A Possible Mechanism for Severe Symptomatic Hyponatremia During Sibutramine Therapy

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To the Editor:

We read with great interest the case report by Esposito et al¹ describing a case of life-threatening hyponatremia associated with sibutramine use in an obese woman. Sibutramine is an inhibitor of the reuptake of serotonin and norepinephrine. The authors hypothesize that this effect of sibutramine on neurotransmitters may induce antidiuretic hormone (ADH) secretion, leading to syndrome of inappropriate ADH secretion and, consequently, hyponatremia. Serum ADH levels were not determined.

Recently, our group showed in an experimental study² that administration of fluoxetine (another selective serotonin reuptake inhibitor) to rats decreased sodium levels while ADH plasma levels were unchanged, and aquaporin 2 protein abundance and water reabsorption in the inner medullary collecting duct increased, leading us to conclude that a direct effect of fluoxetine in the inner medullary collecting duct could explain, at least in part, the hyponatremia sometimes found after fluoxetine use in humans.

We believe that a similar direct effect of sibutramine on the inner medullary collecting duct may be another hypothesis to explain the case of hyponatremia with sibutramine related by Esposito et al,¹ and this mechanism must be tested in animals.

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Financial Disclosure: None.

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References 

1. Esposito P, Rampino T, Gregorini M, et al. Severe symptomatic hyponatremia during sibutramine therapy: A case report. Am J Kidney Dis. 2008;52:137–139
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2. Moyses ZP, Nakandakari FN, Magaldi AJ. Fluoxetine effect on kidney water reabsorption. Nephrol Dial Transplant. 2008;23:1173–1178
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