INTRODUCTION:

Depression is kind of psychiatrically ill health. Depression refers to the experience of worry, restlessness, nervousness, tension, fearfulness, apprehensiveness, panic, and agitation.¹Depression is common in the elderly and is a major public health problem. The WHO (2005) also emphasizes that depression, which is the fourth most common illness, can lead to physical, emotional, social and economic problems.² There are several types of depression. A person with major depression experiences symptoms of depression that last for more than two weeks. A person with dysthymia experiences episodes of depression that alternate with periods of feeling normal. A person with bipolar disorder, or manic-depressive illness, experiences recurrent episodes of depression and extreme elation (mania).³ Neurotic depression is a form of depression in which the moods of affected persons depend upon the surrounding environment, such as the time of day - for example, people with this condition may feel extremely depressed during evenings. However, the overall severity of depression is not extreme, and the afflicted persons generally suffer from mild to moderate depression.⁴ Hyponatremia, defined by a serum sodium concentration less than 136 mEq/L, specifies an excess of water relative to sodium in the extracellular fluid compartment.^5,6 Excessive water drinking by psychotic patients can result in water intoxication and hyponatremia, which have been associated with headache, seizures, stupor, coma and death.⁷Hypernatremia is almost always due to a deficiency of water intake, as a result of either a thirst defect or inaccessibility of water.^8,9Hyponatremia is a widely recognized complication of several central nervous system (CNS) disorders.¹⁰ Abnormalites of water and electrolyte metabolism in depressive illness have been reported many times. The subject has been recently review who considers that an increase in intracellular sodium and a low intracellular potassium content are features of the depressed state, the sodium abnormality being reversible.¹¹Several populations are at increased risk of developing hyponatremia, including intensive care unit, postoperative, psychiatric, elderly and nursing home patients.^12-16 Water intoxication with consequent hyponatraemia occurs more frequently in patients with chronic psychiatric illness.¹⁷ Hyponatremia and bipolar disorder are both common and important conditions, but rarely are considered to have common features. Hyponatremia is widely recognized to cause psychiatric and neurological symptoms, especially in patients taking psychotropic medications or suffering from psychotropic polydipsia.¹⁸Changes in serum sodium concentration also have been noted in psychiatric illness. Because sodium is required for the uptake and storage of norepinephrine, it has been hypothesized that altered electrolyte balance may be involved in the aetiology of affective disorders.¹⁹

EPIDEMIOLOGY:

Psychiatric disorders in overall are related with a advanced risk of hyponatremia. The increased risk is primarily attributable to the elevated frequency of primary polydipsia and the prescribing of medications which impair water excretion.^20-26Carbamazepine, thiazide diuretics and antidepressants are the most commonly identified medications. Many psychotropic medications induce transient nausea and orthostatic hypotension, but these are not routinely implicated in hyponatremia in this population.²⁷Among hospitalized patients, the prevalence of hyponatremia ranges between 2.5% and 4.0%,^28,29but it can vary according to the level of care and to whether comorbidity is evident.³⁰Psychiatric disorders are among the clinical conditions associated with an increased risk of hyponatremia. It has been reported a history of hyponatremia in 11% of 61 patients admitted to a long-term care unit at a state psychiatric hospital and in 13% of a subgroup of 32 patients with schizophrenia.³¹Polydipsia has also been associated with affective disorders, organic brain syndrome, anorexia nervosa and personality disorders. Polydipsia can occur in patients without identifiable medical or psychiatric illness.³²

Clinical Features of Hyponatremia Mimicking Psychiatric Illness:

Hyonatremia represents an abnormal ratio of total body sodium to water and is commonly defined as a plasma sodium concentration less than 135mEq/L. Signs and symptoms of Hyponatremia generally do not appear until the serum sodium concentration falls below 130mmol/L. Once the serum sodium falls below 125mmol/L, neuropsychiatric symptoms predominate.^33-35

The clinical manifestations of hyponatremia is largely due to osmotic swelling of brain cells, resulting in neurologic and systemic symptoms.³⁶

· Lethargy

· Restlessness

· Disorientation

· Headaches

· Behavioral changes

· Muscular weakness

· Confusion

· Irritability

· Drowsiness

· Seizures

· Irritability

· Psychotic

· Manic behaviour

Pathophysiology of Hyponatremia in Psychiatric Patients:

Depression is known to influence adults with end-stage renal disease (ESRD) and ascribed to psychosocial and biologic changes that compliment with dialysis. Recent examination has demonstrated that patients with Chronic Kidney Disease (CKD) who are not receiving dialysis have rates of depression up to three times higher than those in the local community. As a rule, depressed patients are at higher risk for suicide and resistance with treatment. They additionally have higher morbidity and mortality caused by renal disease.³⁷ Depression predicts subsequent rapid decline in kidney function, in new onset clinically severe kidney disease (or end-stage renal disease), and hospitalizations that are complicated by acute kidney injury. Substance abuse, alcoholism and suicidal tendency are common in depressive illness. Moreover, they are likely to be non- complaint with regular dialysis, fluid replacement etc.³⁸

