Correspondence

Hyponatremia Associated with Escitalopram

N Engl J Med 2007; 356:94-95January 4, 2007

Article

To the Editor:

There are numerous reports of hyponatremia associated with selective serotonin-reuptake inhibitors (SSRIs),1 with at least 35 reports involving citalopram (Celexar, Forest).2 However, there have been few reported cases of hyponatremia associated with escitalopram (Lexapro, Forest),2 making it difficult to confirm the association. We report another case of hyponatremia in a patient receiving escitalopram.

A 75-year-old woman presented to the emergency room with confusion. Her medical history included hypertension and depression; she was receiving amlodipine, hydrochlorothiazide, alprazolam, aspirin, and esomeprazole at home. A computed tomographic scan of the head obtained in the emergency room showed mild atrophy but was otherwise normal. The results of laboratory tests included a serum sodium concentration of 129 mmol per liter. Magnetic resonance imaging of the brain showed moderate small-vessel disease and intracranial distal vascular disease, with no evidence of high-grade stenosis, a mass, acute infarction, or a subdural hematoma. The next day, the patient's serum sodium concentration was 133 mmol per liter, a value that varied only slightly over a period of 6 days. On day 7, escitalopram was prescribed, and donepezil (Aricept, Pfizer) was prescribed on day 8. Five days later, the patient's serum sodium concentration was 116 mmol per liter. Serum osmolality was 250 mOsm per kilogram of water, urinary osmolality was 318 mOsm per kilogram of water, and the urinary sodium concentration was 106 mmol per liter. The escitalopram was discontinued, and the serum sodium concentration rose to 139 mmol per liter over a period of 5 days.

Hyponatremia is a known adverse effect of the SSRIs.1 The risk of hyponatremia is reported to be three times as high in patients taking SSRIs as in patients taking other antidepressants.3 The risk of hyponatremia is highest during the first weeks of treatment; it is higher in women than in men and in persons 65 years of age or older than in younger persons.3 Patients receiving multiple medications known to cause hyponatremia may also be at increased risk. The package insert for donepezil says that this drug has been associated with hyponatremia only in rare, voluntary post-marketing reports and that there are inadequate data to determine a causal relationship.4 In this case, the Naranjo Inventory (a tool used to estimate the probability of an adverse drug reaction) indicated that escitalopram probably caused the hyponatremia.5

SSRI-induced hyponatremia is attributed to a syndrome of inappropriate antidiuretic hormone secretion induced by a nonosmotic release of antidiuretic hormone.1 The syndrome of inappropriate antidiuretic hormone secretion is characterized by a low serum sodium concentration (<135 mmol per liter), urinary osmolality exceeding 200 mOsm per kilogram, a urinary sodium concentration exceeding 20 mmol per liter, and serum osmolality of less than 280 mOsm per kilogram.1 Since escitalopram is the S-enantiomer of citalopram, the active moiety in citalopram may be the cause of the hyponatremia.2 More data are needed to prove an association between hyponatremia and escitalopram.

Jill A. Covyeou, Pharm.D.
Ferris State University College of Pharmacy, Essexville, MI 48732
jill.covyeou@bhsnet.org

Cherry W. Jackson, Pharm.D.
Auburn University School of Pharmacy, Birmingham, AL 35203

5 References

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   Aricept. Teaneck, NJ: Eisai, 2005 (package insert). (Accessed December 13, 2006, at http://www.aricept.com/content/pi.pdf.)
   

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   Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-245
   CrossRef | Web of Science | Medline

Citing Articles (8)

Citing Articles

1. 1

   Po-Hsin Tsai, Hsi-Chung Chen, Shih-Cheng Liao, Mei-Chih Meg Tseng, Ming-Been Lee. (2012) Recurrent escitalopram-induced hyponatremia in an elderly woman with dementia with Lewy bodies. General Hospital Psychiatry 34:1, 101.e5-101.e7
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2. 2

   Edoardo Spina, Gianluca Trifirò, Filippo Caraci. (2012) Clinically Significant Drug Interactions with Newer Antidepressants. CNS Drugs 26:1, 39-67
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3. 3

   Guang Yang, Hai-Zhi Bu. 2011. Toxicology of Chiral Drugs. , 381-399.
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   Gul Yalcin-Cakmakli, Kader Karli Oguz, Ali Shorbagi, Demet Funda Bas, Begum Ergan-Arsava, Mahir Kunt, Mehmet Akif Topcuoglu. (2010) Hyponatremic Encephalopathy after Excessive Water Ingestion Prior to Pelvic Ultrasound: Neuroimaging Findings. Internal Medicine 49:16, 1807-1811
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5. 5

   S. W. Smith. (2009) Chiral Toxicology: It's the Same Thing...Only Different. Toxicological Sciences 110:1, 4-30
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6. 6

   Pasquale Esposito, Teresa Rampino, Antonio Dal Canton. (2008) In Reply to ‘A Possible Mechanism for Severe Symptomatic Hyponatremia During Sibutramine Therapy’. American Journal of Kidney Diseases 52:6, 1198
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7. 7

   W. Stephen Waring, Julie A. Gray, Ann Graham. (2008) Predictive factors for generalized seizures after deliberate citalopram overdose. British Journal of Clinical Pharmacology 66:6, 861-865
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8. 8

   (2007) Current awareness: Pharmacoepidemiology and drug safety. Pharmacoepidemiology and Drug Safety 16:8, i-xii
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