CLINICAL 'AND RESEARCH ·REPORT Syndrome of Inappropriate Antidiuretic Hormone (SIADH) in an 80-Year-Old Woman Given Clomipramine Barbara R. Sommer, M.D. The author describes the syndrolne ofi nappropriate antidiuretic bor1none, lvith serUIn sodiu111 decreasing from 137 l1zEq/L to 122 lnEq/L in an 80-year-old WOlnan prescribed clolnipl"Q1nine. Tbe patient's delirium and serum soditl1n lvere slow to nonnalize, prolonging IJer hospital stay and delaying treatlnent ofher depression. (Am] Geriatr Psychiatry 1997; 5:268-269) A lthough tricyclic antidepressants have been known to cause the syndrome of inappropriate antidiuretic hormone (SIADH), 1 there are currently few reports of SIADH in geriatric patients taking tIle antidepressant clomipramine, and these reports describe resolution within 3 days.2--' We describe the case of an SO-year-old woman whose delirium and low serum sodium were slow to normalize even after clomipramine was discontinued. Her symptoms had been interpreted by 11er family as worsening of depression. Mrs. A. was hospitalized for the evaluation and treatment of severe depression. During the previous 2 years, she had lost all motivation, had let long-standing friendships go, and had complained of an exacerbation of chronic nausea, without vomiting, which had been evaluated previously as having no medical etiology. She suffered from anhedonia, guilty feelings, fitful sleep, and anorexia, with a 13-pound weight loss over the previous year. Furthermarc, she was isolative and withdrawn, and she often thought of joining her dead husband in heaven. Attempted antidepressant trials included nortriptyline, fluoxetinc, doxepin, trazodone, sertralinc, and paroxetine. She stated, however, that she would become too anxious to increase these antidepressant nlcdications as prescribed, and dosages were never therapeutic. Methylphenidate 10 mg in the morning, and 5 mg at noon increased her energy but was discontinued when she began to fall. Finally, she was admitted to a local hospital. Adnlission laboratory tests, including a serum sodium of 137 mEq/L and a thyroid-stimulating hornlone (TSH) of 3.83 MID/mt were unremarkable. She was on the following medication regimen at the time of admission: conjugated estrogens, 0.625 mg per day; vitamin B6 , 50 mg per day; metoclopramide, 5 mg tid before meals for relief of nausea; L-thyroxin, 0.05 mg per day; and nefazodone, SO mg qam and 100 mg qhs. The nefazodone was discontinued upon her admission. Because of her previous history of either nonresponse or noncompliance on other tricyclic antidepressants, she was started on clomipramine, with doses up to 75 mg per day. All other medications remained unchanged. Over the ensuing 8 days, the patient was observed by her daughters as even more depressed, iso]ative, and listless, now closing her eyes when they came to visit. The daughters arranged for a transfer and a second opinion. Received August 1, 1996; revised November 26,1996; accepted December 5,1996. From the Stanford University Medical Center, Stanford, CA. Address correspondence to Dr. Sommer, Director, Geriatric Psychiatry Progrnm, Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford CA 94305-5546. Copyright © 1997 American Association for Geriatric Psychiatry 268 VOLUME 5 • NUMBER 3 • SUMMER 1997 Sommer On adnlission to the geriatric psychiatry service, Mrs. A. exhibited waxing and waning lethargy and cognitive impairment, complaining of depression and stating, 'II feel dopey, like someone has given me something to sedate me." Her serum sodium was 122 mEq/L. The clonlipramine was considered the likely culprit because all other medications were either unchanged (e.g., metoclopramide for nausea) or discontinued at the other hospital (e.g., nefazodone). Head CT scan, chest X-ray, and Cortrosyn stimulation test were all negative; urine osmolarity was not diluted, at 582 mOsm/kg; all findings suggesting iatrogenic SIADH. All medications, including clomipramine, were discontinued upon Mrs. A.'s admission to our hospital, and she was given intmvenous saline and furosemide. Serum clomipramine levels were not obtained. Her serum sodium rose slowly on this regimen. It was noted that the patient's cognition, as measured by the Mini-Mental State-Exam (MMSE),5 improved along with her serum sodium. After 6 days on a medical service and then an additional9 days on psychiatry without intravenous sodium or diuretic, the patient'S serum sodium rose to 135 mEqlL. Although her energy was now far improved, with no waxing and waning of lethargy as had been seen on adnlission, she remained depressed. She responded well to a course of electroconvulsive therapy (Een. Three months after her hospitalization, her serum sodium remained normal, at 136 mEq/L. This case demonstrates that iatrogenic SIADH, although uncommon, may result in tenacious symptoms of lethargy and cognitive impairment with persistently low sodium values in very old patients. Mrs. A.'s delirium and low serum sodium delayed new treatment for her depression and prolonged her hospital stay. The long duration of her SIADH may have been related to the long half-life of clomipramine. Other medications given at the same time, such as conjugated estrogens, may have played a role in the persistence of the SIADH, but this interaction has not been well studied. 6 Although tricyclic antidepressants, particularly nortriptyline and desipramine, have a reall,lace in geriatric psychiatry,' it is im.. portant to track serum electrolytes often when prescribing them, particularly in our oldest patients, lest we mistake tIle delirium ofSIADH for an exacerbation ofdepression. References 1. Moses AM, Strecten DHP: Disorders of the neurohypophysis, in Harrison's Principles of Internal Medicine, 13th Edition. Edited by Isselbachcr Kj, Braunwald E, WilsonJD, et aL New York, McGrawHill, 1994, P 1928 2. Anonymous: Antidepressant-induced hyponatraemia. Current Problems in Pharmacovigilance 1994; 20:5-6 3. Garson M: Syndrome of dilutional hyponatraemia secondary to tricyclic antidepressant. Practitioner 1979; 222:411-412 4. Pledger DR, Mathew H: Hyponatracmia and clomipramine therapy. Br J Psychiatry 1989; THEAMEmCANJOURNALOFGEIDATIUCPSYCH~TRY 154:263-264 5. Folstein M~ Folstein SE, McHugh PR: Mini-Mental State: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12:189-198 6. Ciraulo DA, Creeman WL, Shader RI, et al: Antidepressants, in Drug InterJ.ctions in Psychiatry, 2nd Edition. Edited by Ciraulo DA. Baltimore, MD, Williams & \Villdns, 1995, pp 42-43 7. Davidson J: Pharmacological treatment, in Textbook of Geriatric Psychiatry, 2nd Edition. Edited by Busse ~ Blazer DG. Washington, DC, AmeriC.ln Psychiatric Press, 1996, pp 364-365 269