The normal kidney has a maximum excretory capacity of 15 to 20L/d and accommodates the ingestion of this amount of free water by producing a physiologic hypotonic diuresis.^39,40 Hyponatremia typically develops in the context of an underlying disturbance of free water elimination, usually as a result of arginine vasopressin (AVP) release or renal failure, also known as antidiuretic hormone, is a peptide hormone produced by the hypothalamus and elated via axons to the posterior pituitary, from which it is released. AVP is primarily responsible for regulating osmotic homeostasis of body fluids, but it also plays a minor role in volume homeostasis, acting mostly through vasopressin type 1A (V_1A) and type 2 (V₂) receptors.^41-43

In one study, for example, patients with polydipsia and hyponatremia at a state psychiatric facility demonstrated impaired maximal urinary dilution and free-water clearance in response to water loading.⁴⁴This abnormality in renal water excretion may be explained by the enhanced sensitivity to low concentrations of AVP.⁴⁵ Several groups have shown that the impaired water excretion in PIP (psychosis, intermittent hyponatremia, polydipsia”) patients is attributable to reset osmostat. In addition, these patients exhibit enhanced renal sensitivity to low levels of AVP. The resetting varies over time appearing to normalize with habituation to the research setting and to worsen during psychotic exacerbations Several investigators initially attributed the variation in the AVP set point to acute stress; however, stress does not increase AVP unless recognized AVP stimuli are induced. The discovery that the anterior hippocampus normally restrains AVP and stress hormone responses to psychological stress and that this hippocampal segment is smaller in PIP patients led to the hypothesis that hippocampal pathology might induce an enhanced AVP response to stress in (PIP) patients. One demonstrated that both AVP and stress hormone responses to a psychological, but not a physical (postural), stimulus were improved in PIP patients relative to healthy controls and non-polydipsic schizophrenics. The AVP response to the psychological stressor was predicted by concurrent plasma osmolality and thus consistent with lowering of the AVP set point. A second study showed that hippocampal mediated negative feedback, which contributes to breaking the stress response, was nearly absent in PIP patients. A third study showed these neuroendocrine findings were proportional to deformations on the surface of the hippocampus overlying the segment which projects to the anterior hypothalamus and normally restrains neuroendocrine release. Together these findings support the conclusion that hippocampal pathology in PIP patients produces symptomatic hyponatremia and water drunkenness by disrupting the restraint of neuroendocrine responses to mental stress.²⁷

The hippocampal findings summarized overhead are also proportional to deformations on the amygdala and anterior hypothalamus ⁴⁶, two structures, like the hippocampus, that modulate both neuroendocrine activity to stress and are implicated in the pathophysiology of schizophrenia. In particular, the same hippocampal area that confines these neuroendocrine responses also confines dopamine release in the ventral striatum, which many believe underlies acute psychosis and behavioural response to stress.⁴⁷ Integrity of the anterior lateral hippocampus also appears necessary for coping efforts to buffer the impact of stress.⁴⁸ Together these findings support the hypothesis that the neuroendocrine dysfunction is part of a general augmented vulnerability to psychological stress in these patients, thus possibly linking the impaired water excretion to the underlying mental disorder.²⁶

Classification of Hyponatremia⁴⁹

· Hypertonic hyponatremia - Hyponatremia with plasma osmolality exceeding 295mOsm/kg (ie, hypertonic or hyperosmolar hyponatremia) suggests factitious hyponatremia secondary to hyper-glycemia or administration of other osmotically active substances such as mannitol.

· Isotonic hyponatremia- Hyponatremia with normal plasma osmolality of 280 to 295mOsm/kg (ie, isotonic or isoosmolar hyponatremia) suggests pseudohyponatremia, a laboratory artefact seen in hyper-proteinemia and hyperlipidemia.

· Hypotonic hyponatremia- Hyponatremia with plasma osmolality less than Hyponatremia with plasma osmolality less than 280mOsm/kg (i.e, hypotonic or hypoosmolar hyponatremia) represents “true” hyponatremia, and assessment of volume status is required to further narrow the differential of underlying causes and direct therapy. Hypotonic Hyponatremia further classified into three following types:

· Hypervolemic hypotonic hyponatremia- Hypervolemic hypotonic hyponatremia results from an increase in total body water and can be further differentiated based on urine sodium concentration. Hypervolemic patients with a urine sodium level exceeding 20Eq/L or fractional excretion of sodium (FENa) exceeding 1% typically have advanced renal failure.

· Euvolemic hypotonic hyponatremia-Euvolemic hypotonic hyponatremia is associated with a group of clinical syndromes that may be further differentiated based on urine osmolality, reflecting more, less, or variably dilute urine. Euvolemia with urine osmolality less than 100mOsm/kg suggests conditions such as psychogenic polydipsia and low-solute potomania.

