Content uploaded by Robert Croos
Author content
All content in this area was uploaded by Robert Croos
Content may be subject to copyright.
Available via license: CC BY 4.0
Content may be subject to copyright.
BioMed Central
Page 1 of 4
(page number not for citation purposes)
BMC Ophthalmology
Open Access
Case report
Citalopram associated with acute angle-closure glaucoma: case
report
Robert Croos
1
, Srinivasa Thirumalai*
3
, Sabit Hassan
2
and Jane Da
Roza Davis
1
Address:
1
Department of Psychiatry, Prospect Park Hospital, Reading, RG30 4EJ, UK,
2
Department of Ophthalmology, Royal Berkshire Hospital,
Reading, RG1 5AN, UK and
3
Department of Psychiatry, Marlborough House Regional Secure Unit, Milton Keynes Hospital Site, Eaglestone,
Standing Way, Milton Keynes, MK6 5NG, UK
Email: Robert Croos - Robert.Croos@berkshire.nhs.uk; Srinivasa Thirumalai* - Srinivasa.Thirumalai@btinternet.com;
Sabit Hassan - Sibit.Hasan@aol.com; Jane Da Roza Davis - Jane.DaRozaDavis@berkshire.nhs.uk
* Corresponding author
Abstract
Background: Acute angle-closure glaucoma is a rare complication in patients receiving anti-
depressant treatment. In the following case, we report the development of acute angle closure
glaucoma in a patient who overdosed on Citalopram, an antidepressant, and discuss the possible
etiological mechanisms for the condition.
Case presentation: We report a 54 year old, Caucasian lady, with depression and alcohol
dependence syndrome, who developed acute angle-closure glaucoma after an overdose of
Citalopram, along with alcohol. She was treated with medications and had bilateral Yag laser
iridotomies to correct the glaucoma and has made complete recovery. In this case, the underlying
cause for glaucoma appears to be related to the ingestion of Citalopram.
Conclusion: The patho-physiological basis for acute angle closure glaucoma in relation to
antidepressant medications remains unclear. The authors suggest Citalopram may have a direct
action on the Iris or Ciliary body muscle through serotonergic or anti-cholinergic mechanisms or
both. This case highlights the importance of the awareness of the underlying risks, which may
predispose an individual to develop acute angle-closure glaucoma, and reminds the clinicians the
significance of history taking and examination of the eye before and after starting anti-depressants.
This area needs to be further researched.
Background
Depression is the most common psychological disorder in
the world. The prevalence of unipolar depression is esti-
mated to be between 3% and 13%, with as much as 20%
of the world adult population experiencing at least some
depressive symptoms at any given time [1]. Lifetime inci-
dence of depression is estimated to be 20% to 55%.
Approximately, 70% of moderately to severely depressed
patients respond to anti-depressant therapy [2]. SSRI are
increasingly the first line choice of anti-depressant
because of their tolerable side-effect profile and low rate
of lethality if taken in an overdose [3]. All SSRI are equally
effective in treatment for depression [4].
Citalopram is an antidepressant of the selective serotonin
reuptake inhibitor (SSRI) class. They act by producing a
Published: 04 October 2005
BMC Ophthalmology 2005, 5:23 doi:10.1186/1471-2415-5-23
Received: 03 February 2005
Accepted: 04 October 2005
This article is available from: http://www.biomedcentral.com/1471-2415/5/23
© 2005 Croos et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0
),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
BMC Ophthalmology 2005, 5:23 http://www.biomedcentral.com/1471-2415/5/23
Page 2 of 4
(page number not for citation purposes)
gradual increase in postsynaptic levels of serotonin (5-
hydroxytryptamine, 5-HT) via desensitization of the feed-
back systems that controls the rate-limiting enzyme in 5-
HT synthesis [5].
Serotonin (5-HT) receptors have been shown to be
present in human eyes [6]. Furthermore, it is reported that
Serotonin (5-HT) receptors are present at a higher concen-
tration in mammalian ciliary body and cornea than in
non-mammalian species [7]. Experimental studies have
shown that topical application of serotonin increases the
Intra-ocular pressure (IOP) in rabbit's eyes, and that 5-
caboxamidotryptamine, a 5-HT 1a receptor agonist, is
even more effective than 5-HT itself in elevating IOP [8].
Similarly, in a study of 20 consecutive depressed patients,
following of a single dose of 20 mgs Fluoxetine it was
shown to increase IOP by 4 mmHg [9]. In another study,
Ketanserin, a compound with serotonergic blocking prop-
erties, reduced IOP in both animals and humans stressing
the role of exerted by 5-HT on IOP [10].
