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 Table of Contents  
CASE SERIES
Year : 2019  |  Volume : 3  |  Issue : 2  |  Page : 168-170

Hyponatremia misdiagnosed as depression


Department of Psychiatry, Seth GSMC and KEM Hospital, Parel, Mumbai, Maharashtra, India

Date of Submission19-May-2019
Date of Decision17-Jun-2019
Date of Acceptance14-Jul-2019
Date of Web Publication18-Dec-2019

Correspondence Address:
Dr. Neena S Sawant
Department of Psychiatry, Seth GSMC and KEM Hospital, Parel, Mumbai - 400 012, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aip.aip_31_19

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  Abstract 


Serotonin reuptake inhibitors, antiepileptics, and antipsychotics are frequently used drugs by psychiatrists for various psychiatric illness which have hyponatremia as a side effect. The symptoms of hyponatremia include lethargy, weakness, headache, and irritability with neuropsychiatric complications such as seizures and confusion. Symptoms of hyponatremia usually occur when serum sodium concentration falls below 130 mEq/L. We report two cases which presented with depressive symptoms but were found to have persistent low serum sodium levels. The depressive features further improved on sodium correction. Both patients were on drugs which caused hyponatremia, a commonly occurring side effect of many medications which often goes undiagnosed. The cases highlight the importance and need for regular evaluation and monitoring.

Keywords: Antidepressants, antiepileptics, depressive features, hyponatremia


How to cite this article:
Sawant NS, Parkar SR, Rupani K, Bansal H, Singh S. Hyponatremia misdiagnosed as depression. Ann Indian Psychiatry 2019;3:168-70

How to cite this URL:
Sawant NS, Parkar SR, Rupani K, Bansal H, Singh S. Hyponatremia misdiagnosed as depression. Ann Indian Psychiatry [serial online] 2019 [cited 2020 Jul 13];3:168-70. Available from: http://www.anip.co.in/text.asp?2019/3/2/168/273375




  Introduction Top


Hyponatremia is one of the most common electrolyte disturbances in which patients present with psychiatric symptoms but often go unrecognized and undiagnosed. Hyponatremia occurs when plasma sodium concentration reduces below 135 mEq/L, and the signs and symptoms are usually observed when serum sodium concentration falls below 130 mEq/L. These include lethargy, restlessness, headache, irritability, and neuropsychiatric symptoms such as disorientation, confusion, drowsiness, and seizures usually predominate when serum sodium falls below 125 mmol/L.[1],[2]

Psychotropic drugs which can cause hyponatremia are antidepressants like serotonin reuptake inhibitors (SSRIs) (escitalopram, sertraline, fluoxetine, and paroxetine), antiepileptics such as carbamazepine and oxcarbazepine, and antipsychotics such as risperidone, clozapine, amisulpride, aripiprazole, and haloperidol. The other classes of drugs causing hyponatremia include diuretics such as indapamide and thiazides, angiotensin-converting enzyme (ACE) inhibitors such as enalapril and captopril, COX-2 inhibitors like celecoxib, and chemotherapeutic agents such as platins and vinca alkaloids, sulfonylureas, proton-pump inhibitors, aspirin, angiotensin receptor blockers, calcium-channel blockers, and opioids.[3],[4]

As clinicians, it is essential to ascertain hyponatremia as it could cause worsening of the preexisting psychopathology or can lead to the new onset of psychiatric symptoms.

We present a case series of two patients diagnosed with depressive symptoms who improved on treatment of the hyponatremia.


  Case Reports Top


Case 1

A 62-year-old female diagnosed with depressive disorder was admitted in 2018 with complaints of sadness of mood, lack of interest in previous pleasurable activities, irritability, inability to do work, increased fatigability, decreased sleep, and appetite present for 1½ months. The patient had a history of similar episode in 2016 for which she was started on tablet fluoxetine (20 mg) 1 tablet in morning and tablet amitryn (25 mg) at night, which was continued for 2 months with complete improvement in symptoms. The patient was noncompliant and did not follow up with us since then. In 2017, patient was admitted in the medical ward with history of accelerated hypertension and one episode of right-sided focal seizure. She was detected to be hypertensive then for the first time. During her admission in the medical ward, patient had 2 days history of fearfulness, auditory hallucinations, and disturbed sleep for which a psychiatric referral was sought. She was found to be perplexed and had confusional behavior. In view of her underlying medical condition, patient was diagnosed with postictal confusion and was given 25 mg quetiapine (25 mg) at bedtime. All her other routine blood investigations done at that time were normal. She was started on carbamazepine 600 mg in divided doses for her seizure and telmisartan (40 mg) for hypertension by her treating physician. Her magnetic resonance imaging of the brain was suggestive of right parietal lobe gliosis and chronic ischemic changes in white matter, and electroencephalography was suggestive of abnormal discharges in bilateral frontal central leads.

After her discharge, patient did not take a psychiatric rereferral.