· Hypovolemic hypotonic hyponatremia-Hypovolemic hypotonic hyponatremia may result from renal or extrarenal losses, and the underlying cause of the losses may be differentiated based on urine sodium concentration

Effect of Hyponatremia on Brain:

Underneath physiological conditions, brain osmolality is in symmetry with extracellular fluid osmolality. When hyponatremia occurs, the resulting reduction in plasma osmolality (with the exception of the rare cases of non-hypoosmotic hyponatremia) causes water movement into the brain in response to the osmotic gradient, thus causing cerebral edema. The cells most involved in swelling are the astrocytes, a kind of glial cells that are a constituent of the blood-brain barrier and have a important role in upholding the fluid and electrolyte concentration of the extracellular space in the brain. Glial cells selectively swell in presence of hyposmolar stress with sparing of neurons, suggestive of the presence of specific water channels contained in astrocytes to protect neurons from the water entrance^50. Glial cells do not act as perfect osmometers. Therefore, when the brain is exposed to a hypotonic environment there is initial swelling. The glial cell then rapidly ejects solutes and water in order to return cell capacity. This response is an energy-dependent phenomenon and needs the Na-K-ATPase system. The enzyme Na-K-ATPase is ubiquitous and plays an vital role in cellular ion homeostasis. In the brain this enzyme is very important in the response of the cell to volume stress in response to hypotonic insult. Most brain cell volume regulation occurs at the expense of the astrocytes, thereby preserving the nerve cell volume. Here are general adaptive mechanisms that are utilized by cells to adapt to an increase in cell volume. Though, the astrocyte responds to cellular swelling differently from many other cells as to the basic mechanisms of the response. The glial cell utilizes ATP-dependent mechanisms at this level of reduced osmolality and this requires the Na-K-ATPase system, which is of primary importance for the extrusion of ions from the glial cell. Brain cells may be reacting not only to changes in cell volume caused by swelling but also to variations in cellular concentration of cytosolic macromolecules. Cellular swelling activates potassium and anion channels, allowing passage of Cl and bicarbonate, but also amino acids. Cell swelling activates the Na/Ca2 exchanger along with Ca2- ATPase, all of which lead to loss of cellular Na. Activation of the Na-K-ATPase system leads to replacement of intracellular Na with K. Cell swelling inhibits glycolysis and stimulates flux through the pentose phosphate pathway. This be likely to enhance the availability of NADPH, which tends to defend the cell against oxidative stress.⁵¹Brain electrolyte content remains relatively constant after these initial losses, and yet the water content of the brain continues to decrease. The progressive decrease in brain water content over time is explained by loss of organic osmolytes, which we once called idiogenic osmoles. Organic osmolytes are intracellular, osmotically active solutes that normally contribute substantially to the osmolality of cell water and that do not adversely affect cell functions when their concentrations change. Organic osmolyte losses from brain cells are comparable in magnitude to cell potassium losses, and there is a strong association between the serum sodium concentration and brain organic osmolyte content. Adaptation to severe hyponatremia is critically reliant on the loss of organic osmolytes from brain cells.⁵²

Antidepressants and Hyponatremia Correlation:

As a class of drugs, antidepressants are used primarily in the management of depressive and anxiety disorders. The drugs used in the management of depression include tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitor (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors and atypical antidepressants that primarily effect on the serotonergic or the noradrenergic neurotransmitter system.⁵³

The association between antidepressants and hyponatremia has been studied extensively in recent years. Some studies have examined electronic health records in Britain, Denmark, Canada, and Sweden through surveying cohort or case-control designs, whereas others have analyzed adverse event reports through drug surveillance or disproportionality methods. Despite these efforts, a agreement for this relationship has not been achieved because of conflicting evidence. For example, some studies have identified a lesser risk of hyponatremia for noradrenergic and specific serotonergic antidepressants (NaSSAs; e.g., mirtazapine), whereas a recent study using the world’s largest spontaneous reporting database found the uppermost reporting risk of hyponatremia for mirtazapine. Mirtazapine (Remeron) is tetracyclic antidepressant (TeCA) chemical classes which is used primarily as an antidepressant. Mirtazapine is a potent antagonist at the following receptors: H1, 5-HT2A, 5-HT2C, 5-HT3, α2-adrenergic. Despite its classification as a NaSSA based on its relatively weak actions at the α2-adrenergic receptor, mirtazapine's antidepressant properties are more likely to actually be mediated primarily by its far stronger blockade of various serotonin receptors, notably the 5-HT2C receptor.⁵⁴Heterogeneity within the same class of antidepressants is also controversial; one population-based cohort study with the largest sample size identified the lowest risk of hyponatremia with escitalopram among SSRIs, whereas other studies found the highest risk of hyponatremia with escitalopram.⁵⁵

Antipsychotic Induced Hyponatremia:

· Fluid restriction with careful monitoring of serum sodium, particularly diurnal variation.

