds through 3D pharmacophore-
based screening.

- Finally, 504 unique compounds passed through flexible docking.

198 compounds were selected for in vitro [3H]-citalopram screening during H2L.

33 compounds exhibited ≥30% inhibition of [3H]-citalopram binding and were

further evaluated.

(Gabrielsen M et.al, 2014)​

 Result
 Active analogues were found in 11 out of 13 chemotypes using the H2L approach.​

 22 of the H2L compounds had Ki values ≤1000 nM, indicating strong affinity.​

 Compounds with higher affinity than their parent compounds were identified in five chemotypes.​

In essence, this process involved identifying promising compounds through both

experimental and computational methods, narrowing down to those with strong
binding affinity for further evaluation and potential development as leads for drug
discovery.

(Gabrielsen M et.al, 2014)​

 INTERMOLECULAR FORCES

2-Dimensional 3-dimensional
structure structure
PubChem, n.d.
 Key points regarding ​ the SAR of escitalopram
• ​
Stereochemistry: The S-enantiomer of citalopram, escitalopram, exhibits significantly higher potency and selectivity for the serotonin
transporter (SERT) compared to the R-enantiomer.​
• ​
Chirality: The specific stereochemistry of escitalopram's chemical structure is essential for its pharmacological activity. Changes in
stereochemistry can alter potency and selectivity. ​
​ The presence of the amine group is crucial for
The aromatic rings in escitalopram contribute to serotonin reuptake inhibition activity.
its hydrophobic interactions with the Modifications or substitutions in this group
serotonin transporter. can affect activity.​​

Fluorophenyl ring: The fluorine atom on the

phenyl ring enhances potency and selectivity for
SERT.

Carbonitrile group: Plays a role in maintaining the Dihydroisobenzofuran ring: Provides structural
pharmacological activity of the compound. stability and may contribute to binding interactions
Modifications to this group may impact potency with the serotonin transporter.
and selectivity.​

(Bogeso et al, 2012)

 03
Pharmacokinetic
 Absorption
 For oral administration, escitalopram is rapidly and nearly completely absorbed.

 Escitalopram undergoes passive diffusion across the intestinal mucosa in the

jejunum and ileum, driven by concentration gradients, without requiring energy
input or carrier molecules.

 Estimated bioavailability: 80% with a low first-pass effect.

 Steady-state concentrations: after approximately 7-10 days of administration.

 Co-administration of escitalopram with food: No significant effect.

 Cmax: within 3.0 ± 1.5 hours.

(Rao et al, 2007)

 Distribution
 Escitalopram is widely distributed throughout tissues, with an apparent
Vz/F after oral administration of 1100L.

 Escitalopram exhibits low protein binding (average 56%) over a wide

range of concentrations, indicating a low potential for drug displacement
interactions.

 P-glycoprotein acts as an efflux transporter at the blood-brain barrier,

limiting the entry of its substrates into the brain; knockout mouse studies
suggest it transports antidepressants, like escitalopram, out of the brain
into the bloodstream, reducing their brain accumulation.

(Rao et al, 2007)

 Metabolism
Escitalopram

Main
In Brain
hepatic

Escitalopram propionaldehyde MAO-A

Oxidative N-demethylation MAO-B
CYP3A4
CYP2C19
CYP2D6
S-DCT Oxidation

By- AO

Demethylation
By- Escitalopram Propionic acid
CYP2D6

S-DDCT (Rao et al, 2007)

 Excretion
 The disposition of escitalopram is biphasic with a t 1/2 of about 27–33
hours in young healthy volunteers, allowing for once-daily administration.

 the principal routes of elimination of escitalopram and its metabolites are

hepatic and renal.

 Renal excretion of metabolites represents the major route of elimination,

with only a small fraction voided with faeces. Only 8–10% of the dose is
excreted unchanged.

 No pharmacokinetic studies of escitalopram have demonstrated

interconversion of the S- and R-enantiomers of escitalopram in plasma or
urine.