Glaucoma is defined as a heterogeneous group of diseases
that have in common a characteristic optic neuropathy
and visual defects, for which elevated IOP is the primary
risk factor [11]. There are approximately 67 million per-
sons, worldwide, who suffer from glaucomatous disease
of the eye [12]. These figures may not include the drug-
induced glaucoma's because the precise information on
the incidence of glaucoma as a result of local or systemic
therapies is uncertain [13]. Angle-closure glaucoma is a
disease with acute onset that occurs in 1 of 1000 Cauca-
sians, about 1 in 100 Asians (especially mongoloids) and
Hispanics, and 2–4 of 100 Inuit's (Eskimos) [13].
Risk factors for angle-closure glaucoma are narrow angle
of anterior chamber, shallow anterior chamber depth,
hyperopic, small eyes, positive family history of angle clo-
sure, elderly, female sex and use of medications that cause
papillary dilatation and excitatory situations [14]. Drugs
that cause or exacerbate angle-closure glaucoma include
several classes of drugs including adrenergic agonists,
cholinergics, anti-cholinergics, sulpha-based drugs, selec-
tive serotonin reuptake inhibitors, tricyclic and tetra cyclic
antidepressants, anticoagulants and HI and H2 receptor
antagonists, especially in people predisposed with narrow
angles of anterior chamber. In some instances, bilateral
involvement and blindness have occurred [11].
The patho-physiological mechanism of SSRI induced
acute angle-closure glaucoma remains unclear, even
though anti-cholinergic adverse effects or increased levels
of serotonin, which cause partial papillary dilatation,
have been implicated [11].
Case presentation
We describe the case of a 54 year old, non-smoker, Cauca-
sian woman, a computer programmer, who was admitted
to the General Hospital in June 2003, following an epi-
sode of overdose with Citalopram and alcohol. At the
time of her admission, she gave a history of depression
and suicidal ideation for six months. She was not known
to the local psychiatric service.
The patient was discovered by her twin sister soon after
the overdose. Initially, she had disclosed to the medical
doctor admitting her that she had taken approximately 14
tablets of 20 mgs of Citalopram along with 2 bottles of red
wine. However, later on she informed us that she might
have taken up to 30 tablets of 20 mgs Citalopram. The
actual amount ingested remains unclear.
Soon after her admission, she complained of painful left
eye with blurred vision, and was seen by the Ophthalmol-
ogist, who found that our patient had an intra-ocular pres-
sure of 23 mmHg in the right eye and 60 mmHg of
mercury in the left eye (Normal IOP-10–20 mm Hg), with
left corneal edema, and fixed dilated pupils. She was not
hypermetripic and had averaged sized eyes. She was noted
to have shallow anterior chambers (central and peripheral
depth not available) in both of her eyes. A diagnosis of left
angle-closure glaucoma was made and medications were
commenced to reduce the elevated IOP. Further investiga-
tions including routine blood investigations revealed no
abnormalities. Her pulse rate and blood pressure were
normal. She had a blood alcohol level of 85 mgs/dl (Less
than 10 indicates safe levels and 50–100 indicates toxic
levels). Her blood test did not reveal any detectable levels
paracetamol or salicylates.
With regard to her background history, there was previous
episode of overdose with paracetamol tablets in 1978.
There was no history suggestive of physical illness, and
specifically, no history of previous eye problems. There
was no family history of eye related conditions. In Decem-
ber 2002, her general practitioner had diagnosed her to be
suffering from depression with harmful misuse of alco-
hol, and commenced her on Citalopram 20 mgs daily.
Later, she informed us that she had not taken any of this
prescribed medication prior to her overdose and had only
been taking Estrogens, given for hormone replacement
(Prempak-C).
Approximately 48 hours after the overdose, on examina-
tion of her eyes, she was found to have left subhyaloid and
retinal hemorrhages. After 72 hours, the visual acuity in
the right eye was 6/9 and hand movements in the left eye.
The intraocular pressures were reasonably controlled and
she had bilateral Yag laser iridotomies. Subsequently, she
was discharged to the local psychiatric unit as she contin-
BMC Ophthalmology 2005, 5:23 http://www.biomedcentral.com/1471-2415/5/23
Page 3 of 4
(page number not for citation purposes)
ued to express suicidal thoughts and was low in mood.
Apart from receiving treatment for her eye problems at the
general hospital, she was commenced on a reducing
regime of chlordiazepoxide for her alcohol dependence.
On discharge from the general hospital, she was advised
to continue on Timolol, pilocarpine and dexamethasone
eye drops for further 14 days.
She remained free of anti-depressants and her mood
improved gradually in the absence of alcohol. After 14
days, her visual acuity was noted to be 6/18 in the left eye,
which improved to 6/12 on pinhole. Her ocular condition
was noted to be stable. Her ocular pressures were 14
mmHg in the right eye and 15 mmHg in the left eye, but
still had retinal hemorrhages on the left eye, with a clear-
ing vitreous hemorrhage.
