Correspondence
Reboxetine and Hyponatremia
N Engl J Med 2000; 342:215-216January 20, 2000
- Article
To the Editor:
Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone are known side effects of selective serotonin-reuptake inhibitors such as fluoxetine and sertraline1,2 and the inhibitor of serotonin and norepinephrine reuptake venlafaxine.3 We describe the occurrence of hyponatremia in a patient treated with reboxetine, a new antidepressant drug that is a norepinephrine-reuptake inhibitor. The patient was a 72-year-old man who was hospitalized for rehabilitation for mild left hemiparesis caused by a stroke three months earlier and for treatment of severe depressive symptoms, including depressed mood, feelings of worthlessness, and recurrent thoughts of death that had begun after the stroke. His medical history included diabetes mellitus, hypertensive and ischemic cardiomyopathy, and degenerative joint disease.
At the time of admission, he was receiving aspirin (0.1 g daily), enalapril (20 mg daily), and glyburide (glibenclamide, 5.0 mg daily). On the third day of hospitalization, he was given 4 mg of reboxetine for treatment of his depression. His serum sodium concentration was 133 mmol per liter (normal range, 134 to 146) on the day reboxetine was begun and 126 mmol per liter five days later. After eight days of reboxetine therapy, the patient reported malaise and nausea. His weight and fluid intake had not changed. At this time his serum sodium concentration was 118 mmol per liter, his urine sodium concentration was 181 mmol per liter, his serum osmolality was 266 mOsm per kilogram, and his urine osmolality was 430 mOsm per kilogram. The reboxetine was discontinued.
In the next six days, the patient's symptoms disappeared, and his serum sodium concentration returned to normal. After an additional seven days, at which time his serum sodium concentration was 132 mmol per liter, the patient was given the same dose of reboxetine for six days (after he provided informed consent). Six days later, nausea, asthenia, and hyponatremia (serum sodium concentration, 121 mmol per liter) reappeared; again, the symptoms disappeared after the drug was discontinued.
This course of events suggests that the patient's hyponatremia was related to reboxetine therapy and was due to the inappropriate secretion of antidiuretic hormone. None of the other possible causes of hyponatremia, including diuretic therapy, tumors, respiratory diseases, and acute central nervous system diseases, were present.4
Reboxetine should be added to the list of drugs that can cause hyponatremia. From a clinical point of view, we suggest that serum sodium be measured periodically in elderly patients who are taking this drug.
4 ReferencesPiera Ranieri, M.D.
Simone Franzoni, M.D.
P. Richiedei Hospital, 25064 Gussago, ItalyMarco Trabucchi, M.D.
Geriatric Research Group, 25122 Brescia, Italy1
Bouman WP ,Pinner G ,Johnson H . Incidence of selective serotonin reuptake inhibitor (SSRI) induced hyponatraemia due to the syndrome of inappropriate antidiuretic hormone (SIADH) secretion in the elderly. IntJ Geriatr Psychiatry 1998;13:12-15
CrossRef | Web of Science | Medline2
Jackson C ,Carson W ,Markowitz J ,Mintzer J . SIADH associated with fluoxetine and sertraline therapy. Am J Psychiatry 1995;152:809-810
Web of Science | Medline3
Ranieri P ,Franzoni S ,Rozzini R ,Trabucchi M . Venlafaxine-induced reset osmostat syndrome: case of a 79-year-old depressed woman. J Geriatr Psychiatry Neurol 1997;10:75-78
Web of Science | Medline4
Singer GG, Brenner BM. Fluid and electrolyte disturbances. In: Fauci AS, Martin JB, Braunwald E, et al., eds. Harrison's principles of internal medicine. 14th ed. Vol. 1. New York: McGraw-Hill, 1998:268-9.
Author/Editor Response
The above letter was referred to Pharmacia & Upjohn, the manufacturer of reboxetine, which offers the following reply:
To The Editor: Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone have been reported in patients treated with serotonergic drugs,1,2 and a recent review of post-marketing surveillance information yielded a total of 736 cases of hyponatremia among patients taking serotonin-reuptake inhibitors. Fluoxetine was involved in 75 percent of the cases, paroxetine in 12 percent, and sertraline in 12 percent.3 Reboxetine, a selective norepinephrine-reuptake inhibitor, has been studied in more than 1622 patients in clinical trials, 347 of whom were older than 65 years of age. There were no reports of any cases of hyponatremia in the clinical-trial data base. A review of reports to the company showed that three patients may have had the syndrome. The limited amount of information available to us makes it difficult to determine the exact relation between reboxetine and the syndrome, given that those patients had several illnesses and were receiving more than one medication.
3 ReferencesGerri E. Schwartz, Ph.D.
Pharmacia & Upjohn, Bridgewater, NJ 08807Joachim Veith, M.D.
Pharmacia & Upjohn, Kalamazoo, MI 490011
Pillans PI ,Coulter DM . Fluoxetine and hyponatraemia -- a potential hazard in the elderly. N Z Med J 1994;107:85-86
Medline2
Strachan J ,Shepherd J . Hyponatraemia associated with the use of selective serotonin re-uptake inhibitors. Aust N Z J Psychiatry 1998;32:295-298
CrossRef | Web of Science | Medline3
Liu BA ,Mittmann N ,Knowles SR ,Shear NH . Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone associated with the use of selective serotonin reuptake inhibitors: a review of spontaneous reports. CMAJ 1996;155:519-527[Erratum, CMAJ 1996;155:1043.]
Web of Science | Medline
- Citing Articles (5)
Citing Articles
1
Tanvir Singh. (2007) Atomoxetine-induced hyponatremia. Australian and New Zealand Journal of Psychiatry 41:5, 458-458
CrossRef2
C Egger, M Muehlbacher, M Nickel, C Geretsegger, C Stuppaeck. (2006) A review on hyponatremia associated with SSRIs, reboxetine and venlafaxine. International Journal of Psychiatry in Clinical Practice 10:1, 17-26
CrossRef3
2006. Reboxetine. , 3028-3029.
CrossRef4
(2000) Current Awareness. Pharmacoepidemiology and Drug Safety 9:4, 341-356
CrossRef5
&NA;. (2000) Reboxetine. Reactions Weekly &NA;:786, 10
CrossRef