· There is no sign that either reducing or increasing the dose of an antipsychotic results in improvements in serum sodium in water‐intoxicated patients.

· Consider treatment with clozapine which is shown to increase plasma osmolality into the normal range and increase urine osmolality in case of water intoxication.^56,57

· Recently introduced drugs such as tolvaptan, a so‐called vaptan (non‐peptide arginine‐vasopression antagonist – also known as aquaretics because they induce a highly hypotonic diuresis), and show promise in the treatment of hyponatremia of varying etiology, including that caused by drug‐related SIADH.^58,59,60Tolvaptan, is a selective vasopressin V2 receptor antagonist which is available for the treatment of clinically significant hypervolemic and euvolemic hyponatremia was first approved by FDA in May 22, 2009.⁶¹

The Role of Antipsychotics In Hyponatremia²⁷

Antipsychotics also called as neuroleptics are drugs used to treat patients with psychotic disorders such as schizophrenia. These drugs generally tend to decrease the symptoms of psychosis such as hallucinations, delusions and extreme personality disorganization. Almost all antipsychotics generally act by specifically binding to dopamine D2 receptor thereby inhibiting neuronal dopamine release. Besides their actions in the CNS, antipsychotics also have effects in the peripheral sites which contribute to their adverse effects.⁶²

The role of antipsychotic medication in hyponatremia remains controversial. There are undoubted case reports showing rapid reversal of hyponatremia when antipsychotic medication is discontinued, and reappearance with rechallenge. However, this must be balanced with evidence that impaired water excretion predates antipsychotic medications or antipsychotics do not generally increase AVP levels and indeed normalize elevated levels in some with acute psychosis or dose reduction does not improve hyponatremia or lower, not higher, doses are more likely to be associated with hyponatremia. While antipsychotics may modestly improve renal sensitivity to AVP in a dose-related manner, this effect does not appear to contribute to the hyponatremia. These data are consistent with the view that antipsychotic medication does not contribute to the reduced water excretion in most psychotic patients and is more likely to ameliorate hyponatremia in the typical PIP patient. The mechanism of antipsychotic-induced hyponatremia is unknown but rarely involves recognized stimuli (nausea, hypotension). Like other drug-induced cases, antipsychotic-induced hyponatremia is more stable than that seen in PIP patients and is attributable to severe impairments in water excretion that can usually be confirmed with a concurrent urine and plasma osmolality samples. Furthermore, antipsychotic-induced hyponatremia is often confused by other clinical issues like neuroleptic malignant syndrome, rhabdomyolysis, or lung cancer.

DIAGNOSIS:

· Clinical manifestations:

The clinical manifestations of hyponatremia are largely due to osmotic swelling of brain cells, resulting in neurologic and systemic symptoms.^34,63,64With chronic conditions (eg, CHF, hepatic cirrhosis), patients may be asymptomatic because of cellular adaptation via shifting of solutes and organic osmolytes to maintain osmolar gradients and protect from cerebral edema. With more acute manifestations (eg, postoperative, drug-induced), there is a wide range of nonspecific symptoms. Early symptoms are often subtle, such as anorexia, cramping, nausea, vomiting, headache, irritability, disorientation, confusion, weakness, and lethargy, whereas later symptoms can be more profound, such as severe mental status changes, seizure, coma, and respiratory arrest, possibly ending in death.^34,65 When neurologic appearances of hyponatremia are profound, they are sometimes mentioned to collectively as hyponatremic encephalopathy.⁴⁷ Patients with chronic hyponatremia may present with impaired cognition, characterized by deficits in attention, learning, memory, and executive function, which are common to many psychiatric disorders. In addition, anxiety and depression with impaired cognitive performance may be associated with hyponatremia caused by the adverse effects of many psychotropic drugs, including some antipsychotics, hypnotics, and anxiolytics. Antipsychotics may also lower the seizure threshold, thereby increasing the risk of seizure during concurrent hyponatremia.⁴⁴

Treatment of Hyponatremia in Psychiatric Patients:

Ideal treatment in a given case depends primarily on clinical assessment of neurologic symptoms. On the acute end of the clinical spectrum, life-threatening hyponatremic encephalopathy indicates the need for developing treatment with hypertonic solutions, such as 3% saline, to reverse cerebral edema. In contrast, chronic hyponatremia is optimally managed with fluid restriction and removal of any underlying cause, such as drug-induced SIADH. Gradual correction of hyponatremia minimizes the risk of osmotic demyelination as a delayed complication of overly rapid correction of serum Na⁺. Enduring brain damage or death may result from inadequate management or overaggressive correction in acute and chronic cases, respectively.⁴³

1. Acute-onset hyponatremia: Patients with acute-onset hyponatremia may require immediate treatment with hypertonic solutions to reverse cerebral edema, thereby reducing the risk of permanent neurologic injury. Administration of normal (0.9%) saline is contraindicated in hypotonic encephalopathy due to SIADH, as this amount may paradoxically increase cerebral edema by enhancing volume overload.