She was followed-up by the Ophthalmologists and dis-
charged from the psychiatric hospital after 4 weeks with
further community support.
In August 2004, her right eye visual acuity was noted to be
6/9, which improved to 6/6 with pinhole and her left eye
vision was 6/24, which did not improve with pinhole. She
had a
left afferent papillary deficit. The pre-retinal and ret-
inal hemorrhages had cleared, but she still had some
residual vitreous hemorrhage. Her right eye Intra-ocular
pressure was 18 mmHg and left was 19 mmHg without
any treatment. She is reviewed by the local eye clinic every
six months.
Discussion
Tricyclic antidepressants, such as, amitriptyline and imi-
pramine have been associated with acute angle closure
glaucoma [[15] &[16]]. Although there are eight reports of
glaucoma and amitriptyline, there is only one reported
case of association of amitriptyline with acute angle clo-
sure glaucoma and this had taken place following an epi-
sode of overdose [15]. In another study, four patients with
narrow angles suffered from acute angle closure glaucoma
after routinely prescribed doses of imipramine [16]. Bilat-
eral acute angle closure glaucoma has been reported in a
hypermetripic patient on venlafaxine and chlorpro-
mazine, suggesting, perhaps, this occurred by the hepatic
inhibition of chlorpromazine metabolism of venlafaxine,
increasing anticholinnergic activity, or by a direct effect of
venlafaxine on the eye, unrelated to mydriasis [17]. The
manufacturers of venlafaxine (Wyeth Laboratories) report
glaucoma as a rare adverse event. There has been one pre-
vious report of increased intraocular pressure in two
patients with known narrow angle glaucoma who began
taking venlafaxine [18].
Bilateral angle closure glaucoma and visual loss was pre-
cipitated by maprotiline and alprazolam in a 71 years old
lady with a history of depression, who had previously
complained of ocular pain and blurred vision [19]. Fluox-
etine, Paroxetine and fluoxamine have been associated
with angle closure glaucoma [[11] &[20]]. Voluntary
reporting of suspected adverse events with Fluoxetine has
identified a total of 63 cases of glaucoma in an estimated
patient population of 21 million in 1998 [21]. The man-
ufacturers of Paroxetine are aware of four cases of acute
angle closure glaucoma, and one of raised IOP in a UK
patient population of over a million in 1998 [21]. The
manufacturers of Citalopram are aware of 15 reports of
glaucoma, but causality has not been assigned in these
cases and there is no published literature concerning glau-
coma as a recognized adverse effect after overdose with
Citalopram (Lundbeck Ltd, personal communication).
To our knowledge, this is the first report of acute, unilat-
eral, angle closure glaucoma in a patient following an
overdose of Citalopram antidepressant. In our case, there
was a clear temporal link between Citalopram overdose
and the development of acute angle closure glaucoma. It
may be that the onset of glaucoma may be due to the
rapid rise in blood concentration of the drug after the
overdose (serum concentration of Citalopram was not
measured in our case). It is also possible that our patient
was predisposed to develop glaucoma due some other
unknown inherent factor. Although, it would have been
ideal to reintroduce our patient to Citalopram in order to
demonstrate causality, especially as our patient had surgi-
cal intervention in both of her eyes, we decided this was
not in the best interest our patient as the risk of another
episode of glaucoma would be unacceptable.
If there is a causal relationship, it could be proposed that
Citalopram may directly act on the iris or ciliary body
muscle through serotonergic or cholinergic mechanisms
or both.
We think our case demonstrates that the need to prescribe
Citalopram and other SSRI with caution, especially in
older female patients, anatomically predisposed individu-
als, glaucoma patients and those with a family history of
glaucoma. We would like to suggest that careful consider-
ation should be given to include history taking and fun-
doscopic examination before and after starting SSRI in
depressed patients.
We think this area merits further investigation and col-
leagues should continue to report cases of glaucoma or
raised IOP to relevant Drugs safety committees.
Abbreviations
SSRI – Selective serotonin reuptake inhibitor
5-HT-5-Hydroxytriptyamine
Publish with BioMed Central and every
scientist can read your work free of charge
"BioMed Central will be the most significant development for
disseminating the results of biomedical research in our lifetime."
Sir Paul Nurse, Cancer Research UK
Your research papers will be:
available free of charge to the entire biomedical community
peer reviewed and published immediately upon acceptance
cited in PubMed and archived on PubMed Central
yours — you keep the copyright
Submit your manuscript here:
http://www.biomedcentral.com/info/publishing_adv.asp
BioMedcentral
BMC Ophthalmology 2005, 5:23 http://www.biomedcentral.com/1471-2415/5/23
Page 4 of 4
(page number not for citation purposes)
IOP – Intra ocular pressure
Competing interests
RC – None
SH – None
JDRD – None
ST-Has been sponsored to attend meetings by Astra
Zeneca, Sanofi-synthelabo, Eli-Lilly, Pfizer, Novartis and
Wyeth pharmaceuticals.
