Home | About IPJ | Editorial board | Ahead of print | Current Issue | Archives | Instructions | Contact us |   Login 
Industrial Psychiatry Journal
Search Articles   
    
Advanced search   
 


 
ORIGINAL ARTICLE
Year : 2021  |  Volume : 30  |  Issue : 1  |  Page : 113-117  Table of Contents     

A study to understand the pattern of hyponatremia in patients using selective serotonin reuptake inhibitors and serotonin dopamine antagonists


1 Department of Psychiatry, 158 Base Hospital, Bagdogra, West Bengal, India
2 Department of Psychiatry, INHS Asvini, Mumbai, Maharashtra, India
3 Department of Preventive Medicine, HQ 17 Mountain Division, Gangtok, Sikkim, India

Date of Submission20-Jul-2020
Date of Acceptance25-Apr-2021
Date of Web Publication17-Jun-2021

Correspondence Address:
Dr. Priyadarshee Patra
INHS Asvini, Colaba, Mumbai - 400 005, Maharashtra
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ipj.ipj_146_20

Rights and Permissions
   Abstract 


Introduction: Hyponatremia can be a common but often overlooked side effects of psychotropics drugs. Most patients with drug-induced hyponatremia are asymptomatic and diagnosis is made incidentally following routine blood tests. Objectives: The aim of the study was to understand the pattern of hyponatremia in patients using selective serotonin reuptake inhibitors (SSRI) and serotonin dopamine antagonists (SDA). Materials and Methods: All inpatients and outpatients who were diagnosed with International Classification of Diseases-10 psychiatric disorders and undergoing treatment with SSRI, SDA, or combination of both for the same, were included in the study after simple random sampling, subject to inclusion and exclusion criteria. Statistical Analysis Used: Categorical variables were observed as numbers and percentages. Continuous variables were evaluated as mean ± standard deviation. A Chi-square test was done to find the association between categorical variables. SPSS (IBM) version 21 was used for data analysis. Results: In 150 patients, we found hyponatremia in 17 patients (11.33%). About 66–75 age group patients had maximum found cases of hyponatremia (66.66%). About 20.31% of females found hyponatremia. Among SSRIs, 16% of individuals had hyponatremia whereas among SDA it was 6%. Patients who were taking both SSRIs and SDA total prevalence of hyponatremia was 12%. Conclusions: Older age groups and females had higher chances of hyponatremia while taking SSRIs and SDAs. Among SSRIs, escitalopram had maximum percentage of hyponatremia, whereas fluvoxamine had minimum. Among SDAs, risperidone had maximum percentage, whereas quetiapine had minimum percentage of hyponatremia. Patients who were taking both fluoxetine + olanzapine or fluoxetine + risperidone had higher percentage of hyponatremia.

Keywords: Hyponatremia, serotonin dopamine antagonist, selective serotonin reuptake inhibitor


How to cite this article:
Tomar LK, Patra P, Nigam A. A study to understand the pattern of hyponatremia in patients using selective serotonin reuptake inhibitors and serotonin dopamine antagonists. Ind Psychiatry J 2021;30:113-7

How to cite this URL:
Tomar LK, Patra P, Nigam A. A study to understand the pattern of hyponatremia in patients using selective serotonin reuptake inhibitors and serotonin dopamine antagonists. Ind Psychiatry J [serial online] 2021 [cited 2021 Aug 1];30:113-7. Available from: https://www.industrialpsychiatry.org/text.asp?2021/30/1/113/318700



