Case report: Escitalopram-associated lower limb edema

Case report: Escitalopram-

associated lower limb edema

Mohamed Hassan Ahmed

, Mena Al-Kubaisi

Safa Abdulmajeed

Al-Rawi

, Omar Hosam Salama

and Hebah Mahmoud Abutayyem

Consultant Psychiatrist, Sheikh Khalifa Medical City, Ajman, United Arab Emirates,

Bachelor of

Medicine and Bachelor of Surgery (MBBS), Ajman University, Ajman, United Arab Emirates,

Pharmacy

Department, Sheikh Khalifa Medical City, Ajman, United Arab Emirates

Escitalopram is widely prescribed for the treatment of major depressive disorder

and generalized anxiety disorder with a well-documented side effects proﬁle.

Peripheral edema, however, is a rarely reported adverse reaction that warrants

further work up. This paper summarizes the case of a 58-year female patient who

developed transient bilateral peripheral edema following the administration of

low dose escitalopram. This case underscores the necessity for clinicians to be

familiar with even rare potential side effects of commonly prescribed

medications. It also suggests a need for patient education regarding the

importance of reporting new symptoms promptly.

KEYWORDS

edema, drug-associated, side effects, SSRIs, escitalopram

1 Introduction

Escitalopram, a selective serotonin reuptake inhibitor (SSRI), is commonly utilized in the

treatment of major depressive disorder and generalized anxiety disorder due to its efﬁcacy and

relatively favorable side effect proﬁle (1). Despite its widespread use, certain adverse drug

reactions (ADRs) remain less characterized in the medical literature. Peripheral edema is

infrequently associated with SSRI (1). Peripheral edema typically presents as a swelling in the

lower extremities. It has been associated with a myriad of etiologies, including cardiac, renal,

hepatic, or venous insufﬁciency, as well as several pharmacological agents (2). The incidence

of drug-associated peripheral edema is often underreported and may lead to non-compliance

or unnecessary medical investigations if not promptly recognized (2). We report a case of a

58-year-old-year-old female patient who developed transient bilateral peripheral edema

following the administration of escitalopram. The case presents a unique instance of an

adverse drug reaction (ADR) to a widely used medication, distinguished by the absence of

other typical causes of edema. This is conﬁrmed through extensive diagnostic tests.

Importantly, the connection between the medication and edema is underscored by the

precise timing of the reaction and the swift resolution after stopping the medication, which

Frontiers in Psychiatry frontiersin.org01

OPEN ACCESS

EDITED BY

Mirko Manchia,

University of Cagliari, Italy

REVIEWED BY

Yassir Mahgoub,

The Pennsylvania State University,

United States

Takahiko Nagamine,

Sunlight Brain Research Center, Japan

*CORRESPONDENCE

Mohamed Hassan Ahmed

[email protected]

RECEIVED 02 March 2024

ACCEPTED 15 April 2024

PUBLISHED 26 April 2024

CITATION

Ahmed MH, Al-Kubaisi M, Al-Rawi SA,

Salama OH and Abutayyem HM (2024)

Case report: Escitalopram-associated

lower limb edema.

Front. Psychiatry 15:1394813.

doi: 10.3389/fpsyt.2024.1394813

and Abutayyem. This is an open-access article

distributed under the terms of the Creative

Commons Attribution License (CC BY). The

use, distribution or reproduction in other

forums is permitted, provided the original

author(s) and the copyright owner(s) are

credited and that the original publication in

this journal is cited, in accordance with

accepted academic practice. No use,

distribution or reproduction is permitted

which does not comply with these terms.

TYPE Case Report

PUBLISHED 26 April 2024

DOI 10.3389/fpsyt.2024.1394813

substantiates a direct relationship between the two. Through this

report, we aim to highlight the clinical approach to diagnosing and

managing such an atypical presentation and discussing the broader

implications on management with psychotropic medications (3).

2 Case presentation

A 58-year-old female, previously healthy with unremarkable

medical and family history, presented with disturbed sleep. She

gradually developed insomnia and appetite loss over one month,

prior to her visit, and she also suffered from low mood. A full medical

assessment was done in a private hospital which indicated no

underline medical explanation for her symptoms. A plan was

made, and she was provided with psychoeducation and a

therapeutic regimen of escitalopram, initiated at a dose of 5 mg/

day, for 30 days, to manage her depressive episode. Later, she

presented to our outpatient department for follow up with an acute

onset of bilateral lower limb swelling. This event occurred after 6 days

from the commencement of the therapeutic regimen. Notably, the

patient had not reported any recent alterations in her medication

regimen or any signiﬁcant medical history that could contribute to

the current symptomatology. Upon examination, the patient

exhibited bilateral peripheral edema, characterized by swelling

extending from the dorsum of the feet to the mid-calves. The

edema was pitting, without accompanying erythema, ulceration, or

discoloration of the overlying skin, which may have suggested an

inﬂammatory or infectious etiology. Her cardiovascular assessment

did not reveal any signs suggestive of congestive heart failure, and her

abdominal examination was unremarkable, discounting hepatic or

renal pathology as a primary cause.

