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Reversible Hyponatremia and Venlafaxine

TO THE EDITOR: I present a case of reversible hyponatremia with venlafaxine in which the patient’s serum sodium level decreased from 132 mmol/liter to 122 mmol/liter after 1 week of therapy. After discontinuation of venlafaxine, her serum sodium level increased to 130 mmol/liter within 1 week.

Case Report

Ms. A was a 75-year-old woman with a history of nonsmall cell lung carcinoma with brain metastasis. She had received combination therapy with chemotherapy and cranial radiation. Six months after her diagnosis, she developed depression. One week before hospital admission, she was administered extended-release venlafaxine, 37.5 mg/day. Her serum sodium level was 132 mmol/liter. Over the next week, she developed cognitive impairment with lethargy and was admitted to the hospital. Magnetic resonance imaging of her brain showed decreased size of her frontal lobe lesion. The results of laboratory studies included a sodium level of 122 mmol/liter, a potassium level of 3.7 mmol/liter, a calcium level of 9.1 mmol/liter, an albumin level of 3.3 g/dl, a BUN level of 13 mg/dl, and a creatinine level of 0.4 mg/dl. Serum and urine osmolalities were not obtained.

A psychiatric consultation-liaison service examination on hospital day 2 revealed a blunted affect, no suicidal ideations, no psychosis, and a Mini-Mental State Examination score of 20. Ms. A’s diagnoses were delirium (rule out syndrome of inappropriate antidiuretic hormone secretion) and depressive disorder not otherwise specified. Venlafaxine was discontinued; Ms. A’s electrolyte levels and brain volume status were monitored closely. Her level of consciousness and cognitive function gradually improved. She was discharged on hospital day 5, when her serum sodium level was 126 mmol/liter. Six days after venlafaxine was discontinued, her serum sodium level was 130 mmol/liter, and her cognition had returned to baseline functioning.

Discussion

Euvolemic hypo-osmolar hyponatremia from the syndrome of inappropriate antidiuretic hormone secretion is associated with various systemic factors (e.g., increased age, malignancy, pulmonary disease, and CNS lesions) and may be medication-induced (e.g., thiazide diuretics, vincristine, cyclophosphamide, and chlorpropamide).¹ Patients may develop delirium. A clinical evaluation reveals hyponatremia, normal BUN and creatinine levels, a normal volume status, decreased serum osmolality, and increased urine osmolality.¹ If sodium levels are 120–134 mmol/liter, reversal of the provocative stimulus, fluid restriction, consideration of a loop diuretic and/or intravenous normal saline, and monitoring of electrolyte and fluid status may suffice.¹ More severe hyponatremia may require cautious administration of intravenous hypertonic saline, a loop diuretic, and correction of associated hypokalemia and hypomagnesemia.¹ Excessively rapid correction of severe hyponatremia may result in central pontine myelinosis.¹

Many psychotropic medications have been associated with hyponatremia (e.g., selective serotonin reuptake inhibitors [SSRIs], venlafaxine, trazodone, nefazodone, reboxetine, mirtazepine, amoxapine, maprotiline, bupropion, carbamazepine, phenothiazines, tricyclic antidepressants, and monamine oxidase inhibitors).^1,2 Although less frequently reported than with SSRIs, there have been reports of hyponatremia with venlafaxine.^3–6 This risk may be associated with venlafaxine’s SSRI-like properties.⁷

Kirby et al.,³ in a retrospective study, found hyponatremia in 39% of elderly psychiatric patients receiving an SSRI or venlafaxine versus 10% in comparison subjects. Of their study cohort, 10 of the 14 venlafaxine patients had hyponatremia. Boyd⁴ reported 15 cases of venlafaxine-associated hyponatremia to the Adverse Drug Reactions Advisory Committee in Australia; sodium values ranged from 116–130 mmol/liter, with a mean of 124 mmol/liter. There have been additional reports of venlafaxine-associated hyponatremia.^5,6 Notably, the patient reported by Roxanas⁶ experienced yet another episode of hyponatremia when she was subsequently exposed to mirtazepine, which also acts through a serotonergic mechanism.

In Ms. A’s case, there is some question as to whether venlafaxine was solely responsible for her hyponatremia. Her history of nonsmall cell lung cancer may have predisposed her to the syndrome of inappropriate antidiuretic hormone secretion because of a tumor-related paraneoplastic syndrome. Her CNS metastatic disease could also have had a similar predisposing effect. In addition, certain confirmatory laboratory studies demonstrating decreased serum osmolality and increased urine osmolality in the syndrome of inappropriate antidiuretic hormone secretion were not obtained.¹ Nonetheless, the sequence of clinical events supports a causal relationship between venlafaxine and hyponatremia. The precipitous drop in Ms. A’s serum sodium level within 1 week of venlafaxine initiation and a similarly brisk return toward eunatremia after its discontinuation were associated with the onset and later resolution of her delirium.

When prescribing antidepressants for elderly and medically ill patients, physicians are alerted to the possibility of SSRI- or venlafaxine-associated hyponatremia and to monitor pretreatment and posttreatment sodium levels. Patients treated with venlafaxine who have mental status changes need prompt assessment of fluid and electrolyte status. Patients already at risk of the syndrome of inappropriate antidiuretic hormone secretion because of cancer and/or CNS disease should be managed with particular caution.

REFERENCES

1. Buff DD, Markowitz S: Hyponatremia in the psychiatric population: a review of diagnostic and management strategies. Psychiatr Ann 2003; 33:318–325
2. Bugunovic OJ, Sotelo J, Madhusoodanan S: Hyponatremia secondary to antidepressants. Psychiatr Ann 2003; 33:333–339
3. Kirby D, Harrigan S, Ames D: Hyponatremia in elderly psychiatric patients treated with selective serotonin reuptake inhibitors and venlafaxine: a retrospective controlled study in an inpatient unit. Int J Geriatr Psychiatry 2002; 17:231–237[CrossRef][Medline]
4. Boyd IW: Comment: hyponatremia with venlafaxine. Ann Pharmacother 1998; 32:981[CrossRef][Medline]
5. Masood GR, Karki SD, Patterson WR: Hyponatremia with venlafaxine. Ann Pharmacother 1998; 32:49–50[Abstract/Free Full Text]
6. Roxanas MG: Mirtazepine-induced hyponatraemia. Med J Aust 2003; 179:453–454
7. Morton WA, Sonne SC, Verga MA: Venlafaxine: a structurally unique and novel antidepressant. Ann Pharmacother 1995; 29:387–395[Abstract]

Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Email this article to a Colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via Google Scholar Articles by Bourgeois, J. A. Search for Related Content PubMed Citation Articles by Bourgeois, J. A. Depression Delirium Antidepressants

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