2. Chronic hyponatremia: Treatment with antipsychotic agents, such as clozapine, may improve polydipsia and hyponatremia in psychiatric patients, as demonstrated in both anecdotal reports and prospective studies. In one report of 10 male psychiatric inpatients with treatment-resistant schizophrenia and hyponatremia, clozapine, when relieved for a traditional neuroleptic, increased serum osmolality an average 15.2 mOsm/kg. A concomitant rise in morning urine osmolality in these patients suggested decreased fluid intake. In a study of 11 hyponatremic patients with treatment resistant schizophrenia or schizoaffective disorder, clozapine increased serum Na⁺ in both the early morning and late afternoon, and decreased the severity of polydipsia. In all of these patients, polydipsia and hyponatremia were alleviated before full remission of psychotic symptoms. Although the mechanism by which clozapine may improve sodium and water balance is not yet known, an effect on renal dopamine D₁receptors has been postulated. The atypical antipsychotic olanzapine was reported to be an ineffective treatment for polydipsia in a double-blind crossover study.⁴³

It has been reported that some severely depressed patients exhibit continued adrenocortical activity which does not respond to normal suppressant doses of exogenous steroids. The mechanism responsible for this effect seems to be extreme release of adrenocorticotrophic hormone (ACTH) from the anterior pituitary, which is under hypothalamic control. Both ACTH and glucocorticoids have been shown to increase intracellular sodium levels in rat brain. Such an increase has been postulated in depressive illness. One might expect this to be reflected in a low Na transfer rate, since the sodium appearing at one hour in the lumber CSF does not come from ventricular fluid. It comes by diffusion from the cord parenchyma and from the vessels of the pia mater.^8,66

A number of hypotheses about the etiology of mood disorders have been clarified by several authors. The NdK-ATP_ase hypothesis for manic depressive illness postulates that a decrease in the NdK-ATP_ase activity of cells in the CNS may be responsible for the mood changes seen in this condition. This model declares that reduced NdK-ATPase activity results in an increased intracellular sodium concentration. This change modifies the transmembrane sodium gradient reducing the membrane potential of the neuron. This renders the neuron more prone to depolarization and thus “hyperexcitable.” This hyper-excitable state results in increased neuronal activity and “mania”. Lithium, an effective treatment for mood disorders, has been shown to increase the activity of the NaK-ATPase.⁶⁷

While psychiatric symptoms attributable to hyponatremia are relatively common, these are typically seen in patients who develop hyponatremia secondary to psychotropic medications or psychogenic polydipsia. Psychiatric disorders due primarily to hyponatremia are rare and poorly described, but our patient represents such a case. The psychiatric manifestations of hyponatremia are widely noted, but in vague terms. Many references include statements such as ‘at a sodium of 115-125 mmol/L agitation, confusion, hallucinations and other neurological symptoms may occur’. Catatonia has been linked with hyponatremia, but primarily in the context of psychogenic polydipsia. There was no finding of a significant association between the severity of catatonic symptoms and serum sodium levels. It has been demonstrateed that specific psychiatric syndromes may be mimicked by hyponatremia at a variety of concentrations, hyponatremia-induced mood disturbance may be more common than widely appreciated.^15,68

The popular of patients with hyponatraemia will respond to cessation of psychotropic drugs and/or one of the above therapies. If long-term fluid limit proves to be intolerable, and the offending drug cannot be withdrawn, demeclocycline, a drug that inhibits ADH at the kidneys, may be used to treat (SIADH). The usual dose is 600-1200 mg daily in divided doses. Demeclocycline may cause photosensitivity reactions. Some patients seem especially prone to psychotropic-induced hyponatraemia. However, prophylactic use of demeclocycline in polydipsic patients has not proved successful.⁶⁹Other prophylactic treatments including naloxone, captopril, propranolol, phenytoin and electrolyte containing drinks have also proved unsuccessful.⁷⁰ Once psychotropic-induced hyponatraemia has occurred, future treatment is made difficult.⁷¹

Recommended Management (Focusing on Psychiatric Aspects).⁷²

· Serum sodium should be determined (at baseline and 2 and 4 weeks and then 3‐monthly for those at high risk of drug‐induced hyponatraemia.

· In most instances, improvement of the underlying electrolyte imbalance will ease the psychiatric symptoms.

· Consider withdrawing other drugs associated with hyponatraemia (risk increases exponentially when antidepressants are combined with diuretics, etc.). The antidepressant should be discontinued immediately If serum sodium is <125 mmol/L.Note risk of discontinuation symptoms which may complicate the clinical picture.