Authors' contributions
RC-participated in information gathering, literature
search, data analysis, drafting and co-ordination of the
case report. SH-Participated by managing the patients
ophthalmologic problems and helped to draft the manu-
script. JDRD-Involvement in the psychiatric management,
co-ordination of the work and co-wrote the Manuscript.
ST-conceived the idea, participated in information gather-
ing, literature search, data analysis, and psychiatric man-
agement of the case and drafting the final manuscript. All
authors read and approved the final manuscript.
Acknowledgements
Written consent was obtained from the patient for the publication of the
patient's details.
References
1. Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshelman
S, Wittchen H, Kendler KS: Lifetime and 12 month prevalence
of DSM-3R psychiatric disorders in the united states. Archives
of General Psychiatry 1994, 51:8-19.
2. Lonquist J, Sutonen H, Syvalahti E, Appleberg B, Koskinen T,
Maninikko T, Mehtones OP, Narala M, Shiro S, Auvinen J: Antide-
pressant efficacy and quality of life in Depression: A double
blind study with moclobomide and Fluoxetine. Acta Psychiatrica
Scandinavia 1994, 89(6):363-9.
3. Stokes PE: Fluoxetine: A five-year review. clinical therapeutics
1993, 15(2):216-43.
4. Nemeroff CB: Paroxetine: An overview of the efficacy and
safety of a new selective reuptake inhibitor in the treatment
of depression. Journal of clinical Psychopharmacology 1993, 13(suppl
2):10S-17S.
5. Birley M, Moret C: Neurological mechanisms involved in anti-
depressant therapies. Clin Neuropharmacol 1993, 16:387-400.
6. Barrett NL, Osbourne NN: The presence of serotonin (5-HT1)
receptors negatively coupled to adenylate cyclase in rabbit
and human iris-Ciliary processes. Exp Eye Res 1993, 57:209-16.
7. Osbourne NN, Tobin AB: Serotonin accumulating cells in the
iris-Ciliary body and cornea of various species. Exp Eye Res
1987, 44:731-46.
8. Osbourne NN: Serotonin and melatonin in the iris/ ciliary
processes and their involvement in intraocular presence.
Acta Neurobiol Exp 1994, 54(Suppl):57-64.
9. Costagliola C, Mastropasqua L, Streado L: Fluoxetine oral admin-
istration increases intraocular pressure. Br J Opthalmol 1996,
80:678.
10. Costagliola C, Inliano G, Rinaldi M: Effect of topical of Ketanserin
administration on intra-ocular pressure. Br J Ophthalmol 1993,
77:344-8.
11. Tripathi RC, Tripathi BJ, Haggerty C: Drug – induced glaucoma's:
mechanisms and management. Drugs safety 2003,
26(11):749-767.
12. Quigley HA: Number of people with glaucoma worldwide. Br
J Opthalmol 1996, 80(5):389-393.
13. Tielsch JM: The epidemiology and control of open angle glau-
coma. A population based perspective. Annu Rev Public Health
1996, 17:121-36.
14. Salmon JF: Predisposing factors for chronic angle-closure glau-
coma. Prog Retin Eye Res 1999, 18(1):121-32.
15. Lowe RF: Amitriptyline and glaucoma. Med J Aust 1966,
2:509-510.
16. Ritch R, Krupin T, Henry C, Kurata F: Oral imipramine and acute
angle closure glaucoma. Arch Ophthalmol 1994, 112:67-68.
17. Bradley NG, Sanbrook MC, Malourf AJ, Agarwal SA: Venlafaxine
and bilateral acute closure glaucoma. Med J Aust 2002,
4;176(5):241.
18. Eke T, Bates AK: Acute angle closure glaucoma associated
with Paroxetine (letter). BMJ 1997, 314:1387.
19. Kadoi C, Hayasaka S, Tsukamoto E, Matsumoto M, Hayasaka Y,
Nagaki Y: Bilateral angle closure glaucoma and visual loss pre-
cipitated by antidepressant and ant anxiety agents in a
patient with depression. Opthalmologica 2000, 214:360-361.
20. Ahmad S: Fluoxetine and glaucoma (letter). Drug intell clin Pharm
1991, 25(4):436.
21. Eke T, Carr S: Acute glaucoma, chronic glaucoma and sero-
tonergic drugs. Br J Ophthalmol 1998, 82:976-979.
Pre-publication history
The pre-publication history for this paper can be accessed
here:
http://www.biomedcentral.com/1471-2415/5/23/prepub
