A 69-year-old woman was hospitalized due to progressive lethargy with hyperammonemia. Five months before the current admission, she was diagnosed with depression based on her low level of daily physical activity and thus began taking antidepressants. Abdominal computed tomography revealed a portosystemic shunt running between the left renal vein and inferior mesenteric vein. Balloon-occluded retrograde transvenous obliteration of the shunt vessel was performed, and the patient showed a remarkable clinical improvement. The possibility of a portosystemic shunt should be considered in the presence or absence of underlying liver disease and the ammonia level should be measured before diagnosing depression, as portosystemic encephalopathy may be reversible with interventional radiology treatment.