· Agomelatine is effective in older patients, is well tolerated and has not been linked to hyponatraemia

CONFLICT OF INTEREST:

The authors have no conflicts of interest regarding this investigation.

REFERENCES:

1. Makwana Gopal, Jain Sachin Kumar, Vengrelekar Sudha. Evaluation of antidepressant activity of Polyherbal methanolic extract of leaves of Zingiber officinale, Azadirachta indica, Curcuma longa and Hibiscus rosasinesis. Asian Journal of Pharmaceutical Research. 2023; 13(4): 233-6. doi: 10.52711/2231-5691.2023.00043

2. Sangroyangla, Temjentula, Temjenyangla Imchen, Tsungrosenla Longkumer, Vizayieno, Khumjanbeni Murry. Prevalence of Depression and the associated risk factors among the Elderly. Asian J. Nursing Education and Research. 2019; 9(4): 552-554. doi: 10.5958/2349-2996.2019.00119.8

3. Sudhir Patil, Prakash Nargatti, Tabassum Shikalgar, Nilofar Naikwade. Evaluation of Antidepressant activity of Ficus carica leaves extract in experimental animals. Research J. Pharm. and Tech. 2021; 14(3): 1267-1273. doi: 10.5958/0974-360X.2021.00224.9

4. Sheikh Shahid. A Study of Neurotic Depression Associated with Obesity. Int. J. Ad. Social Sciences. 2017; 5(4): 202-204.

5. Adrogu´e HJ, Madias NE. Hyponatremia. N Engl J Med 2000; 342.

6. Kratz A, Ferraro M, Sluss PM, Lewandrowski KB. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Laboratory reference values. N Engl J Med 2004;351.

7. Chinn TA: Compulsive water drinking. J Nerv Ment Dis 158:78-80, 1974

8. Robertson GL, Aycinena P, Zerbe RL. Neurogenic disorders of osmo\x=req-\ regulation. Am J Med .1982;72.

9. Feig PU. Hypernatremia and hypertonic syndromes. Med Clin North Am. 1981; 68: 271-290.

10. Posner JB, Ertel NH, Kossmann RJ, Scheinberg LC. “Hyponatremia in acute polyneuropathy: four cases with the syndrome of inappropriate secretion of antidiuretic hormone.” Archives of Neurology. 1967 17(5): 530-41.

11. Coppen, A.: The Biochemistry of Affective Disorders. Brit J Psychiat. 1967,113.

12. Miller M, Morley JE, Rubenstein LZ. Hyponatremia in a nursing home population. J Am Geriatr Soc. 1995; 43: 1410–3.

13. Ayus JC, Arieff AI. Postoperative hyponatremia. Ann Intern Med. 1997; 126: 1005–6.

14. Chua M, Hoyle GE, Soiza RL. Prognostic implications of hyponatremia in elderly hospitalized patients. Arch Gerontol Geriatr. 2007; 45: 253–8.

15. Sedlacek M, Schoolwerth AC, Remillard BD. Electrolyte disturbances in the intensive care unit. Semin Dial. 2006; 19: 496–501.

16. Siegel AJ, Baldessarini RJ, Klepser MB, McDonald JC. Primary and druginduced disorders of water homeostasis in psychiatric patients: principles of diagnosis and management. Harv Rev Psychiatry. 1998; 6: 190–200.

17. Raskind M, Barnes RF. Water metabolism in psychiatric disorders. Semin Nephro. 1984; 4: 316-324.

18. McKnight RF, Hampson S. Hyponatremia-induced change in mood mimicking late-onset bipolar disorder. General Hospital Psychiatry. 2011. Jan 1; 33(1): 83-e5.

19. Baer L. Electrolyte metabolism in psychiatric disorders. in Mendel J (ed): Biological Psychiatry. 1973, pp 199-234.

20. Jacob S, Spinler SA. Hyponatremia associated with selective serotonin-reuptake inhibitors in older adults. Ann Pharmacother. 2006; 40(9): 1618–22.

21. Kim CS, Choi JS, Bae EH, Kim SW. Hyponatremia associated with bupropion. Electrolyte Blood Press. 2011; 9(1): 23–6.

22. Kirby D, Harrigan S, Ames D. Hyponatraemia 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(3): 231–7.

23. Letmaier M, Painold A, Holl AK, et al. Hyponatraemia during psychopharmacological treatment: results of a drug surveillance programme. Int J Neuropsychopharmacol. 2011; 15(6): 739–48.

24. Palmer BF, Gates JR, Lader M. Causes and management of hyponatremia. Ann Pharmacother. 2003; 37(11): 1694–702.

25. Siegler EL, Tamres D, Berlin JA, Allen-Taylor L, Strom BL. Risk factors for the development of hyponatremia in psychiatric inpatients. Arch Intern Med. 1995; 155(9): 953–7.

26. Van Amelsvoort T, Bakshi R, Devaux CB, Schwabe S. Hyponatremia associated with carbamazepine and oxcarbazepine therapy: a review. Epilepsia. 1994; 35(1): 181–8.