Sodium plays a vital role in maintaining cellular homeostasis and total sodium body content is the key determinant of extracellular fluid volume and in most circumstances, effective arterial blood volume.[1] Hyponatremia can cause significant morbidity such as lethargy, headache, confusion, convulsions, coma, and can occasionally cause death.[2] Abnormalities in serum sodium, generally defined as hyponatremia if sodium concentration is <135 mmol/l and as hypernatremia, if sodium concentration is >145 mmol/l, virtually always result from disturbances in water balance, with excess or deficit body water relative to body sodium content.[3] The prevalence of hyponatremia is associated with a wide range of medical conditions and pharmacological treatments. Drug-induced hyponatremia is commonly associated with diuretics, SSRI, antipsychotics, and antiepileptics. Most patients with drug-induced hyponatremia are asymptomatic and diagnosis is made incidentally following routine blood tests. Mild cases may be managed either by stopping the drug or by careful observation if the drug is considered essential.[4] Hyponatremia has been described in association with almost all antidepressants drugs. Some studies such as Kris et al. have shown that users of SSRIs in daily clinical practice have an approximately four times higher risk for developing hyponatremia compared with users of other antidepressant drugs. Elderly patients concomitantly using diuretics fall into the highest risk category.[5] Other risk factors for the development of hyponatremia with SSRIs include older age, female gender, and concomitant use of diuretics, low body weight, and lower baseline serum sodium concentration.[6],[7] The mechanism by which SSRIs cause hyponatremia is thought to be secondary to the development of Syndrome of inappropriate antidiuretic hormone secretion.[8] In most of the cases, this effect appears in the first month. Early detection and evaluation of concomitant risk factors in all patients starting antidepressants are important.[9] The treatment of isovolumic hypotonic hyponatremia associated with SSRI use includes water restriction and mild diuresis with a loop diuretic.[10] More severe cases may be treated with higher doses of loop diuretics and hypertonic saline. Furthermore, rechallenge with the same or another SSRI or substitution of another agent from a different therapeutic class has been successfully attempted. In some cases, hyponatremia recurred.[8]

Antipsychotics are also associated with reporting hyponatremia. Sometimes, antipsychotic-associated hyponatremia is underreported due to concomitant use of other medications associated with hyponatremia.[11] Atypical antipsychotic use compared to nonuse was associated with an increased risk of hospitalization with hyponatremia within 30 days.[11] The incidence of hyponatremia induced by antipsychotics may be much higher than is currently thought. Both the newer atypical antipsychotics and the older drugs have been associated with the development of hyponatremia.[12] A number of studies have suggested a possible association between atypical antipsychotics and hyponatremia.[13] Older antipsychotics too contribute to hyponatremia but owing to their side effect profiles, their use has been declining in routine care.[14] Like other psychotropic medications, it is suspected that atypical antipsychotics can induce hyponatremia by either stimulating antidiuretic hormone release from the brain or enhancing antidiuretic hormone activity in the kidneys.[15]


   Materials and Methods Top


This is an analytical study conducted in the Psychiatry Department of a tertiary level hospital located in Kolkata, West Bengal. The study was carried out over 15 months. It was started in December 2014 and data collection was completed in February 2016. The aim of the study was to understand the pattern of hyponatremia in patients using selective serotonin reuptake inhibitors (SSRI) and serotonin dopamine antagonists (SDA). Informed consent was obtained from the selected 150 patients. The approval of the institutional ethics committee was taken for the study.

Three groups were studied separately:

  1. Patients on SSRI
  2. Patients on SDA
  3. Patients on both SSRI and SDA.


The assessment of serum sodium was done at 0, 7, 21, 60, 120, 180, and 240 days using an Eschweiler Electrolyte Analyser in the laboratory of the hospital.

Sample size

Assuming hyponatremia to be present in 10% of the study subjects as brought out by various studies and margin of error of 5% (95% confidence interval: 15%–25%) we calculated sample size to be 139 however for the ease of the study we included 50 patients in each arm. All inpatients and outpatients fulfilling the inclusion criteria, diagnosed with psychiatric illness and undergoing treatment with SSRI, SDA, or combination of both were included in the study. After simple random sampling using a lottery method, a total of 150 patients were finally included in the study comprising 50 patients from each study group as mentioned below:

  1. Patients on SSRI
  2. Patients on SDA
  3. Patients on both SSRI and SDA.


Inclusion criteria

  1. All diagnosed psychiatric cases as per the International Classification of Diseases-10 diagnostic criteria for research, who were adult and receiving SSRI, SDA, or combination of both
  2. Patients who have participated willingly throughout the study.


Exclusion criteria

  1. Patients unwilling to participate or lost to follow-up during the study period
  2. Patients who were suffering from medical illnesses which might cause hyponatremia
  3. Patients who were on medicines which might cause hyponatremia, other than psychotropic drugs
  4. Patients who discontinued treatment before the completion of the study.


Data analysis

Categorical variables were observed as numbers and percentages. Continuous variables were evaluated as mean ± standard deviation. Chi-square test was applied for categorical variable to study their association. Five percentage error of margin has been taken for this study. Hence, any P < 0.05 has been considered to be statistically significant. IBM SPSS statistics V21.0 (Chicago, IL) was used for data analysis.


