LETTER TO THE EDITOR

Esomeprazole-induced irritability

Asuman Celikbilek • Mehmet Celikbilek •

Lutfi Akyol • Ilyas Pirti

Received: 17 June 2013 / Accepted: 17 July 2013

� Belgian Neurological Society 2013

Dear Editor,

Irritability is one of the main moods of humans. It is a

behavioral manifestation of easy annoyance, touchiness

and is characterized by emotion of anger and temper out-

bursts [1]. Esomeprazole, which is the last member of

proton-pump inhibitors (PPIs) presented to the market, is

used to treat gastrooesophageal reflux, gastritis, and peptic

ulcer diseases. Some primary adverse effects have been

reported with PPIs like headache, diarrhea, constipation,

nausea, and rash. Secondary adverse effects, such as bone

fractures, enteric infections, and hypomagnesaemia may

also occur with long-term use of PPIs. Methotrexate and

clopidogrel were known to cause drug–drug interactions

with the concomitant use of esomeprazole [2, 3]. Accord-

ing to our knowledge, there is not any reported case of

irritability that is induced by the use of esomeprazole in

combination with citalopram.

A 27-year-old female patient was admitted to our out-

patient clinic with complaints of heartburn and dyspepsia

with a history of 2 months. The physical examination of

the patient was normal except for epigastric tenderness.

Laboratory test results were within normal range. She has

taken a selective serotonin reuptake inhibitor (SSRI)

named citalopram for minor depression for 2 years. Upper

endoscopic examination was performed and the non-ero-

sive gastritis with a negative rapid urease test was detected.

Esomeprazole treatment was started 40 mg per day. At the

second day; nervousness, touchiness, temper outbursts with

aggressive behavior have occurred. She has begun to face

problems somehow with her relatives. Though her symp-

toms have worsened during this course, she has persisted

on treatment. After 1 month, her reflux symptoms and

dyspeptic complaints have been fully diminished whereas

her irritability was to gradually increase. She has tested her

symptoms to have a break in drug use for a week, but her

reflux symptoms have begun to reappear while her irrita-

bility was to decline. The laboratory tests, including elec-

trolytes were still normal on her second admission. Irritable

mood during the treatment with esomeprazole was con-

firmed by psychiatric evaluation. Thereupon, her treatment

was changed to rabeprazole with complete healing, but not

any side effect.

Although irritability may occur due to the hypomag-

nesaemia and/or hypokalemia during the use of esomep-

razole [4], repeated measures revealed no aberrant levels

for both electrolytes in our patient. In this patient, irrita-

bility might occur in several ways. First, irritability has

been recently reported in some lysosomal enzyme defi-

ciency syndromes as causing lysosomal enzyme inhibition

with PPIs by Liu et al. [5]. Second, anti-acid drugs could

change the plasma concentration of SSRIs via changing

gastric pH [6]. Third, citalopram is metabolized by cyto-

chrome P450 (CYP) 3A4, 2C19 and 2D6 in which both of

CYP2C19 and CYP3A4 are also used for biotransforma-

tion of esomeprazole in the liver [7]. This suggests

that pharmacokinetic interactions might occur between

esomeprazole and citalopram. Fourth, esomeprazole is a

substrate—an inhibitor—for P-glycoprotein [8]. Although

A. Celikbilek

Department of Neurology, Bozok University,

Medical School, Yozgat, Turkey

M. Celikbilek (&)

Department of Gastroenterology, Bozok University,

Medical School, Yozgat, Turkey

e-mail: drcelikbilek@yahoo.com

L. Akyol � I. Pirti

Department of Internal Medicine, Bozok University,

Medical School, Yozgat, Turkey

123

Acta Neurol Belg

DOI 10.1007/s13760-013-0236-0

we did not measure the plasma concentration of the

citalopram, we can speculate that esomeprazole, by

inhibiting the P-glycoprotein, might reduce the plasma

concentrations of some drugs such as SSRIs and may cause

irritable mood as in our patient.

In this case, adverse drug reaction probability score was

5 [9]. Drug interaction probability score was also calcu-

lated and found 5 as probable category [10]. The physician

should be alert about this behavioral change to ensure

accurate therapeutic efficiency with patient satisfaction.

Herein, for the first time, it is noticeable that irritability

may occur due to interaction between esomeprazole and

citalopram.

Conflict of interest None.

References

1. Stringaris A (2011) Irritability in children and adolescents: a

challenge for DSM-5. Eur Child Adolesc Psychiatry 20(2):61–66

2. Bezabeh S, Mackey AC, Kluetz P, Jappar D, Korvick J (2012)

Accumulating evidence for a drug–drug interaction between

methotrexate and proton pump inhibitors. Oncologist 17(4):

550–554

3. Ohbuchi M, Noguchi K, Kawamura A, Usui T (2012) Different

effects of proton pump inhibitors and famotidine on the clopi-

dogrel metabolic activation by recombinant CYP2B6, CYP2C19

and CYP3A4. Xenobiotica 42(7):633–640

4. Negri AL, Valle EE (2011) Hypomagnesaemia/hypokalemia

associated with the use of esomeprazole. Curr Drug Saf 6(3):

204–206

5. Liu W, Baker SS, Trinidad J, Burlingame AL, Baker RD, Forte JG

et al. (2013) Inhibition of lysosomal enzyme activities by proton

pump inhibitors. J Gastroenterol Mar 12 [Epub ahead of print]

6. Montastruc F, Sommet A, Bondon-Guitton E, Durrieu G, Bui E,

Bagheri H et al (2012) The importance of drug–drug interactions

as a cause of adverse drug reactions: a pharmacovigilance study

of serotoninergic reuptake inhibitors in France. Eur J Clin Phar-

macol 68(5):767–775

7. Holmgren P, Carlsson B, Zackrisson AL, Lindblom B, Dahl ML,

Scordo MG et al (2004) Enantioselective analysis of citalopram

and its metabolites in postmortem blood and genotyping for

CYD2D6 and CYP2C19. J Anal Toxicol 28(2):94–104

8. Pauli-Magnus C, Rekersbrink S, Klotz U, Fromm MF (2001)

Interaction of omeprazole, lansoprazole and pantoprazole with

P-glycoprotein. Naunyn Schmiedebergs Arch Pharmacol 364(6):

551–557

9. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA

et al (1981) A method for estimating the probability of adverse

drug reactions. Clin Pharmacol Ther 30(2):239–245

10. Horn JR, Hansten PD, Chan LN (2007) Proposal for a new tool

to evaluate drug interaction cases. Ann Pharmacother 41(4):

674–680

Acta Neurol Belg

123