27. Ittasakul P, Goldman MB. Hyponatremia in psychosis. InHyponatremia: Evaluation and Treatment. 2013 Mar 23 (pp. 159-173). New York, NY: Springer New York.

28. Anderson RJ, Chung H-M, Kluge R, Schrier RW. Hyponatremia: a prospective analysis of its epidemiology and the pathogenetic role of vasopressin. Ann Intern Med 1985;102: 164–8.

29. Tierney WM, Martin DK, Greenlee MC, Zerbe RL, McDonald CJ. The prognosis of hyponatremia at hospital admission. J Gen Intern Med 1986; 1: 380–5.

30. Upadhyay A, Jaber BL, Madias NE. Incidence and prevalence of hyponatremia. Am J Med2006; 119(7A): S30–5.

31. de Leon J. Polydipsia. A study in a long-term psychiatric unit. Eur Arch Psychiatry Clin Neurosci2003; 253: 37–9.

32. Illowsky BP, Kirch DG. Polydipsia and hyponatremia in psychiatric patients. The American Journal of Psychiatry. 1988 Jun 1; 145(6): 675-83.

33. Dundas B, Harris M, Narasimhan M. Psychogenic polydipsia review: Etiology, differential and treatment. Current Psychiatry. 2007; Reports 9: 236-241.

34. Levinsky NG (1994) Fluids and electrolytes. In: Isselbacher K, Braunwald E (eds.), Harrison’s Principles of Internal Medicine. McGraw-Hill, New York.

35. Kumar S, Berl T (1998) Sodium. Lancet 352: 220-228.

36. Arieff AI, Llach F, Massry SG. Neurological manifestations and morbidity of hyponatremia: correlation with brain water and electrolytes. Medicine (Baltimore). 1976; 55: 121-129

37. John Rommel P. Cunanan, Christian R. Navarro, Peter Angelo J. Robles, Danielle Mary B. Sanchez, Gerard Josef H. Tuazon, Gil P. Soriano. Depression and quality of life among Chronic Kidney Disease Patients on Hemodialysis at selected Stand-alone Renal Facilities in Manila: a cross-sectional study. Asian J. Nursing Education and Research. 2019; 9(2): 251-255. doi: 10.5958/2349-2996.2019.00053.3

38. R. Andalammal. Depression in Dialysis patient (A Poor Prognostic Factor and the Mechanism behind it). International Journal of Nursing Education and Research. 2023; 11(2): 161-4. doi: 10.52711/2454-2660.2023.00036

39. Riggs AT, Dysken MW, Kim SW, Opsahl JA. A review of disorders of water homeostasis in psychiatric patients. Psychosomatics. 1991; 32: 133–48.

40. Decaux G, MuschW, Soupart A. Hyponatremia in the intensive care: from diagnosis to treatment. Acta Clin Belg. 2000; 55: 69– 78.

41. Rai A, Whaley-Connell A, McFarlane S, Sowers JR. Hyponatremia, arginine vasopressin dysregulation, and vasopressin receptor antagonism. Am J Nephrol. 2006; 26: 579–89.

42. Multz AS. Vasopressin dysregulation and hyponatremia in hospitalized patients. J Intensive Care Med. 2007; 22: 216–23.

43. Ball SG. Vasopressin and disorders of water balance: the physiology and pathophysiology of vasopressin. Ann Clin Biochem. 2007; 44(5): 417–31.

44. Goldman MB, Luchins DJ, Robertson GL. Mechanisms of altered water metabolism in psychotic patients with polydipsia and hyponatremia. N Engl J Med. 1988; 318: 397–403.

45. Siegel AJ. Hyponatremia in psychiatric patients: update on evaluation and management. Harvard Review of Psychiatry. 2008 Jan 1; 16(1): 13-24.

46. Goldman MB, Wang L, Wachi C, et al. Structural pathology underlying neuroendocrine dysfunction in schizophrenia. Behav Brain Res. 2011; 218(1): 106–13.

47. Lodge DJ, Grace AA. Developmental pathology, dopamine, stress and schizophrenia. Int J Dev Neurosci. 2011; 29(3): 207–13.

48. Rowland LM. Who is resilient to depression? multimodal imaging of the hippocampus in preclinical chronic mild stress model May provide clues. Biol Psychiatry. 2011; 70(5): 406–7.

49. Rudolph EH, Pendergraft III WF, Lerma EV. Common electrolyte disorders: Hyponatremia. Hospital Physician. 2009 Jan; 45: 23-32.

50. Giuliani C, Peri A. Effects of hyponatremia on the brain. Journal of Clinical Medicine. 2014; Oct 28;3(4): 1163-77.

51. Ayus JC, Achinger SG, Arieff A. Brain cell volume regulation in hyponatremia: role of sex, age, vasopressin, and hypoxia. American Journal of Physiology-Renal Physiology. 2008; Sep; 295(3): F619-24.