   Results Top


In this study, 57.3% were male and 42.7% were female. Majority (30.66%) were in the age group of 36–45 years as shown in [Table 1]. In our study population who were taking SSRI, escitalopram was taken by maximum number of cases (9.3%) as shown in [Table 2]. Among patients who were taking SDA, maximum patients (10.7%) were on risperidone as shown in [Table 3]. The most common combination of SSRI with SDA was fluoxetine with olanzapine or risperidone (8.7%) as shown in [Table 4]. Out of total of 150 patients in this study, 17 patients (11.3%) developed hyponatremia [Table 5]. Sixteen percent of patients on SSRI, 6% on SDA, and 12% on combination (SSRI + SDA) developed hyponatremia as shown in [Table 6]. Thirteen females (20.31%) developed hyponatremia, whereas only 4 males (4.65%) developed hyponatremia as shown in [Table 7]. Majority of the cases (66.66%) of hyponatremia were significantly higher in the age group 66–75 (P = 0.000) [Table 8].
Table 1: Age distribution

Click here to view
Table 2: Frequency of various selective serotonin reuptake inhibitors drugs intake

Click here to view
Table 3: Serotonin dopamine antagonists frequency table

Click here to view
Table 4: Both selective serotonin reuptake inhibitors and serotonin dopamine antagonists intake frequency table

Click here to view
Table 5: Number of cases of hyponatremia

Click here to view
Table 6: Frequency of hyponatremia with selective serotonin reuptake inhibitors, serotonin dopamine antagonists and combination of both

Click here to view
Table 7: Gender and hyponatremia

Click here to view
Table 8: Age and hyponatremia

Click here to view



   Discussion Top


There has been widespread use of psychotropic drugs due to increase in prevalence and incidence of mental illnesses. Treatment with combination of two different classes of drugs and polypharmacy has become a common norm as treatment modalities among clinicians. The use of these psychotropic medicines is variable among all age groups and varied side effects of the treatment have come to light. Side effects often lead to poor drug compliance and failure of treatment. There have been studies mentioning about the hyponatremia due to the use of antidepressants and antipsychotics among psychiatric patients. However, to the present knowledge of authors, there are very few studies which have analyzed the pattern of hyponatremia among psychiatric patients with respect to sex, age, duration of treatment, and combination of different classes of drugs. Furthermore, there is dearth of such studies in the Indian setting. This study clearly brings out the pattern of hyponatremia in target population with relation to gender profile, type of drug used, and age of the patient.

Various psychotropic agents including SSRIs, tricyclic antidepressants, monoamine oxidase inhibitors, and antiepileptic drugs can cause hyponatremia. The most common mechanism is by inducing SIADH.[16] Various antipsychotic drugs, both typical and atypical, have been known to cause SIADH. The mechanism by which antipsychotics cause SIADH is not yet clear. There have been various postulated hypotheses in this regard, including long-term D2 receptor blockade leading to D2 receptor supersensitivity, that results in ADH release.[17],[18] There is also antipsychotic-induced hypotension causing ADH release through baroreceptor reflex, along with serotonin-mediated effects on central 5-hydroxytryptamine (5-HT) 2 and 5-HT1c receptors stimulating ADH secretion.[19],[20]

Most of the older patients have multiple comorbidities and often prescribed multiple drugs results in polypharmacy. Few commonly prescribed drugs have hyponatremia as known adverse effects such as thiazide diuretics, and ACEI. Due to changes in kidney functions as a result of aging, there is decreased excretion of drugs leading to increased incidence of hyponatremia.[21]

The majority of hyponatremia cases in the elderly and most of the cases occurring in psychiatric patients have been attributed to SIADH. Causes of SIADH are (a) CNS diseases such as CVA, head injury, and psychosis (b) lung pathologies such as pneumonia, bronchial asthma, atelectasis, pneumothorax, and respiratory failure (c) malignancies such as lung tumors, especially small cell carcinoma, produce ADH ectopically. (d) Other tumors such as cancers of, the duodenum, pancreas, head, and neck may also produce ADH occasionally (e) Hormone administration such as oxytocin, vasopressin, or desmopressin can cause SIADH by enhancing the activity of vasopressor-2 (V2) vasopressin receptor (f) surgical procedures, such as GI and thoracic surgeries and pituitary surgery can also increase the risk of SIADH (g) Both HIV infection and acquired immune deficiency syndrome are associated with SIADH (h) various drugs such as ciprofloxacin, cyclophosphamide, sodium valproate, oxcarbazepine, vincristine, opiate, and nonsteroidal anti-inflammatory drugs , can cause SIADH.[22]

