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 Table of Contents  
CASE REPORT
Year : 2018  |  Volume : 5  |  Issue : 1  |  Page : 75-77

Quetiapine-induced hyponatremia in elderly


Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India

Date of Web Publication27-Jun-2018

Correspondence Address:
Palanimuthu Thangaraju Sivakumar
Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru - 560 029, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jgmh.jgmh_2_18

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  Abstract 


Quetiapine is a second-generation antipsychotic used for the treatment of severe mental illness. Quetiapine has a relatively safer side effect profile with lesser propensity to cause extrapyramidal side effects. Antipsychotics have been rarely reported to cause hyponatremia, especially in the elderly. There is a paucity of literature on the association between quetiapine and hyponatremia. Elderly due to their multiple medical comorbidities and frequent polypharmacy are at higher risk of developing hyponatremia. In this article, we describe a case of elderly gentleman who presented with chronic hyponatremia probably secondary to quetiapine use.

Keywords: Bipolar disorder, elderly, hyponatremia, quetiapine


How to cite this article:
Reddy Mukku SS, Sivakumar PT, Arumugahm SS. Quetiapine-induced hyponatremia in elderly. J Geriatr Ment Health 2018;5:75-7

How to cite this URL:
Reddy Mukku SS, Sivakumar PT, Arumugahm SS. Quetiapine-induced hyponatremia in elderly. J Geriatr Ment Health [serial online] 2018 [cited 2018 Dec 18];5:75-7. Available from: http://www.jgmh.org/text.asp?2018/5/1/75/235364




  Introduction Top


Quetiapine chemically is a dibenzothiazepine derivative included under the category of atypical antipsychotics. Quetiapine is used in the management of severe mental illness such as psychosis and bipolar disorder. Quetiapine has low propensity to cause extrapyramidal side effects due to its lesser affinity and transient binding to dopamine D2 receptor.[1] This property makes quetiapine to be prescribed more often than high-potency antipsychotics. Elderly have higher risk of extrapyramidal side effects and are more likely to have comorbid Parkinson's spectrum diseases.[2] Hence, quetiapine is considered as one of the first choice in geriatric patients. The common adverse effects of quetiapine are sedation, weight gain, postural hypotension, QT interval prolongation, and transient elevation of prolactin.[3]

Hyponatremia is defined as a serum sodium <135 mEq/l.[4] It is the most common electrolyte abnormality seen in clinical practice.[5] The clinical features depend on the onset and severity of hyponatremia. Elderly are at more risk of hyponatremia due to physiological changes, multiple comorbidities, and polypharmacy.[6],[7] There are case reports and case series suggesting an association between antipsychotic use and hyponatremia, especially in the elderly. However, there is very limited literature specifically about quetiapine-induced hyponatremia.[8],[9] In this article, we report about an elderly man who developed hyponatremia, possibly in association with use of quetiapine. We also review the relevant literature on this aspect.


  Case Report Top


A 62-year-old gentleman with bipolar affective disorder was brought to our outpatient department for a follow-up. His wife and son reported that the patient has forgetfulness and stopped going to work. He was admitted for further evaluation of cognitive decline. He was premorbidly well adjusted. He had history of nicotine use in dependence pattern with abstinence since 5 years. He also had hypertension and diabetes mellitus. He had six episodes of mania and one episode of depression in the past. His last episode of hypomania was 3 years before the index admission. He is on treatment with tablet telmisartan 40 mg, tablet amlodipine 5 mg, tablet glimepiride 2 mg, tablet metformin 1500 mg, and tablet quetiapine 200 mg. During the current inpatient care, it was found that, since past 18 months, he has slowness in doing activities, dullness, difficulty in focusing, patchy forgetfulness for recent events, and apathetic behavior. The patient had recurrent episodes of vomiting 6 months ago, and he was found to have hyponatremia on evaluation. He was admitted to a medical setup and correction of sodium was done. During the same time, antihypertensive medication was rationalized and tablet hydrochlorothiazide which he was taking along with telmisartan was stopped in view of hyponatremia. He was started on telmisartan and amlodipine combination for the last 6 months. On physical examination, his pulse rate was 90 bpm, BP was 140/70 mm of Hg, and other system examination was normal, and there were no focal deficits. Mental status examination showed deficits in attention and concentration. His Hindi Mental State Examination score was 22/31 and Addenbrooke's cognitive examination score was 55/100. Details about his blood investigation report are shown in [Table 1], and his serum sodium was 126 mmol/L.
Table 1: Laboratory investigations

