Case Report: SIADH-Induced Hyponatremia Following Sertraline and Quetiapine Use in an Elderly Patient with Dementia: A Case Report

Introduction

Hyponatremia, defined as a serum sodium concentration below 135 mEq/L, represents the most common electrolyte abnormality encountered in clinical settings.¹ It occurs in approximately 15–30% of hospitalized patients¹ and is independently linked to a 55% increase in mortality risk, as well as greater healthcare utilization and costs.^2,3

SSRIs are often prescribed for elderly patients for various conditions, such as mood changes or behavioural disturbances associated with dementia. Sertraline is one of the SSRIs frequently prescribed due to its efficacy, tolerability, and safety profile in elderly patients with comorbidities.⁴ However, side effects and complications are possible. One complication is hyponatremia, which could result in SIADH.⁵ In addition, atypical antipsychotics, such as quetiapine, are also commonly prescribed in the elderly for behavioural disturbance associated with dementia.⁶ There are documented case reports stating that quetiapine use could lead to hyponatremia and SIADH⁷ due to serotonin-mediated effects on central 5-HT2 and 5-HT1c receptors, which stimulate ADH release and reset the osmostat, thereby lowering the threshold for ADH secretion.⁵ To our knowledge, documented case reports involving the combination of both sertraline and quetiapine causing SIADH, especially immediately after the addition of quetiapine, are relatively rare. We present a case illustrating the risk, clinical presentation, and challenges.

Case presentation

Discussion

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) refers to excessive release of antidiuretic hormone (ADH) or increased sensitivity of vasopressin receptors to ADH. Unlike normal ADH secretion, which ceases once fluid or cardiac status is corrected, ADH release in SIADH persists despite adequate hydration. SIADH is estimated to account for about one-third of all hyponatremia cases.¹ Typically, the sodium decline occurs gradually over several days or weeks, resulting in mild or absent symptoms.⁸ In most cases, patients remain asymptomatic and the condition is detected incidentally through laboratory testing.⁹ The onset speed and degree of sodium decline largely determine symptom severity. Gradual reductions are often well tolerated, whereas rapid declines may cause life-threatening cerebral edema.¹⁰

Individuals aged over 60 are at increased risk of developing hyponatremia.¹¹ This heightened vulnerability is multifactorial, likely related to reduced total body mass and distribution volume, which enhance the effects of ADH dysregulation. Additionally, decreased glomerular filtration rate, polypharmacy, and multiple comorbidities contribute to the risk.^11,12 Female patients appear more susceptible to psychotropic-induced SIADH than males.¹³ Other risk factors include low body weight and a prior history of hyponatremia.¹¹ Furthermore, non-psychotropic medications and coexisting medical conditions can precipitate SIADH, compounding the risk when psychotropics are used. Smoking has also been implicated as a potential risk factor in psychiatric patients, as nicotine can stimulate ADH secretion.¹² This case illustrates a multifactorial risk of SIADH in elderly dementia patients receiving psychotropics. SSRIs are a well-established cause; antipsychotics, including quetiapine, have been implicated but less frequently. The delayed worsening after sertraline dose increase suggests a possible dose-dependent risk.

Patients who develop SIADH secondary to psychotropic medications usually present with normal volume status but low serum osmolality (<285 mOsm/kg) and inappropriately concentrated urine (>100 mOsm/kg). Hyponatremia in such cases is often multifactorial, with long-term psychotropic users developing low sodium only when additional risk factors coexist. Drug-induced SIADH should be suspected when hyponatremia emerges within two to four weeks of starting a new psychotropic or after a major dose increase, particularly when other potential causes are excluded.¹¹

Antidepressants rank among the three most widely prescribed therapeutic drug classes in the United States.¹⁴ Among them, selective serotonin reuptake inhibitors (SSRIs) have the strongest association with SIADH, accounting for the majority of reported cases. In a 10-year prospective study, Ramírez et al. identified antidepressants as the second most frequent cause of drug-induced SIADH, after thiazide diuretics.¹⁵ Similarly, De Picker et al. reviewed more than 100 case reports and 21 observational studies, concluding that SSRIs consistently showed higher incidence rates than tricyclic antidepressants.¹⁶ The relationship between hyponatremia and both first- and second-generation antipsychotics remains poorly defined, as most available data stem from case reports rather than systematic studies.¹⁷ Quetiapine is a frequently prescribed second-generation antipsychotic (SGA) originally developed for schizophrenia and approved by the U.S. Food and Drug Administration (FDA) in 1997. Subsequent studies expanded its approved indications to include bipolar mania, bipolar depression, and adjunctive therapy in major depressive disorder.¹⁸ However, several previous studies reported cases of quetiapine-induced SIADH in adult and young patients.^19–21

Conclusion

When starting serotonergic and/or antipsychotic medication in the elderly, regular sodium monitoring and cognitive assessment are essential. Subtle changes in mental status should prompt evaluation for reversible metabolic causes such as hyponatremia to avoid misattribution to dementia progression. This case also highlights the importance of a multidisciplinary approach to reaching a diagnosis and management plan.

Ethics

This article is a case report describing the clinical management of a single patient. As a case report, it does not constitute research on human subjects and formal ethical approval from an institutional review board (IRB) was not required under the applicable institutional and national guidelines. The case was managed in accordance with the ethical standards of King Abdulaziz Medical City, Ministry of the National Guard – Health Affairs, Jeddah, Saudi Arabia, and in compliance with the Declaration of Helsinki. Written informed consent for publication was obtained from the patient’s legal guardian prior to submission, as detailed in the Consent section below.

Consent

Written informed consent for publication of their clinical details and/or clinical images was obtained from the patient’s legal guardian.