Incidence of hyponatremia in psychiatry patients on SSRI ranges between 0.5% and 25%.[23] The most common SSRIs, predisposing to hyponatremia, reported are citalopram and escitalopram. Risk of hyponatremia is highest, more commonly seen in women than in men.[24] Our study results are consistent with these researches and bring out the same results. Bourgeois et al., have shown that escitalopram-induced hyponatremia is very commonly reported in clinical practices which are in favor of this study.[25] Our study shows that older age groups are more susceptible to the development of hyponatremia with the use of psychotropic drugs. The above results are similarly reported in lots of previous studies such as a study done by Jacob and Spinler reported incidence of SSRI-associated hyponatremia has been variable, ranging from 0.5% to 32%, and was most often observed in older adults.[4] Studies done by Kirby et al., have also suggested that SSRI use is strongly associated with the presence of hyponatremia in a population of elderly psychiatric patients.[26]


   Conclusions Top


Hyponatremia is a life-threatening medical condition that can occur in patients with mental illness on psychotropic medications during treatment. Condition is usually unrecognized, overlooked, and untreated in psychiatric patients. When these drugs are prescribed then patients should be made aware of adverse side effects and sign and symptoms of this condition. If psychotropic-induced hyponatremia occurs, we should withdraw causative drug along with correction of condition with hypertonic saline and other measures. Our recommendation is that monitoring of serum sodium level should be done at regular intervals to diagnose cases with hyponatremia and prevent this life-threatening condition, especially in high-risk population.

Limitations of the study

  • Psychiatric diagnosis was not featured in this study
  • Dose of medications was not mentioned
  • Multiple samples for a single patient for serum sodium assessment at the fixed time interval led to increase in drop-out cases
  • As the study was conducted in a tertiary care setup and the patients had participated from far-flung areas so drug compliance of outpatients has always been a concern especially with those having poor family support. Therefore, possible irregular drug compliance also posed a challenge and risk of estimation error.


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Mount DB. Fluid and electrolyte disturbances. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J, editors. Harrison's Principles of Internal Medicine. 19th ed. New York, NY: McGraw-Hill; 2015.  Back to cited text no. 1
    
2.
Grann AF, Erichsen R, Nielsen AG, Frøslev T, Thomsen RW. Existing data sources for clinical epidemiology: The clinical laboratory information system (LABKA) research database at Aarhus University, Denmark. Clin Epidemiol 2011;3:133-8.  Back to cited text no. 2
    
3.
Verbalis JG. Chapter 15: Disorders of water balance. In: Taal MW, Chertow GM, Marsden PA, Skorecki K, Yu AS, Brenner BM, editors. Brenner and Rector's the Kidney. 9th ed. Philadelphia, PA: Elsevier Saunders; 2012. p. 540-94.  Back to cited text no. 3
    
4.
Jacob S, Spinler SA. Hyponatremia associated with selective serotonin-reuptake inhibitors in older adults. Ann Pharmacother 2006;40:1618-22.  Back to cited text no. 4
    
5.
Movig KL, Leufkens HG, Lenderink AW, van den Akker VG, Hodiamont PP, Goldschmidt HM, et al. Association between antidepressant drug use and hyponatraemia: A case-control study. Br J Clin Pharmacol 2002;53:363-9.  Back to cited text no. 5
    
6.
Sharma H, Pompei P. Antidepressant-induced hyponatraemia in the aged. Avoidance and management strategies. Drugs Aging 1996;8:430-5.  Back to cited text no. 6
    
7.
Ball CJ, Herzberg J. Hyponatremia and selective serotonin reuptake inhibitors. Int J Geriatr Psychiatry 1994;9:819-22.  Back to cited text no. 7
    
8.
Levinsky NG. Fluids and electrolytes. In: Isselbacher K, Braunwald E, editors. Harrison's Principles of Internal Medicine. New York: McGraw-Hill; 1994. p. 242-53.  Back to cited text no. 8
    
