Mirtazapine-Induced Severe Hyponatremia in a Young Man Taking Oxcarbazepine

Hyponatremia is a known adverse effect associated with various medications, including antidepressants and antiepileptics.¹ The most common mechanism of drug-induced hyponatremia is syndrome of inappropriate antidiuretic hormone (SIADH) secretion, in which excessive antidiuretic hormone causes hyponatremia by increasing renal water absorption.² This most often occurs in older patients, with a mean age of 67.9±16.9 years.³ Additional risk factors include female sex and polypharmacy.¹ Here, we present a case in which a young man developed severe (≤128 mmol/L) hyponatremia after starting mirtazapine.⁴

Case Report

The patient was a 30-year-old man with a history of major depressive disorder, generalized anxiety disorder, and focal frontal lobe epilepsy, who was admitted to the inpatient psychiatry unit for suicidal ideation. Prior to this admission, the patient was not prescribed any psychiatric medications, although he was engaged in psychotherapy. He had completed a short trial of sertraline 3 years prior to this admission, which was discontinued after a few days due to diarrhea and restlessness.

On admission, the patient’s home regimen of cenobamate 150 mg daily, clobazam 15 mg nightly, oxcarbazepine 900 mg twice daily, and omeprazole 20 mg daily was continued. Admission laboratory values were notable for a serum sodium level of 131 mmol/L (normal range, 136–145) and osmolality of 250 mosm/kg (normal range, 276–304), as well as a positive urine drug screen for tetrahydrocannabinol. In the year prior to this admission, his sodium levels had been moderately low, ranging from 129 to 136 mmol/L. The neurology department was consulted due to moderate hyponatremia thought to be secondary to oxcarbazepine, and it was recommended to avoid adjustments to antiepileptic medications. His last known seizure was 11 months prior to this admission, and he had no change in his medications during the last 4 months.

On hospital day 2, mirtazapine was started at 15 mg nightly to treat mood symptoms. This dose was increased to 30 mg nightly on hospital day 3. On day 5, a metabolic panel revealed a sodium level of 121 mmol/L, prompting discontinuation of mirtazapine and transfer to the medical floor. Serum osmolality decreased slightly to 248 mosm/kg, and urine sodium and osmolality were within normal limits, consistent with SIADH per Bartter and Schwartz criteria.⁵ The patient denied symptoms of hyponatremia, and his cognition appeared to be at baseline. With a 1-L fluid restriction and decrease of oxcarbazepine dose to 750 mg twice daily, the patient’s sodium level rose to 132 mmol/L on hospital day 7, and he was discharged home in stable condition.

Discussion

This case highlights the importance of closely monitoring sodium levels when starting any antidepressant in patients taking oxcarbazepine. Mirtazapine has been found to carry a significantly lower risk of SIADH compared to other antidepressant classes (1.02%, compared to 7.44% in serotonin-norepinephrine reuptake inhibitors and 5.59% in selective serotonin reuptake inhibitors).⁶ Despite this, the additive effects of mirtazapine and existent moderate SIADH attributable to oxcarbazepine likely caused this severe hyponatremia (probable cause per Naranjo Adverse Drug Reaction Probability Scale).⁷ Concurrent use of a proton pump inhibitor may have further increased the risk for SIADH.¹ To date, there are no known studies, to our knowledge, that have specifically explored the additive effects of oxcarbazepine and mirtazapine. A 2001 study concluded that carbamazepine, a structural analog of oxcarbazepine, and mirtazapine together were not associated with significant adverse effects in a population of young, healthy males.⁸ However, oxcarbazepine carries a higher risk of SIADH (19.4% incidence), so further study may be warranted.^4,9 With a limited evidence base currently available to guide clinical decisions, we recommend close monitoring of electrolytes and reduction of polypharmacy if possible when starting any antidepressant in patients taking oxcarbazepine, even if young and medically stable.

Article Information

Published Online: July 16, 2026. https://doi.org/10.4088/PCC.26cr04199
© 2026 Physicians Postgraduate Press, Inc.
Prim Care Companion CNS Disord 2026;28(4):26cr04199
Submitted: January 29, 2026; accepted March 26, 2026.
To Cite: Luzum NR, Munjal S. Mirtazapine-induced severe hyponatremia in a young man taking oxcarbazepine. Prim Care Companion CNS Disord 2026;28(4):26cr04199.
Author Affiliations: Department of Psychiatry, Wake Forest University School of Medicine, Winston-Salem, North Carolina (Luzum, Munjal).
Corresponding Author: Nathan Luzum, MD, Department of Psychiatry, Wake Forest University School of Medicine, 1 Medical Center Blvd, Winston-Salem, NC 27103
([email protected]).
Financial Disclosure: None.
Funding/Support: None.
Patient Consent: Consent was received from the patient to publish the case report, and information has been de-identified to protect patient anonymity.