52. Sterns RH, Silver SM. Brain volume regulation in response to hypo-osmolality and its correction. The American Journal of Medicine. 2006; Jul 1; 119(7): S12-6.

53. Priti Das, Jyotiranjan Nayak, Sarada Prasanna Swain. Adverse Drug Reaction Monitoring of Antidepressant Drugs in a Mental Health Institute in Odisha. Research Journal of Pharmacy and Technology. 2021; 14(12): 6479-3. doi: 10.52711/0974-360X.2021.01120

54. Manan A Patel, Chetan M Patel, Dipen B Patel, IS Anand, CN Patel. A Review on Novel Strategies for Pharmacotherapy of Depression. Research J. Pharmacology and Pharmacodynamics. 2010; 2(2): 153-159.

55. Nagashima T, Hayakawa T, Akimoto H, Minagawa K, Takahashi Y, Asai S. Identifying antidepressants less likely to cause hyponatremia: Triangulation of retrospective cohort, disproportionality, and pharmacodynamic studies. Clinical Pharmacology and Therapeutics. 2022; Jun; 111(6): 1258-67.

56. Canuso CM, Goldman MB. Clozapine restores water balance in schizophrenic patients with polydipsia‐hyponatremia syndrome”. J Neuropsychiatry Clin Neurosci. 1999; 11: 86-90.

57. Canuso CM, Goldman MB. Does minimizing neuroleptic dosage influence hyponatremia? Psychiatry Res. 1996; 63: 227-229.

58. Josiassen RC, Curtis J, Filmyer DM, Audino B, Skuban N, et al. Tolvaptan: A new tool for the effective treatment of hyponatremia in psychotic disorders. Expert Opin Pharmacother. 2010; 11: 637-648.

59. Decaux G, Soupart A, Vassart G. Non-peptide arginine-vasopressin antagonists: The vaptans. Lancet. 2008; 371: 1624-1632.

60. Sharma H, Pompei P. Antidepressant‐induced hyponatraemia in the aged. Avoidance and management strategies. Drugs Aging. 1996; 8: 430-435

61. Anna Paul, Lakshmi R. Tolvaptan in Hyponatremia – A Pharmacologic approach. Research Journal of Pharmacy and Technology. 2021; 14(6):3455-0. doi: 10.52711/0974-360X.2021.00601

62. Menaka K, Sarumathy S, Sivakumar T. Study on the adverse reactions of antipsychotics and therapeutic drug monitoring of olanzapine in psychiatric patients. Research J. Pharm. and Tech. 2016; 9(6):687-690. doi: 10.5958/0974-360X.2016.00128.1

63. Moritz ML, Ayus JC. The pathophysiology and treatment of hyponatraemic encephalopathy: an update. Nephrol Dial Transplant. 2003;18: 2486–91.

64. Sterns RH, Silver S, Kleinschmidt-DeMasters BK, Rojiani AM. Current perspectives in the management of hyponatremia: prevention of CPM. Expert Rev Neurother. 2007; 7: 1791–7.

65. Fraser CL, Arieff AI. Epidemiology, pathophysiology, and management of hyponatremic encephalopathy. Am J Med. 1997; 102: 67–77.

66. Carroll BJ, Steven L, Pope RA, Davies B. Sodium transfer from plasma to CSF in severe depressive illness. Archives of General Psychiatry. 1969; Jul 1; 21(1): 77-81.

67. Baar JM. Organic mood disorder, manic type, associated with hyponatremia: a case report. The International Journal of Psychiatry in Medicine. 1994; Sep; 24(3): 223-8.

68. McDaniel WW, Spiegel DR. Hyponatraemia and abnormal ingestion of water in catatonia. Prim Psychiatry. 2010; 17: 29–33.

69. Alexanderr.C. Karp.B. I., Thompsons. et al. A double blind placebo-controlled trial of demeclocycline treatment of polydipsia-hyponatraemia in chronically psychotic patients. Biological Psychiatry. 1991; 3O: 417-420.

70. Thomas.A. and Verbaljs. J. G. Hyponatraemia and the syndrome of Inappropriate antidiuretic hormone secretion associated with drug therapy in psychiatric patients. CNS Drugs. 1995 4. 357-369.

71. McAskill R, Taylor D. Psychotropics and hyponatraemia. Psychiatric Bulletin. 1997; Jan; 21(1): 33-5.

72. Sivaraman S, Rajajeyakumar M. Psychiatric aspects of hyponatremia–A clinical approach. J Psychol Psychother. 2016; 6(6): 1-2.

Received on 06.03.2024 Revised on 08.10.2024

Accepted on 12.02.2025 Published on 28.02.2025

Available online from March 03, 2025

Asian J. Pharm. Res. 2025; 15(1):43-50.

DOI: 10.52711/2231-5691.2025.00008

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