Hyponatraemia and the syndrome of inappropriate antidiuretic hormone secretion with convulsions, coma and pulmonary oedema in a patient using paroxetine

TheNetherlands

JOURNALOF MEDICINE ELSEVIER

Netherlands

Journal

of Medicine

51 (1997)

237-239

Letter to the Editor

Hyponatraemia and the syndrome of inappropriate antidiuretic hormone secretion with convulsions, coma and pulmonary oedema in a patient using paroxetine J.M. van der Klooster a3* , R. Peters a, R.Z. Ashruf a, A.F. Grootendorst a,b a Department of Internal Medicine, St. Clara Ziekenhuis, Olympiaweg 350, 3078 HT Rotterdam, Netherlands b Department of Intensive Care Medicine, St. Clara Ziekenhuis, Olympiaweg 350, 3078 HT Rotterdam, Netherlands Received

20 June 1997; revised

8 September

1. Introduction Hyponatraemia and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) have been associated with many psychotropic drugs including carbamazepine, neuroleptics, tricyclic antidepressants and more recently selective serotonin re-uptake inhibitor (SSRI) antidepressants (fluoxetine, fluvoxamine, sertraline, paroxetine and venlafaxine) [1,2]. SSRIs are generally better tolerated than the traditional tricyclic antidepressants, but are associated with side effects which clinicians may not be aware of [2]. Documented cases of SSRI-induced hyponatraemia and SIADH almost exclusively involve female geriatric patients and demonstrate an onset of symptoms and electrolyte changes predominantly within the first 2 weeks of treatment [3,4]. Since 1992, only nine cases of hyponatraemia due to the use of paroxetine have been reported [5-121. Recently, Meynaar et al. reported two patients with SIADH during treatment with venlafaxine and paroxetine [1:2]. We want to describe an additional

* Corresponding author. Present address: Department of Internal Medicine, Ijsselland Ziekenhuis, P.O. Box 690, 2900 AR Capelle aan den Ijssel; Tel. +31 10 2585000; Fax: +31 10 4586261. 0300-2977/97/$17.00 0 1997 Elsevier PII SO300-2977(97)00075-2

Science

B.V.

All rights

reserved.

1997; accepted

9 September

1997

case of life-threatening paroxetine-induced hyponatraemia complicated by coma, convulsions and pulmonary oedema, and wish to alert internists to these rare, but potentially lethal complications.

2.

Case report

A 5%year-old woman was referred to our hospital because of confusion and lethargy. Her medical history revealed hypertension, hypercholesterolaemia, and several small operations of the breast and urinary bladder. In the past, she had been successfully treated for depressive symptoms with paroxetine for a few months. Three weeks before admission, paroxetine (20 mg daily) was prescribed by her general practitioner for symptoms of anxiety and depression. Her other medication consisted of simvastatin (10 mg daily), carvedilol (25 mg daily), oxazepam and diazepam. Six weeksbefore admission, the laboratory and urinary examinations showed no abnormalities. On admission the patient was disorientated and lethargic. Her blood pressure was 185/100 mmHg, and heart rate regular at 102/min. Physical and neurological examination revealed no abnormalities, in particular no peripheral oedema. On the presumptive diagnosis of a suicide attempt with tranquillizers

she was transferred to the Intensive Care Unit for observation. Toxicological screening of the blood and urine for benzodiazepines showed concentrations within the therapeutic range. However, the serum sodium concentration was 118 mmol/l (normal 135-145 mmol/l>, serum osmolality was 263 mosmol/kg (normal 280-300 mosmol/kg), potassium concentration was 3.1 mmol/l (normal 3.6-5.1 mosmol/kg). Urine osmolality was 45.5 mosmol/kg (normal 200-l 200 mosmol/kg), urine sodium concentration was 106 rmnol/l, urine potassium concentration was 38 mmol/l. Electrocardiography and chest radiography showed no abnormalities. Urea, creatinine, haemoglobin and cholesterol concentrations, liver, thyroid and adrenal function tests were normal. A diagnosis of SIADH due to paroxetine was made. Her condition gradually deteriorated and she became deeply comatose (Glasgow Coma Scale E, M 3V, ). She developed generalized tonic-clonic convulsions, Babinski signs and tachypnoea. Computerised tomography of the brain was normal. Blood gas analysis showed hypoxaemia: ~0, 55 mmHg (normal 80-100 mmHg) and $0, 29 mmHg (normal 35-45 mmHg1. A second chest X-ray showed bilateral pulmonary oedema (Fig. 11, which had de-

Fig. 1. Chest X-my

(taken

4 h after admission)

veloped within 4 h. By supplying oxygen (10 l/min>, the saturation became normal. Her fluid intake was restricted and all drugs were discontinued. With infusion of hypertonic saline and administration of furosemide the serum sodium concentrations gradually normalized within 3 days. The next morning, a chest X-ray showed a considerable reduction of the pulmonary oedema. She made a complete recovery, but developed delusions, for which haloperidol was given. Except for paroxetine, all other drugs were restarted. The serum sodium concentrations remained within the normal range throughout the following days. Rechallenge was thought to be unethical.