(Rao et al, 2007)

 TOXICITY
AND
SAFETY STUDY
​
 MICRONUCLEUS ASSAY

Study Control group of pregnant female mice

0.06 mg/kg/day, 0.12 mg/kg/day and 0.24 mg/kg/day of dose concentration

Extraction of bone marrow cells on 19th day of gestation

In mothers In embryos
Bone marrow smears treated with 1% Extraction of blood from tail of
sodium citrate solution embryos
Resuspension of cell pellet in 5% Treatment with 1% sodium citrate
fetal calf serum in PBS solution
Preparation of smear + addition of Resuspension of cell pellet in 5%
methanol for 15 min fetal calf serum in PBS

Preparation of smear + addition of

Staining with Giemsa stain
methanol for 15 min

500 cells per each female and embryo were scored Roshdy et al.,2004
Cobanoglu et al.,2018
 RESULTS

Effect of Escitalopram on days 1 to 18 of gestation

Roshdy et al.,2004 Skeletal observations of fetuses from female mice Receiving (Escitalopram) on days 1-18 of gestation
 Results of micronucleus tests in mothers and embryos after maternal oral administration with (Escitalopram)

Escitalopram

Escitalopram

Escitalopram

Roshdy et al.,2004
Effect of (Escitalopram) maternal treatment on embryos at 19 days of gestations
 REPEAT DOSE TOXICITY

STUDY RESULT
Body weight and relative organ weight of treated mice
●Group I (control): Animals were orally
administered water through an intubation
tube once a day for a continuous period of
30 days and 60 days.
●Group II: Animals were orally
administered escitalopram oxalate at a
dose of 10 mg/kg body weight per day,
dissolved in water through an intubation
tube once a day for a continuous period of
30 days and 60 days.
●Group III: Animals were orally • Repeated administration of Escitalopram led to significant
decreases in body weight and organs weight.
administered escitalopram oxalate at a
• Escitalopram oxalate at dose of 20mg/kg b.w. per day for 60
dose of 20 mg/kg body weight per day, days exposure induces male reproductive toxicity and may
dissolved in water through an intubation consequently contribute to male infertility
tube once a day for a continuous period of
30 days and 60 days. Agrawal et al., 2022
Clinical
Trials
 Phase- I

Study design & goal: To compare the bioequivalence of two

formulations of escitalopram oxalate 20 mg tablets in terms of
bioavailability and tolerability in healthy Chinese male and female
subjects.

Inclusion: Healthy male or female subjects aged 18 to 65 years who

provided informed consent, Males must weigh at least 50 kg, females
at least 45 kg, with a BMI between 19 and 26 kg/m².

Exclusion: Presence of liver dysfunction, renal insufficiency, or

abnormal hematology
• History of epilepsy, drug or alcohol abuse.
• Smoking more than 5 cigarettes per day.
• Consumption of chocolate, caffeine, or xanthine-containing foods
within 48 hours of the first dosing day.

Li et al.,2020
Methods:
 Randomized, single-blind study under fasting and fed
conditions, with a 21-day washout period, 24 healthy
subjects.
 Blood samples collected over 2, 4, 6, 8 hours after dosing.
 Escitalopram levels in plasma measured using high-
performance liquid chromatography with tandem mass
spectrometry.

 Safety evaluation parameters included adverse events

(AEs), severe adverse events (SAEs), concomitant
medication, changes in clinical laboratory results
(hematology, blood chemistry, and urinalysis), clinical
symptoms, vital signs, electrocardiograms (ECGs), and
physical examination.

Li et al.,2020
Results:
 No significant changes in laboratory tests, results of physical
examinations, or vital signs of enrolled subjects before and after
oral administration of escitalopram oxalate 20 mg tablets of the
test or reference formulation under fasting and fed conditions.
 Fasting test: 9 people had 26 side effects, with 15 of these possibly
linked to the medication. One person left the study due to
vomiting.
 Fed Test: 10 people experienced 12 side effects, and 11 of these
were possibly due to the medication. Two people dropped out
because of vomiting.

Conclusion:
Escitalopram oxalate 20 mg tablets produced in China were safe to
the reference formulation (Lexapro®) in healthy Chinese male and
female subjects under fasting and fed conditions.