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The diagnosis was provisionally considered as cognitive decline secondary to hyponatremia. He was evaluated for the possible causes of hyponatremia and investigated as shown in [Table 1]. The patient was given Sodium bicarbonate PO and water intake was restricted to 1 L/day. Despite this, his sodium levels continued to decrease. At this stage, a physician's opinion was taken and was started on tablet tolvaptan up to 30 mg/day. After 2 days, the serum sodium was 115 mmol/l. The patient was transferred to a medical setup due to a very low sodium level. During the treatment of patient in medical setup, the physician has stopped quetiapine, and this led to near complete improvement of hyponatremia. The serum sodium level came to nearly normal (134 mEq/L) and maintained like that nearly for 4 weeks. After a few weeks, the patient developed behavioral problems in the form of irritability, decreased sleep, and restlessness. He was prescribed tablet quetiapine by another psychiatrist, which again leads to the development of hyponatremia (126 mEq/L). Patients continued to have cognitive deficits, and he was diagnosed to have dementia in addition to hyponatremia.


  Discussion Top


This patient presented with predominant cognitive complaints. On evaluation, he had hyponatremia which did not respond to salt intake, water restriction, and treatment with tolvaptan. His sodium level improved significantly after discontinuing quetiapine. Hyponatremia was persistent in this patient for few months after stopping hydrochlorothiazide. Initially, the treating team did not consider quetiapine as the likely cause for hyponatremia and we also had concern about the risk of relapse with complete discontinuation of antipsychotics. However, due to the persistence of hyponatremia with continued symptomatic treatment and the opinion of physician suggesting quetiapine-induced hyponatremia, we attempted gradual discontinuation of quetiapine. Hyponatremia significantly improved after discontinuing quetiapine. This patient developed hyponatremia again on rechallenge with quetiapine. In this case, applying the Naranjo Adverse Drug Reaction Scale, the score was six, indicating probable drug reaction to quetiapine.[10]

In a systematic review on antipsychotic-induced hyponatremia that included case series, reports, and few observational studies, the mean age of patients was 46 years. The diagnosis was schizophrenia in 70% of the cases, and there was history of polydipsia in 67% of the cases.[8] In a population-based cohort study, elderly patients prescribed with atypical antipsychotics had an increased risk of hospitalization with hyponatremia (relative risk of 1.62) compared to nonusers.[9] In a case–control study based on the WHO global safety database, estimated adjusted odds ratio for antipsychotic induced hyponatremia was 1.58 (95% confidence interval 1.46, 1.70).[11] Among the antipsychotics most reported cases were on risperidone, olanzapine, and clozapine.[11] The common risk factors for hyponatremia in elderly include female gender, low body weight, history of hyponatremia, summer season, antidepressant use, early-onset psychiatric illnesses, longer duration of psychiatric disorder, prolonged admission, presence of comorbid medical conditions, concomitant use of diuretics, and antihypertensive.[12]

The common cause of hyponatremia associated with any psychotropic drug is through the increased secretion of antidiuretic hormone (ADH) and increased responsiveness of kidneys to ADH, commonly known as syndrome of inappropriate secretion of ADH.[13] There is no clear specific mechanism related to quetiapine. The patient also had mild nonobstructive hydronephrosis on the right side. The nonobstructive hydronephrosis develops secondary to fluid excess excretion through urinary tract either due to polydipsia or nephrogenic diabetes insipidus.[14],[15] Polydipsia can result in hyponatremia and hydronephrosis. In this case, the patient has hydronephrosis of mild severity on one side which might be due to polydipsia. The contributing factors for hyponatremia in our patients are elderly age, polydipsia, severe mental illness, antihypertensive medication (hydrochlorothiazide), and psychotropics (quetiapine).

Regarding the literature on quetiapine-induced hyponatremia, there are four cases reported to the best of our knowledge as shown in [Table 2].[16],[17],[18],[19] In two cases, the patients developed hyponatremia on 200–300 mg dose of quetiapine, and it resolved with quetiapine withdrawal.[18],[19]
Table 2: Case reports on quetiapine-induced hyponatremia