9.
Martinez-Cortes M, Ogando-Portilla N, Pecino-Esquerdo B, Perez-Macia V. Antidepressant induced recurrent hyponatremia: A case report. Actas Esp Psiquiatr 2013;41:361-4.  Back to cited text no. 9
    
10.
Ohsawa H, Kishimoto T, Hirai M, Shimayoshi N, Matsumura K, Oribe H, et al. An epidemiological study on hyponatremia in psychiatric patients in mental hospitals in Nara Prefecture. Jpn J Psychiatry Neurol 1992;46:883-9.  Back to cited text no. 10
    
11.
Mannesse CK, van Puijenbroek EP, Jansen PA, van Marum RJ, Souverein PC, Egberts TC. 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.
Palmer BF, Gates JR, Lader M. Causes and management of hyponatremia. Ann Pharmacother 2003;37:1694-702.  Back to cited text no. 12
    
13.
Whitten JR, Ruehter VL. Risperidone and hyponatremia: A case report. Ann Clin Psychiatry 1997;9:181-3.  Back to cited text no. 13
    
14.
Kahn D, Leung M, Kalivas K, Quanbeck C, Su A. Two patients with recurring syndrome of inappropriate secretion of antidiuretic hormone on multiple atypical antipsychotics. J Clin Psychopharmacol 2009;29:186-9.  Back to cited text no. 14
    
15.
Collins A, Anderson J. SIADH induced by two atypical antipsychotics. Int J Geriatr Psychiatry 2000;15:282-3.  Back to cited text no. 15
    
16.
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. 16
    
17.
de Leon J, Verghese C, Stanilla JK, Lawrence T, Simpson GM. Treatment of polydipsia and hyponatremia in psychiatric patients. Can clozapine be a new option? Neuropsychopharmacology 1995;12:133-8.  Back to cited text no. 17
    
18.
Vieweg WV, Leadbetter RA. Polydipsia–hyponatraemia syndrome: Epidemiology, clinical features and treatment. CNS Drugs 1997;7:121-38.  Back to cited text no. 18
    
19.
Raskind MA, Courtney N, Murburg MM, Backus FI, Bokan JA, Ries RK, et al. Antipsychotic drugs and plasma vasopressin in normals and acute schizophrenic patients. Biol Psychiatry 1987;22:453-62.  Back to cited text no. 19
    
20.
Kohen I, Voelker S, Manu P. Antipsychotic-induced hyponatremia: Case report and literature review. Am J Ther 2008;15:492-4.  Back to cited text no. 20
    
21.
Turnheim K. When drug therapy gets old: Pharmacokinetics and pharmacodynamics in the elderly. Exp Gerontol 2003;38:843-53.  Back to cited text no. 21
    
22.
Pillai BP, Unnikrishnan AG, Pavithran PV. Syndrome of inappropriate antidiuretic hormone secretion: Revisiting a classical endocrine disorder. Indian J Endocrinol Metab 2011;15 Suppl 3:208-15.  Back to cited text no. 22
    
23.
Grover S, Biswas P, Bhatja G, Kulhara P. Escitalopram-associated hyponatremia. Psychiatry Clin Neurosci 2007;61:132-3.  Back to cited text no. 23
    
24.
Nahshoni E, Weizman A, Shefet D, Pik N. A case of hyponatremia associated with escitalopram. J Clin Psychiatry 2004;65:1722.  Back to cited text no. 24
    
25.
Bourgeois JA, Babine SE, Bahadur N. A case of SIADH and hyponatremia associated with citalopram. Psychosomatics 2002;43:241-2.  Back to cited text no. 25
    
26.
Kirby D, Harrigan S, Ames D. Hyponatremia in elderly psychiatric patients treated with Selective Serotonin Reuptake Inhibitors and Venlafaxine: A retrospective controlled study in an inpatient unit. Int J Geriatr Psychiatry 2002;17:231-7.  Back to cited text no. 26
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]



 

Top
  
 
  Search
 
  
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
    Materials and Me...
   Results
   Discussion
   Conclusions
    References
    Article Tables

 Article Access Statistics
    Viewed448    
    Printed1    
    Emailed0    
    PDF Downloaded9    
    Comments [Add]    

Recommend this journal