3 Diagnostic assessment

Laboratory investigations were promptly conducted, which

inclu ded a complete blood count, renal function panel, which

included electrolytes such as calcium, sodium, potassium and

chloride, liver function panel, thyroid function tests, and a

comprehensive urinalysis. The results of these tests were largely

within normal parameters, excluding the common systemic causes

of edema. However, the urinalysis yielded atypical ﬁnding s

including pyuria, hematuria, ketonuria, and hemoglobinuria,

indicating a possible acute urinary pathology. Additionally, the

patient’s glycemic control was brought into question by an elevated

HbA1c level, and liver enzyme disturbances were evidenced by

increased total and indirect bilirubin, AST, and GGT levels. Serum

lipid proﬁle, C-reactive protein (CRP), B-type natriuretic peptide

(BNP), and troponin T results were within normal ranges, ruling

out cardiovascular causes. With the exclusion of more common

etiologies and the temporal association between the initiation of

escitalopram and the development of edema, a provisional

diagnosis of drug-associated periphe ral edema was considered.

Escitalopram was subsequently discontinued and resulted in a

rapid and complete resolution of edema within three days, further

substantiating the causative relationship.

Patient perspective

Initially, the patient was concerned about the leg edema she

started to develop, not sure the reason behind it. Following the

identiﬁcation and ce ssation of the causative medicine and the

initiation of an alternate medication, the patient was happy that

her leg edema was resolved quickly and still willing to adhere to her

new medication. She was aware of the signiﬁcance of reporting any

worries and not ignoring any signs.

4 Discussion

Drug-associated edema refers to the abnormal accumulation of

ﬂuid in the interstitial spaces of the body as a result of medication.

Although the edema can be frequent with some drugs, it remains

inadequately understood and underdiagnosed. This poor

characterization concerns both their mechanism and action. And

the reporting system for peripheral edema varies from study to

study. Medications from different classes have been implicated in

causing edema, commonly with anticancer, antihypertensives,

corticosteroids, psychotropics, and many more (4). In psychiatry,

considering psychotropic drugs and their association with

peripheral edema, antipsychotics and antidepressants are mostly

reported. The medications with the highest rate of association were

mirtazapine, olanzapine, quetiapine, risperidone and pregabalin (5).

Four main mechanisms account for the etiology of drug-associated

edema: sodium and water retention (re nal edema) , increa sed

capillary permeability (permeability edema), lymphatic

insufﬁ ciency (lymphedema), and precapillary arteriolar

vasodilation (vasodilatory edema) (4).

The estimated incidence of peripheral edema can vary widely

depending on the population studied and the medications involved.

For example, peripheral edema is a common side effect of calcium

channel blockers (CCBs), with an incidence ranging from 2% to

25% depending on the type of CCB, dosage, and durati on of

therapy. Amlodipine, in particular, is more likely to lead to

peripheral edema compared to n ondihydropyridine CCBs and

newer lipophilic DHP CCBs (6). Gabapentin is another

medication that can cause peripheral edema, reported at an

incidence rate of 2% to 8%. The occurrence of edema seems to be

dose-related and more common in the elderly population. In a

pooled analysis from clinical trials, the incidence increased from

1.4% to 7.5% with doses of 1800 mg/day and up to 12.3% at 3600

mg/day. However, there are cases of edema developing at doses

lower than 1800 mg/day, indicating that it might not always be

dose-related (7 ). It’s also important to note that while CCB-

associated edema is a frequent issue leading to the use of

diuretics, this type of edema is not caused by ﬂuid overload, and

using diuretics can pose risks, especially in older adults (6). As for

the general prevalence of peripheral edema, one source suggested

that approximately 20% of adults older than 50 years may

experience edema (8).

In antidepressants, nearly all major classes were found to be

associated with edema in a systematic review comparing them. Of

these medications, trazodone is the most implicated, followed by

Ahmed et al. 10.3389/fpsyt.2024.1394813

Frontiers in Psychiatry frontiersin.org02

mirtazapine in second place and escitalopram in third. Particularly,

SSRIs contributed 24.4% compared to the other classes (9). No clear

conclusion is made regarding the possible etilology of anti-

depressant associated edema, as most studies are case reports, but

the proposed etiology involves the antagonism of a1 adrenergic

receptors and 5HT2A receptors, leading to vascular smooth muscle

relaxation, increased capillary vasodilatation, hydrostatic pressure,

and subsequent edema (5)(9). Another possible mechanism

suggests that 5-HT1B receptors are in endothelial cells, and

stimulation of this receptor by increased serotonin induces

vasodilation through the production of nitric oxide (NO) (10).