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  Conclusion Top


Hyponatremia is a frequently encountered condition in elderly. In many patients, it is contributed by many factors including medication. This case report highlights the hyponatremia probably induced by quetiapine. One should be cautious when using antipsychotics in elderly and should monitor for serum sodium level. Antipsychotics, including quetiapine use, should be considered while evaluating the causes of hyponatremia, especially in elderly.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
DeVane CL, Nemeroff CB. Clinical pharmacokinetics of quetiapine: An atypical antipsychotic. Clin Pharmacokinet 2001;40:509-22.  Back to cited text no. 1
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2.
Caligiuri MR, Jeste DV, Lacro JP. Antipsychotic-induced movement disorders in the elderly: Epidemiology and treatment recommendations. Drugs Aging 2000;17:363-84.  Back to cited text no. 2
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Garver DL. Review of quetiapine side effects. J Clin Psychiatry 2000;61 Suppl 8:31-3.  Back to cited text no. 3
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4.
Verbalis JG, Goldsmith SR, Greenberg A, Korzelius C, Schrier RW, Sterns RH, et al. Diagnosis, evaluation, and treatment of hyponatremia: Expert panel recommendations. Am J Med 2013;126:S1-42.  Back to cited text no. 4
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Sherlock M, Thompson CJ. The syndrome of inappropriate antidiuretic hormone: Current and future management options. Eur J Endocrinol 2010;162 Suppl 1:S13-8.  Back to cited text no. 5
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Soiza RL, Hoyle GE, Chua MP. Electrolyte and salt disturbances in older people: causes, management and implications. Rev Clin Gerontol 2008;18:143-58. Available from: https://www.cambridge.org/core/journals/reviews-in-clinical-gerontology/article/electrolyte-and-salt-disturbances-in-older-people-causes-management-and-implications/0FE087683B6C18AD5E953850BCD6BF7F. [Last. [Last accessed on 2017 Nov 21].  Back to cited text no. 6
    
7.
Soiza RL, Cumming K, Clarke JM, Wood KM, Myint PK. Hyponatremia: Special considerations in older patients. J Clin Med 2014;3:944-58.  Back to cited text no. 7
    
8.
Meulendijks D, Mannesse CK, Jansen PA, van Marum RJ, Egberts TC. Antipsychotic-induced hyponatraemia: A systematic review of the published evidence. Drug Saf 2010;33:101-14.  Back to cited text no. 8
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Gandhi S, McArthur E, Reiss JP, Mamdani MM, Hackam DG, Weir MA, et al. Atypical antipsychotic medications and hyponatremia in older adults: A population-based cohort study. Can J Kidney Health Dis 2016;3:21.  Back to cited text no. 9
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10.
Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. Amethod for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.  Back to cited text no. 10
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11.
Mannesse CK, van Puijenbroek EP, Jansen PA, van Marum RJ, Souverein PC, Egberts TC, et al. Hyponatraemia as an adverse drug reaction of antipsychotic drugs: A case-control study in vigiBase. Drug Saf 2010;33:569-78.  Back to cited text no. 11
    
12.
Sahoo S, Grover S. Hyponatremia and psychotropics. J Geriatr Ment Heal 2016;3:108.  Back to cited text no. 12
    
13.
Liamis G, Milionis H, Elisaf M. A review of drug-induced hyponatremia. Am J Kidney Dis 2008;52:144-53.  Back to cited text no. 13
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14.
Maroz N, Maroz U, Iqbal S, Aiyer R, Kambhampati G, Ejaz AA, et al. Nonobstructive hydronephrosis due to social polydipsia: A case report. J Med Case Rep 2012;6:376.  Back to cited text no. 14
    
15.
Nakada T, Miyauchi T, Sumiya H, Shimazaki J. Nonobstructive urinary tract dilatation in nephrogenic diabetes insipidus. Int Urol Nephrol 1990;22:419-27.  Back to cited text no. 15
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16.
van den Heuvel OA, Bet PM, van Dam EW, Eeckhout AM. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) during treatment with the antipsychotic agents haloperidol and quetiapine. Ned Tijdschr Geneeskd 2006;150:1944-8.  Back to cited text no. 16
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Atalay A, Turhan N, Aki OE. A challenging case of syndrome of inappropriate secretion of antidiuretic hormone in an elderly patient secondary to quetiapine. South Med J 2007;100:832-3.  Back to cited text no. 17
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18.
Kenes MT, Hamblin SE, Tumuluri SS, Guillamondegui OD. Syndrome of inappropriate antidiuretic hormone in a patient receiving high-dose haloperidol and quetiapine therapy. J Neuropsychiatry Clin Neurosci 2016;28:e29-30.  Back to cited text no. 18
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19.
Koufakis T. Quetiapine-induced syndrome of inappropriate secretion of antidiuretic hormone. Case Rep Psychiatry 2016;2016:3. [doi.org/10.1155/2016/4803132].  Back to cited text no. 19
    



 
 
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