Li et al.,2020
 Fasting Fed
Test (n=23) Reference Test (n=24) Reference
(n=22) (n=22)
Case Subject Case Subject Case Subject Case Subject
No. (%) No. (%) No. (%) No. (%)
AEs 14 6 (26.09) 12 6 (27.27) 7 7 5 4 (18.18)
(29.17)
ADR 9 4 (17.39) 6 5 (22.73) 6 6 5 4 (18.18)
(25.00)
SAEs 0 0 (0.00) 0 0 (0.00) 0 0 (0.00) 0 0 (0.00)
SADR 0 0 (0.00) 0 0 (0.00) 0 0 (0.00) 0 0 (0.00)
AEs leading 1 1 (4.35) 0 0 (0.00) 2 2 (8.33) 0 0 (0.00)
to dropout
ADR leading 1 1 (4.35) 0 0 (0.00) 2 2 (8.33) 0 0 (0.00)
to dropout
Li et al.,2020
 Phase- II
Study design & goal: To determine whether the use of an
antidepressant (escitalopram) can prevent depressive episodes that
appear during the treatment with peg-interferon and ribavirin in
patients with chronic hepatitis C.
Inclusion: Patients with chronic hepatitis C who are going to initiate
treatment with peginterferon alfa2a + ribavirin, Age 18-65 years. If
female, they are not in fertile period or they use barrier
contraceptives.
Exclusion: Liver issues, low blood count, anemia, serious comorbid
conditions, pre-existing mental disorders
Methods:
• Multicenter, randomized, double-blind, placebo-controlled trial in
133 chronic hepatitis C patients assigned to receive escitalopram
or placebo during the first 12 weeks of treatment.
• Patients diagnosed with chronic hepatitis C, scheduled for
treatment with peginterferon-alfa2a + ribavirin without mental
disorders requiring active psychotropic treatments.
• Appearance of major depressive episodes according to DSM-IV
criteria.
Quevedo et al., 2010
• Scores on the Montgomery-Asberg Depression Rating Scale.
• Evaluations at 4, 8, and 12 weeks of interferon treatment.
• Up to 6 months of follow-up after interferon treatment ends.

RESULTS:
Major depression incidence was low at 5.4%, with no significant
difference between the escitalopram (7.6%) and placebo (3.2%)
groups.
• Both MADRS and HAMDS scores significantly increased during
treatment, indicating worsening depression and anxiety, but no
differences were found between treatment groups.
• A sustained virological response, indicating effective treatment of
hepatitis C, was achieved by 69.2% of patients, with similar rates
in both placebo (70.4%) and escitalopram (67.9%) groups.

CONCLUSION:
An antidepressant like escitalopram doesn't prevent interferon-
induced depression in the first 12 weeks of treatment for chronic
hepatitis C patients with low psychiatric risk.

Quevedo et al., 2010

 Phase- III

Study design & goal

•a) Double-blind, parallel assignment, randomized and innovator-controlled study.
•b) 260 subjects were investigated from 6 centers in China.
•c) To compare the efficacy and safety of generic escitalopram (study group) & Lexapro (control group)

Inclusion
•a)patients diagnosed with major depressive disorder
•b) between 18 & 65 years
•c) not under psychoactive medications
•d) HAMD -17 score ≥ 20

Exclusion
•a) suicidal tendency b) serious physical illness c) history of epilepsy d) closed- angle glaucoma e)
dependence on alcohol f) pregnant - lactating g) drug allergy h) poor response to escitalopram

Method
•Escitalopram and Lexapro (10 mg/Tablet) given orally once.
•Initial dose: 10 mg/d, At the end of second week: 20 mg/d
•Efficacy assessed by HAMD-17
•Safety assessed by Adverse events reported
Quevedo et al., 2010
Results:
• 27% dropped out from the generic group, 25% from Lexapro
group over 8 weeks.
• Average score improvement was similar: 13.9 in generic, 14.3 in
Lexapro.
• About 69% in generic and 67% in Lexapro showed significant
improvement.
• 51% in generic and 49% in Lexapro fully recovered.
• Main side effects were dry mouth, nausea, and dizziness for
generic; nausea, fainting, and drowsiness for Lexapro.

Conclusion: Generic escitalopram is as effective and safe as Lexapro

for treating major depression.
Regulatory
Affairs
Escitalopram Regulatory Timeline Friesen et al.,2015

March 2002: January 2012:

Escitalopram Canada warning &
Launched label changes
in market
August 2011: FDA March 2012: FDA
January 2004: warning adds additional
Generic Escitalopram labeling changes
1998 Citalopram Launched in Canada
developed by
Lundbeck
98