The patient was well maintained with the above medications and had a regular follow-up in the medical outpatient department (OPD) till she presented to us with depressive features in 2018 for which we admitted her. She was clinically diagnosed with recurrent depressive disorder, current episode mild without somatic complaints as per the ICD 10 criteria. However, no scale was administered to assess the severity of depression. In her medical files, we found that the patient was shifted to oxcarbazepine 900 mg in divided doses from carbamazepine 600 mg a month before this episode, though the reasons for the change of antiepileptic were not found in the medical files. This time she complained more of tiredness, weakness, and sadness. She found it difficult to do her daily chores. There were no symptoms of confusion or psychosis. We found her serum sodium found to be 125 mEq/L on the day of admission, which over the next 4 days dropped to 116 mEq/L. All her routine blood investigations were otherwise within the normal limits. In view of her low sodium, a nephrology reference was also taken and she was investigated for her serum osmolality and urine osmolality which were within normal limits.

In view of her electrolyte disturbance, antidepressants were not considered, and we just undertook the correction of her hyponatremia. Her sodium fluctuations were corrected over 10–12 days with restricted fluid intake. Dietitian reference was taken for the amount of salt to be considered for correction of hyponatremia as well as her underlying hypertension. Her quetiapine was stopped, and the suspected cause of hyponatremia, i.e., oxcarbazepine was tapered off over 5 days and cross titrated to oral valproate by the neurologist. Telmisartan (40 mg) was continued. As the hyponatremia was being corrected, patient started feeling better and reported a decrease in all the mood symptoms with which she had presented. Surprisingly, all her complaints of weakness, tiredness, and lethargy also vanished. At the end of 2 weeks, she felt energetic and euthymic, and her sleep and appetite had normalized. She was discharged on tablet valproate 600 mg in divided doses and telmisartan 40 mg. Her serum valproate levels were 60 μg/ml at the time of discharge, and she is following up regularly both in psychiatric and medical OPD for 10 months. She is currently not on any psychotropic medications and has not reported any depressive features since then.

Case 2

A 60-year-old male diagnosed with depression by private psychiatrist came with complaints of sadness of mood, lack of interest in previous pleasurable activities, inability to do work, crying spells, increased fatigability, muscle aches and pains, and decreased sleep with onset of symptoms for 6 months and worsening over the past 2 months. The patient was already on treatment from a private psychiatrist on tablet escitalopram 10 mg, sertraline 50 mg, and clomipramine 25 mg for 2 months. As there was no improvement in his symptoms, he had come for a second opinion to our hospital. There was no history suggestive of delusions, hallucinations, behavioral problems, headache, giddiness, confusion, etc. As the patient was not improving with antidepressants, history was re-evaluated and reviewed. All his routine investigations were sent along with the thyroid profile, which were then found to be normal except for serum sodium, which was 130 mEq/L. In view of patient being on SSRIs, we did serial sodium levels over the next 4–5 days which showed fluctuations between 130 and 126 mEq/L. Serum osmolality and urine osmolarity were within the normal limits. Nephrology reference was also taken in view of the persistent hyponatremia, and fluid restriction was advised. He was kept only on oral diazepam (5 mg) for sleep disturbances, and the suspected drugs, namely escitalopram, sertraline, and clomipramine, were all stopped. Correction of sodium fluctuations was done by restricting free fluid intake and increasing salt in diet after which serum sodium level became 138 mEq/L after 2 weeks of admission. As the sodium levels were being corrected, we witnessed a significant improvement in the patient's mood. He felt better and did not give sadness of mood or crying spells. He was monitored and discharged after 3 weeks with improvement in his muscle aches, pain, lack of interest and fatigability, sleep, and appetite, and a regular follow-up once a month was done. He has followed up regularly over the past 8 months and is completely better with normal sodium levels. He does not give any depressive features on his follow-up.


  Discussion Top


Both our cases presented with depressive symptomatology which infact were the symptoms of hyponatremia.[1] One of the patients was diagnosed with a primary depressive disorder with the history of previous episode, and the other patient was treated for depressive disorder without much effect. Both the patients had hyponatremia as a side effect of their medication, and the correction of the hyponatremia resulted in the resolution of the depressive symptoms. Drug-induced hyponatremia is seen commonly and with increasing polypharmacy, the prevalence of hyponatremia is likely to increase. The prevalence of hyponatremia has been found to be from 4.8% to 41.5% on carbamazepine [3] and 23%–73.3% on oxcarbazepine.[4] Ryan et al. found that among those patients who developed hyponatremia on oxcarbazepine, about 2.5%–3% had a severe hyponatremia.[5]

Researchers have suggested that hyponatremia usually develops in the first 6 weeks of treatment with antiepileptics like oxcarbazepine.[5] Some studies have reported that hyponatremia due to oxcarbazepine is dose dependent with degree of decline in serum sodium concentration being significantly negatively correlated with dosage of oxcarbazepine. An increase of 1 mg oxcarbazepine is equivalent to an increase in risk of hyponatremia by 0.2%.[6] Several high risk factors for hyponatremia have been proposed as old age (age >80 years), female gender, history of low baseline sodium concentration, medical conditions such as hypothyroidism, diabetes, and hypertension, and history of being on drugs such as antiepileptics, ACE inhibitors, and calcium antagonists.[1]

