Ms. K. is a 65-year-old woman with hypertension and dyslipidemia currently taking hydrochlorothiazide 12.5 mg daily and simvastatin 20 mg daily with excellent control of both conditions. She presents to her nurse practitioner (NP) with an increased feeling of hopelessness and sadness. Upon careful clinical evaluation, the NP diagnoses a new onset major depressive disorder and prescribes a selective serotonin reuptake inhibitor (SSRI) at a recommended initial dose. The patient is advised to schedule a follow-up appointment in 4 weeks or return sooner if her symptoms worsen. She was also informed that relatively little antidepressant effect would be noticed during the first few weeks of use and was referred for counseling.
During the first 2 weeks of the SSRI use, the patient tolerated the medication with the exception of a slightly dry mouth, corrected with increased fluid intake, and mild gastrointestinal upset, corrected by taking the medication with food. These potential adverse effects were discussed during the office visit.
[black small square] The Follow-up Visit
When Ms. K. returned 4 weeks later, she complained of a 6-day history of progressively worsening anorexia, nausea, fatigue, frontal headache, and "not feeling right." She was accompanied by her daughter who mentioned that her mother was a "bit confused at times" over the past 2 days. Physical examination results did not contribute to the diagnosis with the exception of blunted affect and fatigued appearance. Serum electrolytes were analyzed during the evaluation of her new symptoms. In contrast to normal electrolytes obtained about 2 months prior to initiating the SSRI, her current sodium level of 122 mEq/L was reported. Remaining chemistry and hematologic parameters were within normal limits. Evaluation for urinary tract infection was negative.
[black small square] Hyponatremia
Serum sodium concentration and serum osmolarity normally are maintained under precise control by homeostatic mechanisms involving stimulation of thirst, secretion of antidiuretic hormone, and renal handling of filtered sodium. Hyponatremia is the most common electrolyte problem seen in both inpatient and outpatient settings.1 Hyponatremia is also a known adverse effect of SSRI use.2-4 The normal serum sodium level range is 135 to 145 mEq/L,(or in international units, 135 to145 mmol/L) Hyponatremia is a sodium level less than 135 mEq/L (less than 135 mmol/L).
It is important to know what places a patient at risk for SSRI-induced hyponatremia. Data reported to the Food and Drug Administration revealed emerging risk factors such as female gender, age older than 65 years, and early SSRI use, with greatest risk noted in the first weeks of treatment. Another significant risk is the use of an SSRI along with additional medication(s) that can deplete sodium including the thiazide and loop diuretics.1-3 From the results of a number of prospective studies on SSRI-induced hyponatremia, its incidence varies from 0.5% to 32%.2
[black small square] Causes
The cause of SSRI-induced hyponatremia is likely due in part to the drug's ability to trigger a syndrome of inappropriate antidiuretic hormone (SIADH) secretion induced by a nonosmotic release of antidiuretic hormone.2,4 Besides low serum sodium, other abnormal laboratory parameters during SIADH include urinary osmolality exceeding 200 mOsm/kg, a urinary sodium concentration exceeding 20 mmol/L, and serum osmolality of less than 280 mOsm per kilogram. Another risk is advancing age due to the aging kidney's reduced ability to conserve sodium, particularly when stressed.4 As seen with Ms. K., patients who have recently started taking an SSRI often report increased fluid intake to counteract dry mouth.
Additional evaluation for SSRI-induced hyponatremia includes assessment for other common reasons for change in mental status. In more severe cases, neuroimaging is indicated; a commonly reported finding is small lateral ventricles consistent with cerebral edema.1 Regardless of the cause, hyponatremia can lead to death due to severe cerebral edema that can result in brain stem herniation or status epilepticus, the latter usually noted with severe deficiency when serum sodium is less than 110 mEq/L. In general, if the sodium falls slowly, as likely happens with SSRI-induced hyponatremia, symptoms are milder and the condition better tolerated in comparison to rapid onset (over 24 to 48 hours) disease where a relatively mild hyponatremia can cause severe symptoms.1
Treatment of SSRI-induced hypotonic hyponatremia without evidence of disturbed circulation volumes includes water restriction and mild diuresis with a loop diuretic. More severe cases are typically treated with higher doses of loop diuretics and hypertonic saline.1 Ms. K. was briefly hospitalized. The SSRI was discontinued. No further hyponatremia was noted. Her depression was treated with counseling and supportive care; no psychotropic medication was used due to the patient's concern of recurring hyponatremia, which has been reported with the use of numerous other psychotropic medications.3
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