02

08

14
89

00

04

06

10

12
19

20

20

20
19

20

20

20

20

20
Study Period:1999-2014

Prewarning era
 FDA Pharmaceutical Development and Approval process

IND submitted NDA submitted FDA Approval

Drug Pre-Clinical research Clinical Trial FDA reviews NDA Manufacturing

Discovery and development
and Drug appears on
Development Initial synthesis of Research and development FDA expects review data the market
substance (All Trials approved by
2-10 Years IRB) Company address FDA Post market
Laboratory studies and concerns surveillance
animal testing Phase I-Testing in healthy
subjects Advisory hearing maybe Follow up studies
Institutional review called and inspection
boards Phase II- Testing in
individuals with the
disease. 1-2 Years

3-6 Years Phase III- Larger scale

testing in individuals with
IND: Investigation New Drug the disease.
NDA: New Drug Application
FDA: US Food & Drug Administration 6-7 Years https://www.allfordrugs.com/fdas-drug-review-process/
 What is IND….?
Sponsor-investigator
initiate IND to FDA

 The IND application must contain 30-day multidisciplinary review by clinical,

information in three broad areas: chemistry, pharmacology/toxicology, and
statistical reviewers, and other consultants

 Animal Pharmacology and

Sponsor-
Toxicology Studies
investigator
 Manufacturing Information submits response to Safe to
 Clinical Protocols and Investigator address the FDA’s
No
proceed?
concerns Yes
Information.

 This application includes Sponsor-

investigator may Drug may be
comprehensive data from not initial trial shipped
preclinical studies, as well as Clinical hold letter
sent to sponsor-
details of proposed clinical trials, investigator
including protocols, dosing including the basis The FDA notifies
regimens, and safety monitoring for the hold sponsor- Sponsor-
investigator of investigator may
plans. concerns (usually initiate trial
by telephone)
(Research, 2018)
What is NDA…?
NDA Submission:
Researchers compile data from preclinical and clinical studies

Regulatory Review:
Agencies thoroughly assess the NDA, evaluating safety,
efficacy, quality, clinical trial data, manufacturing, labeling,
and risk management plans.

Advisory Committee Review:

Regulatory agencies may convene independent expert
committees to review the NDA and offer recommendations.

Approval Decision:
Regulatory agencies decide whether to approve the new drug
based on NDA review and advisory committee input, possibly
with conditions for continued safety and efficacy monitoring.
(Research, 2018)
 Post-
Market
Surveillance​
 Increased Risk of Bleeding
Sexual Dysfunction
Adverse  Pregnancy Complication
Serotonin syndrome
Indigestion

Effect Suicidal thoughts and behaviors in

adolescents and young adults
Psychiatric Disorder

Yawning

Concomitant use with SSRIs, SNRIs,

Drug or Tryptophan is not recommended.
Headache
Interaction Use caution when concomitant use
with drugs that affect Hemostasis
(Aspirin, Warfarin).

Fatigue
https://www.fda.gov/media/135185/download
https://www.fda.gov/media/135185/download
 FDA Adverse Event Reporting System

 The FDA Adverse Event Reporting System (FAERS) is a database that contains
information on adverse events and medication error reports submitted to the FDA.
 The database is designed to support the FDA's post-marketing safety surveillance
program for drug and therapeutic biologic products.
 The informatic structure of the FAERS database adheres to the international safety
reporting guidance issued by the International Conference on Harmonization (ICH
E2B).
 Adverse events and medication errors are coded to terms in the Medical Dictionary for
Regulatory Activities (MedDRA) terminology.

https://fis.fda.gov/sense/app/95239e26-e0be-42d9-a960-9a5f7f1c25ee/sheet/45beeb74-30ab-46be-8267-5756582633b4/state/analysis
 Summary
Escitalopram, a first-line treatment for major anxiety disorder, targets the serotonin
transporter with its efficacy underscored by structural features like chirality.

Through extensive virtual screening, pharmacophore analysis, and clinical trials, its
safety and effectiveness were established, despite potential pregnancy risks such as
mutagenicity and fetal malformations.

Metabolism occurs primarily in the liver, with a half-life of 27-33 hours, leading to
renal excretion of its metabolites.

