A Case of SSRI-Induced Hyponatremia
Kip A. Corrington, MD,
[J Am Board Fam Pract 15(1):63-65, 2002. © 2002 American Board of Family Practice]
Hyponatremia complicates 1% of hospital admissions and can be associated with serious central nervous system effects. We report a case of a 38-year-old woman with hyponatremia resulting in seizures and coma. Medications are one of many causes of hyponatremia. This case emphasizes the need to consider selective serotonin reuptake inhibitors (SSRIs) as a potential source of hyponatremia in all age groups.
An unresponsive 38-year-old woman with a history of schizophrenia, depression, and tobacco abuse was transported by Emergency Medical Transport to the emergency department of a large community hospital after suffering an apparent generalized tonic-clonic seizure, which was witnessed by her family at home. For 2 to 3 days before the seizure, the family reported the patient complained of fatigue, nausea, and intermittent emesis.
Approximately 30 days earlier, the patient had started taking paroxetine (Paxil) for depression and trimethoprim-sulfamethoxazole (Septra) for bronchitis. The patient's medication regimen before admission also included risperidone (Risperdal), ibuprofen, and an albuterol inhaler.
Cerebral spinal fluid, urine, and blood cultures were negative. The patient's serum sodium level slowly returned to normal within 36 hours, and the phenytoin was discontinued without any further seizure activity. She was extubated, her cognitive function returned to baseline, and she continued to maintain normal sodium levels with the discontinuation of her paroxetine.
Brief Literature Search
Although some articles reported possible alternative explanations for the hyponatremia, many reported a strong temporal association between SSRI use and hyponatremia, a lack of an alternative explanation, and reversal of the process with discontinuation of the SSRI, suggesting a causal relation. The literature reviewed rated a definite or probable causal link in 40% of the cases. The remainder of the cases showed a probable causal link between SSRI use and hyponatremia. The findings of this case report have been reported to the pharmaceutical company and the Food and Drug Administration.
The correction of the patient's hyponatremia, combined with the discontinuation of her paroxetine, resulted in resolution, without recurrence, of her hyponatremia and the elimination of seizure activity. A literature search found a strong association between SSRI use and hyponatremia, with the annual incidence of hyponatremia in patients using paroxetine at 3.5/1,000. Alternative explanations are possible, but the most probable cause of the altered electrolyte status in this patient was SSRI use. Although risperidone also can cause decreased sodium levels, that the hyponatremia did not recur after restarting the risperidone makes a stronger case for paroxetine as the offending agent. Most cases of SSRI-induced hyponatremia involve the elderly, which could be related to altered antidiuretic hormone regulation or action of the antidiuretic hormone on the kidneys. Impairment of the maximal diluting and concentrating ability of the kidney[2,3] and increased antidiuretic hormone secretion might contribute as well. Another possible explanation for the propensity for hyponatremia in the elderly is their increased antidiuretic hormone response to osmolar stimuli compared with young control patients.
This case of hyponatremia in a young woman raises the question of what factors might predispose a younger patient to SSRI-induced hyponatremia? Additive drug effects and drug interactions are two potential sources. Dopamine antagonists, such as haloperidol and domperidone, have been shown in animal models to increase thirst and to facilitate antidiuretic hormone secretion.[5-7] Diuretics are thought to predispose patients to hyponatremia. SSRIs inhibit a number of cytochrome P-450 isoenzymes. Through inhibition of the metabolism of drugs used concomitantly, such as neuroleptics, SSRIs might increase the effect of these other drugs on water and electrolyte balance. Certain disease processes might also predispose patients to hyponatremia, including such pulmonary processes as pneumonia, malignant neoplasms, and psychiatric conditions, such as schizophrenia.
SSRI use should be considered in the differential diagnosis of hyponatremia. Hyponatremia can complicate SSRI use in the young as well as the older patient, especially if other risk factors are present. In the case described, the patient had multiple concurrent risk factors. Clinicians should be alert for SSRI-induced hyponatremia, not only in the elderly patient, but also in the younger patient, particularly if the onset of symptoms has a close temporal association with the start of SSRI treatment.
Submitted, revised, 26 March 2001.
Address reprint requests to Karl B. Fields, MD, Family Medicine Residency Program, Moses Cone Health System, 1125 N. Church St., Greensboro, NC 27401-1007.