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Comments on “Hyponatremia-induced change in mood mimicking late-onset bipolar disorder”
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General Hospital Psychiatry 33 (2011) e9 – e10
Letter to the Editor Comments on “Hyponatremia-induced change in mood mimicking late-onset bipolar disorder” To the Editor, The interesting report by Drs. McKnight and Hampson [1] related to the hyponatremia-induced development of a manic episode, and subsequently, a state of confusion that progress to catatonia in an older patient inspired us on a few comments. First, during hyponatremia and a fall of extracellular tonicity, in order to preserve their volume, cells must lose K + ions and anions [2]. Some of organic anions, including glycine, γ-aminobutyric acid, glutamate and aspartate, are also neurotransmitters [3]. Furthermore, changes of intracellular and extracellular ions contents have influence on membrane potentials and the electric activity of cells. It has been reported that mild hyponatremia can be an important cause of cognitive deficits in older patients [4] and that important oscillations in psychological functioning associated with metabolic and osmotic changes exist during water loading in hyponatremic schizophrenia patients [5]. Thus, assumptions that mentioned mechanisms may have influences not just on development of certain psychiatric syndromes but also on changes in cognitive functioning of “asymptomatic” persons with euvolemic hyponatremia are logical. However, these issues are insufficiently investigated. Second, hyponatremia is not just the commonest electrolyte abnormality associated with increased morbidity and mortality of elderly but common in patients with tumors, in psychiatric patients, on intensive care units, after surgery and so on [2,6]. However, it is rather neglected that these groups of patients often have insufficient nutrition and that hyponatremia might be associated with malnutrition or changed diet [2]. The described patient's state of confusion and catatonia developed after sertraline (a selective serotonin reuptake inhibitor, or SSRI) was prescribed and after “she had stopped speaking, eating or drinking.“ SSRIs are sometimes a cause of hyponatremia [7]. Although the precise mechanisms involved in the development of hyponatremia related to the use of SSRIs are poorly understood, it is known that the common side effects of SSRIs are vomiting and nausea [8]. Nausea might be not just an important cause for insufficient taking of food but also is a potent stimulus of vasopressin release [9]. Both factors may contribute to the development 0163-8343/$ – see front matter © 2011 Elsevier Inc. All rights reserved.
of hyponatremia. Accordingly, treatment with SSRIs of the patients with hyponatremia should be questionable practice [7], and the measurements of sodium levels in the patients who have poor food intake and/or nausea while treated with SSRIs probably would be needful. Third, would it be more appropriate to use medications only “as needed,” during few days or during next months as in the described case? Beside the development of hyponatremia, the dysregulation of vasopressin function is also thought to be involved in the pathogenesis of different psychiatric conditions (including mood disorders and schizophrenia) [10]. Hyponatremia in psychiatric patients may cause symptoms (e.g., agitation) that may be indistinguishable from symptoms of genuine psychiatric condition. Thus, sometimes the differentiation between new-onset disorder with concomitant hyponatremia and hyponatremia-induced disorder may be difficult. However, if the condition is thought to be hyponatremia induced, then the primary aim should be normalization of sodium blood levels in parallel with clarifying of an etiology of hyponatremia. This approach should help in the differentiation between new-onset disorder with hyponatremia and hyponatremia-induced disorder, and the decisions on prolonged and specific drug treatment should be done afterward. This was not the case in the described patient. Moreover, the patient also developed “a bipolar depressive episode,” and it is not clear whether that episode was caused by hyponatremia. Fourth, the question is: what to do when an extensive investigation has not detected underlying cause for the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and the patient is continuously hyponatremic, like in this case? As mentioned, the rather neglected cause of hyponatremia might be insufficient diet. It has been hypothesized that deficits of potassium, without hypokalemia or other important laboratory findings may cause hyponatremia in some patients with schizophrenia. The therapeutic effect of foods rich in potassium and sufficient amount of proteins on hyponatremia in few patients with schizophrenia has been described. Regardless this theory, which suggests that hyponatremia may be a kind of adaptation on “intracellular hypokalemia,” acceptable in this case or not, it should be noted that addition of potassium may improve hyponatremia and that it is reasonable to believe that during treatment of hyponatremia, a normalization of contents of cations and anions on both sides of cell membrane is needful. Addition of sodium may help but is doubtfully
e10
Letter to the Editor / General Hospital Psychiatry 33 (2011) e9–e10
suitable for normalization of intracellular contents. Accordingly, the main message of this letter is that clinicians who treat patients without identified cause of hyponatremia should have information about rather neglected cause of hyponatremia — contents in patients' food [2]. Branimir Margetić, M.D. Neuropsychiatric hospital “Dr. Ivan Barbot”, Popovača 44317, Popovača, Croatia E-mail address: [email protected] Branka Aukst-Margetić, M.D., Ph.D. Department of Psychiatry University Hospital Center Zagreb Zagreb, Croatia doi:10.1016/j.genhosppsych.2011.01.014 References [1] McKnight RF, Hampson S. Hyponatremia-induced change in mood mimicking late-onset bipolar disorder. Gen Hosp Psychiatry 2011;33 (83):e5–e7.