While escitalopram has been proven not to prevent interferon-induced depression,

its market surveillance ensures continuous assessment of its safety profile, guided by
regulatory frameworks to manage its clinical use responsibly.
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 References
 Research, C. F. D. E. A. (2018, August 24). Investigational New Drug Applications Prepared and Submitted by Sponsor-
Investigators. U.S. Food And Drug Administration.
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/investigational-new-drug-applications-prepared-and-sub
mitted-sponsor-investigators
 Research, C. F. D. E. A. (2022, July 20). Investigational New Drug (IND) Application. U.S. Food And Drug Administration.
https://www.fda.gov/drugs/types-applications/investigational-new-drug-ind-application#FDA%20Guidances%20for%20Investigation
al%20New%20Drugs
 Research, C. F. D. E. A. (2022, January 21). New Drug Application (NDA). U.S. Food And Drug Administration.
https://www.fda.gov/drugs/types-applications/new-drug-application-nda
 Research, C. F. D. E. A. (2015, August 24). FDA’s Drug Review Process: Continued. U.S. Food And Drug Administration.
https://www.fda.gov/drugs/information-consumers-and-patients-drugs/fdas-drug-review-process-continued
 https://www.allfordrugs.com/fdas-drug-review-process/
 Friesen, K. J., & Bugden, S. C. (2015). The effectiveness and limitations of regulatory warnings for the safe prescribing of
citalopram. Drug, healthcare and patient safety, 7, 139–145. https://doi.org/10.2147/DHPS.S91046
 https://www.fda.gov/media/135185/download
 Rao, N. (2007, January 1). The Clinical Pharmacokinetics of Escitalopram. Clinical Pharmacokinectics.
https://doi.org/10.2165/00003088-200746040-00002
 References

Ø Gabrielsen M, Kurczab R, Siwek A, Wolak M, Ravna AW, Kristiansen K, Kufareva I, Abagyan R,

Nowak G, Chilmonczyk Z, Sylte I, Bojarski AJ. Identification of novel serotonin transporter compounds by virtual
screening. J Chem Inf Model. 2014 Mar 24;54(3):933-43. doi: 10.1021/ci400742s. Epub 2014 Feb 26. PMID:
24521202; PMCID: PMC3982395.
Ø Diez-Quevedo C, Masnou H, Planas R, Castellví P, Giménez D, Morillas RM, Martín-Santos R, Navinés R, Solà R,
Giner P, Ardèvol M, Costa J, Diago M, Pretel J. Prophylactic treatment with escitalopram of pegylated interferon
alfa-2a-induced depression in hepatitis C: a 12-week, randomized, double-blind, placebo-controlled trial. J Clin
Psychiatry. 2011 Apr;72(4):522-8. doi: 10.4088/JCP.09m05282blu. Epub 2010 Oct 5. PMID: 21034680.
Ø Yimin YU, Huafang LI, Biao WANG, Keqing LI, Xiufeng XU, Jianguo SHI, Chengge GAO, Qingrong TAN, 2013,
efficacy and safety of generic escitalopram versus Lexapro in the treatment of major depression: multicenter
double-blinded randomized controlled trial.
Ø Li Q, Huo H, Hu W, Sui Y, Tang Y. Comparison of Bioavailability and Bioequivalence of Generic and Brand Name
Formulations of Escitalopram Oxalate Tablets in Healthy Chinese Population Under Fasting and Fed Conditions.
Drug Des Devel Ther. 2020 Nov 24;14:5167-5177. doi: 10.2147/DDDT.S271970. PMID: 33262577; PMCID:
PMC7699441.
Ø Roshdy, H. M., & Shoman, T. M. (2004). Cytogenetic and developmental effects of antidepression drug (Cipralex)
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 References
 Cobanoglu, H., Coskun, M., Çayir, A., & Coskun, M. (2018). In vitro genotoxic and cytotoxic effects of doxepin
and escitalopram on human peripheral lymphocytes. Drug and Chemical Toxicology, 41(2), 238-244.
 AGRAWAL, K., SHAHANI, L., & BHATNAGAR, P. (2023). Evaluation of escitalopram induced reproductive
toxicity in male Swiss albino mice. Journal of Research in Pharmacy, 27(1).
 Zhong, H., Haddjeri, N., & Sánchez, C. (2011). Escitalopram, an antidepressant with an allosteric effect at the
serotonin transporter—a review of current understanding of its mechanism of action. Psychopharmacology, 219(1),
1–13. https://doi.org/10.1007/s00213-011-2463-5
 Chu, A., & Wadhwa, R. (2023, May 1). Selective serotonin reuptake inhibitors. StatPearls - NCBI Bookshelf.
https://www.ncbi.nlm.nih.gov/books/NBK554406/
Thank You.!

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