3. Discussion Our case illustrates the potentially life-threatening complications of severe hyponatraemia associated with the use of SSRIs. Although plasma ADH concentrations were not measured, the diagnosis of paroxetine-induced SIADH was supported by the serum and urine electrolyte abnormalities, the absence of any other known cause of SIADH and the complete recovery after discontinuation. The features

shows bilateral

pulmonary

oedema

J.M. uan der Klooster

et al. /Netherlands

of SIADH may mimic depressive symptoms, and thus may present as a worsening of depression in a person receiving seemingly adequate antidepressant therapy. There may be a delay of several months before SIADH develops [l-4,8]. Therefore, hyponatraemia and SIADH should be considered in any patient using SSRIs, who experiences a deterioration in his or her clinical condition, regardless of the duration of treatment or age. It has been unclear whether hyponatraemia that develops from treatment with one SSRI will recur if a second is introduced. A patient who develops SIADH with one SSRI might do so when treated with another, and should therefore be carefully monitored [7,8,12]. On the other hand, negative findings after rechallenge have been observed with different SSRIs [ 1,111. There is no clear explanation why our patient only developed symptoms of hyponatraemia following the second exposure to paroxetine. We subscribe to the viewpoint of Meynaar et al. that, if continued antidepressant therapy is indicated, a drug with a different pharmacological profile should be chosen, and that serum sodium levels should be monitored closely. Pulmonary oedema is an unusual complication in a patient with SIADH, since urinary excretion of sodium is gen~erally increased. Our patient developed coma and grand mal seizures due to hyponatraemia. This results from generalized cellular oedema and subsequent compression of the brain by the unyielding cranial vault. Acute pulmonary oedema in association with raised intracranial pressure, seizures and head trauma i.s a well-known, but infrequent, phenomenon. Clinical and experimental studies suggest that both increased pulmonary microvascular pressure and increased permeability may be involved, probably by generalized sympathetic discharge. For unknown reasons, the distribution of neurogenic pulmonary oedema is unpredictable and frequently asymmetric. Characteristically, it develops immediately after an epileptic seizure, or can be delayed for several hours, and disappears within several days following the aevent [13].

Journal

of Medicine

51 (I 997) 237-239

239

Acknowledgements We would like to thank Mr. D. Zoetekouw for preparing the photograph.

References [ll Spigset 0, Hedenmalm K. Hyponatraemia and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) induced by psychotropic drugs. Drug Saf 1995;12:209-225. Dl Van Ermen AMC, Ottervanger JP, Roisin T, Kurz X, Stricker BHCh. Meldingen van vermoedelijke bijwerkingen van selectieve serotonine-beropnameremmers in BelgB en Nederland. Ned Tijdschr Geneesk 1996;140:1817-1820. [31 Pillans PI, Coulter DM. Fluoxetine and hyponatraemia - a potential hazard in the elderly. New Zealand Med J 1994;107:85-86. [41 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. Can Med Assoc J 1996;155:519-527. El Goddard C, Paton C. Hyponatraemia associated with paroxetine [letter]. Br Med J 1992;305:1332. b1 Chua TP, Vong SK. Hyponatraemia associated with paroxetine [letter]. Br Med J 1993;306:143. [71 Ayonrinde OT, Reutens SG, Sanfilippo FM. Paroxetine-induced SIADH [letter]. Med J Aust 1995;163:390. [81 Flint AJ, Crosby J, Genik JL. Recurrent hyponatremia associated with fluoxetine and paroxetine [letter]. Am J Psychiatry 1996;153:134. [9] Christensen 0, Sorensen HA, Almdal TP. Bivirkninger ved behandling med selektive serotoningenoptagelseshaemmere. Hyponotrioemi pa grund af Schwartz-Bartters syndrom. Ugeskr Laeger 1996;158:6920-6922. [lo] Van Campen JP, Voets AJ. SIADH caused by paroxetine [letter]. Ann Pharmacother 1996;30:1499. [ 111 John L, Perreault MM, Tao T, Blew PG. Serotonin syndrome associated with nefazodone and paroxetine. Ann Emerg Med 1997;29:287-289. [12] Meynaar IA, Peeters AJ, Mulder AH, Ottervanger JP. Syndrome of inappropriate ADH secretion attributed to the serotonin re-uptake inhibitors venlafaxine and paroxetine. Neth J Med 1997;50:243-245. [13] Fraser RG, Pa& JAP, Par6 PD, Fraser RS, Genereux GP, editors. Diagnosis of diseases of the chest, 3rd ed. Philadelphia: Saunders, 1990;3:1926-1927.