[2] Margetić B, Aukst-Margetić B. A different hypothesis on hyponatremia in psychiatric patients: treatment implications and experiences. World J Biol Psychiatry 2009;10:677–81. [3] Pasantes-Morales H, Lezama RA, Ramos-Mandujano G, Tuz KL. Mechanisms of cell volume regulation in hypo-osmolality. Am J Med 2006;119(7 Suppl 1):S4–S11. [4] Reddy P, Mooradian AD. Diagnosis and management of hyponatraemia in hospitalised patients. Int J Clin Pract 2009;63: 1494–508. [5] Torres IJ, Keedy S, Marlow-O'Connor M, Beenken B, Goldman MB. Neuropsychological impairment in patients with schizophrenia and evidence of hyponatremia and polydipsia. Neuropsychology 2009;23:307–14. [6] Thompson CJ. Hyponatraemia: new associations and new treatments. Eur J Endocrinol 2010;162:S1-S3. [7] Strachan J, Shepherd J. Hyponatraemia associated with the use of selective serotonin re-uptake inhibitors. Aust N Z J Psychiatry 1998;32:295–8. [8] Wilson K, Mottram P. A comparison of side effects of selective serotonin reuptake inhibitors and tricyclic antidepressants in older depressed patients: a meta-analysis. Int J Geriatr Psychiatry 2004;19: 754–62. [9] Robertson GL. Regulation of arginine vasopressin in the syndrome of inappropriate antidiuresis. Am J Med 2006;119(7 Suppl 1): S36-S42. [10] Ring RH. The central vasopressinergic system: examining the opportunities for psychiatric drug development. Curr Pharm Des 2005;11: 205–25.
General Hospital Psychiatry 33 (2011) e9 – e10
Letter to the Editor Comments on “Hyponatremia-induced change in mood mimicking late-onset bipolar disorder” To the Editor, The interesting report by Drs. McKnight and Hampson [1] related to the hyponatremia-induced development of a manic episode, and subsequently, a state of confusion that progress to catatonia in an older patient inspired us on a few comments. First, during hyponatremia and a fall of extracellular tonicity, in order to preserve their volume, cells must lose K + ions and anions [2]. Some of organic anions, including glycine, γ-aminobutyric acid, glutamate and aspartate, are also neurotransmitters [3]. Furthermore, changes of intracellular and extracellular ions contents have influence on membrane potentials and the electric activity of cells. It has been reported that mild hyponatremia can be an important cause of cognitive deficits in older patients [4] and that important oscillations in psychological functioning associated with metabolic and osmotic changes exist during water loading in hyponatremic schizophrenia patients [5]. Thus, assumptions that mentioned mechanisms may have influences not just on development of certain psychiatric syndromes but also on changes in cognitive functioning of “asymptomatic” persons with euvolemic hyponatremia are logical. However, these issues are insufficiently investigated. Second, hyponatremia is not just the commonest electrolyte abnormality associated with increased morbidity and mortality of elderly but common in patients with tumors, in psychiatric patients, on intensive care units, after surgery and so on [2,6]. However, it is rather neglected that these groups of patients often have insufficient nutrition and that hyponatremia might be associated with malnutrition or changed diet [2]. The described patient's state of confusion and catatonia developed after sertraline (a selective serotonin reuptake inhibitor, or SSRI) was prescribed and after “she had stopped speaking, eating or drinking.“ SSRIs are sometimes a cause of hyponatremia [7]. Although the precise mechanisms involved in the development of hyponatremia related to the use of SSRIs are poorly understood, it is known that the common side effects of SSRIs are vomiting and nausea [8]. Nausea might be not just an important cause for insufficient taking of food but also is a potent stimulus of vasopressin release [9]. Both factors may contribute to the development 0163-8343/$ – see front matter © 2011 Elsevier Inc. All rights reserved.