Bilateral leg edema was reported in some cases with the use of

escitalopram. Most of the patients were diagnosed with major

depressive disorder and started on escitalopram in different doses,

with a minimum dose ranging from 10 mg to 30 mg/day as the

highest dose reported (11). In our case, the patient was started on 5

mg/day of escitalopram. The duration of the time from starting the

medication to reporting the edema ranged between one week to

three weeks (12). In our case, similarly, edema was reported 6

days later.

Reviewing the medication history is crucial when the cause of

bilateral lower limb edema is unknown. If any medications are

suspected to be associated with the edema, they must be stopped,

or their dosage reduced. In addition, the basic laboratory work up

should focus initially on excluding major systemic diseases, which

include heart failure, renal disease, liver disease and DVT. Other

possible differential diagnosis include hypothyroidism, lymphedema

due to lymphatic obstruction after trauma or surgery, angioedema

and urticaria secondary to allergic reaction. Systemic evaluation

includes complete blood count, urinalysis, electrolytes, creatinine,

blood sugar, thyroid stimulation hormone, albumin, and other tests

for speciﬁc indication. Table 1 shows the suggested additional

workup for the common differential diagnosis (13).

In our case, blood tests that include kidn ey function, live r

function, urine analysis, complete blood count, thyroid function

test, cardiac tests, and electrolytes showed no signiﬁcant results or

indication of underlying disease. Risk assessment for thrombosis

was done which resulted in a very low risk for thrombotic disease.

However, thrombotic assessment such duplex ultrasound and D-

dimer to rule out deep vein thrombosis (DVT) were not done.

Drugs interaction or adverse drug reaction are ruled out because the

patient only takes lorazepam before bed (14). Medication associated

edem a was s uspected, and escitalopram was discontinued, the

edema resolved after 3 days. Despite escitalopram being a

commonly prescribed medication for mood disorders, this case

report highlights a rare side effect of the drug, edema. Whic h

emphasizes the need for additional research on the side effects of

SSRIs and draws attention to the signiﬁcance of attentive patient

monitoring, educating patients about the potential for edema

development even at low therapeutic d oses, and promptly

reporting any such occurrences.

5 Conclusion

Escitalopram associated bilateral leg edema is a side effect that

should be considered when prescribing despite its rarity. Edema can

occur at low therapeutic doses and in the absence of other possible

medical etiologies. This indicates the further need for healthcare

professionals to maintain a broad differential diagnosis when

encountering peripheral edema, considering drug associated causes in

the context of recent medication changes. This shows the importance of

close therapeutic monitoring, blood tests, and knowledge of underlying

medical issues, drug interactions, and potential adverse effects.

Data availability statement

The original contributions presented in the study are included

in the article/supplementary material. Further inquiries can be

directed to the corresponding author.

Ethics statement

Written informed consent was obtained from the individual(s)

for the publication of any potentially identiﬁable images or data

included in this article.

Author contributions

MHA: Writing – review & editing, Supervision. MA: Writing –

review & editing, Writing – original draft, Project administration.

SA: Writing – original draft, Writing – review & editing. OS:

Writing – original draft, Writing – review & editing. HM:

Writing – review & editing.

Funding

The author(s) declare that no ﬁnancial support was received for

the research, authorship, and/or publication of this article.

Conﬂict of interest

The authors declare that the research was conducted in the

absence of any commercial or ﬁnancial relationships that could be

construed as a potential conﬂict of interest.

TABLE 1 Differential diagnosis and suggested work-up for medication-

associated lower limb edema.

Differential

Diagnosis

Diagnostic studies

Heart failure ECG, Echocardiogram, chest radiograph, brain

natriuretic peptide

Liver disease ALT, AST, total bilirubin, alkaline phosphatase,

prothrombin time, serum albumin

Kidney disease Urinalysis with exam of sediment, serum lipids

DVT D-dimer, doppler exam

Lymphedema Abdominal/pelvic CT scan

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Publisher’s note

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authors and do not necessarily represent those of their afﬁliated

organizations, or those of the publisher, the editors and the

reviewers. Any product that may be evaluated in this article, or

claim that may be made by its manufacturer, is not guaranteed or

endorsed by the publisher.

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