Our first case was on oxcarbazepine and telmisartan from the medical OPD where her serum sodium monitoring on follow-up was always within the normal limits; however, recent sodium levels after starting oxcarbazepine were not done. We found low sodium with a serial decrease occurring in the serum sodium concentration which would put the patient at risk for neuropsychiatric manifestations. Hence, her oxcarbazepine was gradually reduced to 150 mg and stopped over 4 days with cross titration of oral valproate (600 mg) in divided doses, in view of the patient's history of seizures. What we found surprising was the improvement in the mental status of the patient with the correction of serum sodium levels. The symptoms of sadness of mood, lack of interest in previous pleasurable activities, and fatigability improved with the correction of the serum sodium levels though the patient had clinical symptoms of a depressive episode.

Our second case was on 2 SSRIs, which caused the hyponatremia. Studies have reported hyponatremia in 3%–5% of patients on escitalopram and 5% on sertraline.[7] Among the SSRIs, paroxetine has a greater preponderance for hyponatremia. Paroxetine causes hyponatremia in approximately 12% of the patients.[8] Both our patients were the elderly and were on drugs, which increased their risk.

The mechanism postulated for neurologic complications associated with hyponatremia is the underlying cerebral edema and increased intracranial pressure, caused by the osmotically driven movement of water from the extracellular compartment into brain cell causing swelling of the brain cell and syndrome of inappropriate antidiuretic hormone secretion (SIADH).[4] The physiology of hyponatremia can be explained by the sodium–potassium pump. One of the most important functions of the sodium–potassium pump is to control the volume of each cell. This pump pumps out three sodium ions outside and two potassium ions inside the cell, thus this represents a net loss of ions out of the cell, which initiates osmosis of water out of the cell as well. In the absence of this pump, there will be osmosis of water into the cell causing swelling of the cell.[9] The proposed mechanism for hyponatremia-induced rhabdomyolysis is the malfunction of the muscle cell membrane sodium-calcium pump that can lead to a rise in intracellular calcium and activation of neural protease and lipase, which are responsible for rhabdomyolysis.[10]

However, both our patients did not have SIADH as they did not have neurological signs such as disorientation, myoclonus, seizures, and confusion, and their urine and serum osmolality were normal.

Both the cases inform us about the prevalence of side effects which often go undiagnosed and untreated. As the symptoms of hyponatremia also mimic those of depression, misdiagnosis, and complications could be seen. It is, therefore, essential that as clinicians we do regular monitoring of our patients with gradual dose titration in patients of high risk so that such side effects can be prevented.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for 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.
Sivaraman S, Rajajeyakumar M. Psychiatric aspects of hyponatremia – A clinical approach. J Psychol Psychother 2016;6:1-2.  Back to cited text no. 1
    
2.
Arieff AI, Llach F, Massry SG. Neurological manifestations and morbidity of hyponatremia: Correlation with brain water and electrolytes. Medicine (Baltimore) 1976;55:121-9.  Back to cited text no. 2
    
3.
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. 3
    
4.
Kim YS, Kim DW, Jung KH, Lee ST, Kang BS, Byun JI, et al. Frequency of and risk factors for oxcarbazepine-induced severe and symptomatic hyponatremia. Seizure 2014;23:208-12.  Back to cited text no. 4
    
5.
Ryan M, Adams AG, Larive LL. Hyponatremia and leukopenia associated with oxcarbazepine following carbamazepine therapy. Am J Health Syst Pharm 2001;58:1637-9.  Back to cited text no. 5
    
6.
Lin CH, Lu CH, Wang FJ, Tsai MH, Chang WN, Tsai NW, et al. Risk factors of oxcarbazepine-induced hyponatremia in patients with epilepsy. Clin Neuropharmacol 2010;33:293-6.  Back to cited text no. 6
    
7.
Lien YH. Antidepressants and hyponatremia. Am J Med 2018;131:7-8.  Back to cited text no. 7
    
8.
Fabian TJ, Amico JA, Kroboth PD, Mulsant BH, Corey SE, Begley AE, et al. Paroxetine-induced hyponatremia in older adults: A 12-week prospective study. Arch Intern Med 2004;164:327-32.  Back to cited text no. 8
    
9.
Guyton C, Hall JE. Membrane potentials and action potentials. Textbook of Medical Physiology. 12th ed. Philadelphia: Elsevier Publications; 2011. p. 55-7.  Back to cited text no. 9
    
10.
Varghese J, Balakrishnan V, Sadasivan S, Nair P, Narayanan VA. Muscle cell membrane damage by very low serum sodium. Pan Afr Med J 2009;3:14.  Back to cited text no. 10
    




 

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