of hyponatremia. Accordingly, treatment with SSRIs of the patients with hyponatremia should be questionable practice [7], and the measurements of sodium levels in the patients who have poor food intake and/or nausea while treated with SSRIs probably would be needful. Third, would it be more appropriate to use medications only “as needed,” during few days or during next months as in the described case? Beside the development of hyponatremia, the dysregulation of vasopressin function is also thought to be involved in the pathogenesis of different psychiatric conditions (including mood disorders and schizophrenia) [10]. Hyponatremia in psychiatric patients may cause symptoms (e.g., agitation) that may be indistinguishable from symptoms of genuine psychiatric condition. Thus, sometimes the differentiation between new-onset disorder with concomitant hyponatremia and hyponatremia-induced disorder may be difficult. However, if the condition is thought to be hyponatremia induced, then the primary aim should be normalization of sodium blood levels in parallel with clarifying of an etiology of hyponatremia. This approach should help in the differentiation between new-onset disorder with hyponatremia and hyponatremia-induced disorder, and the decisions on prolonged and specific drug treatment should be done afterward. This was not the case in the described patient. Moreover, the patient also developed “a bipolar depressive episode,” and it is not clear whether that episode was caused by hyponatremia. Fourth, the question is: what to do when an extensive investigation has not detected underlying cause for the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and the patient is continuously hyponatremic, like in this case? As mentioned, the rather neglected cause of hyponatremia might be insufficient diet. It has been hypothesized that deficits of potassium, without hypokalemia or other important laboratory findings may cause hyponatremia in some patients with schizophrenia. The therapeutic effect of foods rich in potassium and sufficient amount of proteins on hyponatremia in few patients with schizophrenia has been described. Regardless this theory, which suggests that hyponatremia may be a kind of adaptation on “intracellular hypokalemia,” acceptable in this case or not, it should be noted that addition of potassium may improve hyponatremia and that it is reasonable to believe that during treatment of hyponatremia, a normalization of contents of cations and anions on both sides of cell membrane is needful. Addition of sodium may help but is doubtfully
e10
Letter to the Editor / General Hospital Psychiatry 33 (2011) e9–e10
suitable for normalization of intracellular contents. Accordingly, the main message of this letter is that clinicians who treat patients without identified cause of hyponatremia should have information about rather neglected cause of hyponatremia — contents in patients' food [2]. Branimir Margetić, M.D. Neuropsychiatric hospital “Dr. Ivan Barbot”, Popovača 44317, Popovača, Croatia E-mail address: [email protected] Branka Aukst-Margetić, M.D., Ph.D. Department of Psychiatry University Hospital Center Zagreb Zagreb, Croatia doi:10.1016/j.genhosppsych.2011.01.014 References [1] McKnight RF, Hampson S. Hyponatremia-induced change in mood mimicking late-onset bipolar disorder. Gen Hosp Psychiatry 2011;33 (83):e5–e7.
[2] Margetić B, Aukst-Margetić B. A different hypothesis on hyponatremia in psychiatric patients: treatment implications and experiences. World J Biol Psychiatry 2009;10:677–81. [3] Pasantes-Morales H, Lezama RA, Ramos-Mandujano G, Tuz KL. Mechanisms of cell volume regulation in hypo-osmolality. Am J Med 2006;119(7 Suppl 1):S4–S11. [4] Reddy P, Mooradian AD. Diagnosis and management of hyponatraemia in hospitalised patients. Int J Clin Pract 2009;63: 1494–508. [5] Torres IJ, Keedy S, Marlow-O'Connor M, Beenken B, Goldman MB. Neuropsychological impairment in patients with schizophrenia and evidence of hyponatremia and polydipsia. Neuropsychology 2009;23:307–14. [6] Thompson CJ. Hyponatraemia: new associations and new treatments. Eur J Endocrinol 2010;162:S1-S3. [7] Strachan J, Shepherd J. Hyponatraemia associated with the use of selective serotonin re-uptake inhibitors. Aust N Z J Psychiatry 1998;32:295–8. [8] Wilson K, Mottram P. A comparison of side effects of selective serotonin reuptake inhibitors and tricyclic antidepressants in older depressed patients: a meta-analysis. Int J Geriatr Psychiatry 2004;19: 754–62. [9] Robertson GL. Regulation of arginine vasopressin in the syndrome of inappropriate antidiuresis. Am J Med 2006;119(7 Suppl 1): S36-S42. [10] Ring RH. The central vasopressinergic system: examining the opportunities for psychiatric drug development. Curr Pharm Des 2005;11: 205–25.