Background: Vortioxetine, known for its efficacy in treating depression through its effects on various neurotransmitters, has not been previously reported to induce syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Case Presentation: This case report describes a 74‐year‐old man with major depressive disorder who developed SIADH 1 week after starting treatment with vortioxetine. SIADH is characterized by symptoms such as headache, nausea, disorientation, and seizures, stemming from hyponatremia (123 mEq/L), without dehydration or edema. Vortioxetine was discontinued, and an alternative drug, mianserin, was initiated. The patient was restricted from drinking water due to hyponatremia. The serum Na concentration improved over time to within the normal range by the second week after admission. Conclusion: This is the first case report of vortioxetine‐induced SIADH. This report documents the first known case where vortioxetine, a medication for depression, caused a rare side effect: Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH) in a 74‐year‐old male patient. Within a week of starting vortioxetine, the patient experienced symptoms like headache, nausea, confusion, and seizures, attributable to low blood sodium levels. Upon discontinuing vortioxetine and switching to another antidepressant, the patient's condition normalized within two weeks. This case highlights a significant association between vortioxetine and SIADH. [ABSTRACT FROM AUTHOR]