2026 ECNP Congress

PS02-2106

Emergence of treatment-resistant depression after epilepsy surgery: a case report and mechanistic considerations on limbic network disruption

Ibrahim Akbas — E. Erol Canbazoglu · Basaksehir Cam and Sakura City Hospital, Department of Psychiatry, Istanbul, Türkiye

2026 ECNP Congress

Objectives

Epilepsy surgery is an effective treatment option, particularly in patients with drug-resistant temporal lobe epilepsy[1]. However, despite favorable outcomes in terms of reduced seizure frequency and intensity, psychiatric adverse outcomes remain an important clinical concern in this population. Depressive and anxiety disorders are among the most commonly observed psychiatric comorbidities both before and after surgical intervention [2]. Postoperative mood disturbances, particularly depression, represent clinically significant yet often underrecognized conditions.

The development of these disorders may be related to collateral damage to limbic structures, including the hippocampus and amygdala, which play a central role in affective regulation and emotional processing [3]. Surgical alterations involving these structures may contribute to the emergence of postoperative psychiatric disturbances. This case report presents a patient with treatment-resistant depression following epilepsy surgery involving resection of the left hippocampus and amygdala due to drug-resistant mesial temporal lobe epilepsy.

Case Presentation

A 28-year-old male presented to the psychiatry outpatient clinic with persistent fatigue, anhedonia, reduced motivation, and diminished interest in daily activities. He had a history of drug-resistant epilepsy and underwent epilepsy surgery in 2017 based on neuroimaging findings consistent with left mesial temporal sclerosis. Postoperative magnetic resonance imaging (MRI) confirmed resection of the left hippocampus and amygdala, consistent with a left anterior temporal lobectomy.

Depressive symptoms emerged immediately after the surgical intervention, with no documented history of depressive disorder prior to surgery. The patient had previously been treated with multiple antidepressants, including escitalopram, sertraline, and clomipramine, administered at adequate doses and durations, without significant clinical improvement. Augmentation strategies with aripiprazole, olanzapine, and buspirone were also attempted but yielded insufficient response.

At the time of evaluation, he had been receiving fluoxetine 60 mg/day and mirtazapine 30 mg/day for two months, in combination with three antiepileptic medications. The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HAM-D), with a total score of 26, indicating severe depression. Based on the inadequate response to multiple antidepressant trials and augmentation strategies, the clinical presentation was consistent with treatment-resistant depression.Following clinical evaluations, the patient was referred to a medical board for disability assessment due to functional impairment.

The temporal association between epilepsy surgery and the onset of depressive symptoms, along with involvement of mesial temporal structures, suggests a possible link between limbic system disruption and persistent depressive symptomatology.

Discussion

The long-term cognitive, psychiatric, and psychosocial outcomes of epilepsy surgery remain incompletely understood [4]. This case highlights treatment-resistant depression following resection of mesial temporal structures, particularly the hippocampus and amygdala. Although epilepsy surgery is effective for seizure control, postoperative psychiatric complications may significantly affect quality of life.

Resection of these limbic structures may lead to long-term disruption of mood-related circuits [5]. In this case, the limited response to multiple antidepressant and augmentation strategies may be associated with iatrogenic alterations within limbic networks. Early recognition of postoperative depressive disorders is essential, as timely psychiatric intervention may improve outcomes. Delayed diagnosis may lead to prolonged morbidity and functional impairment. Early psychosocial support, structured rehabilitation, and evaluation of disability-related support systems are essential in management.

References

  1. Wiebe S, Blume WT, Girvin JP, Eliasziw M. A randomized, controlled trial of surgery for temporal-lobe epilepsy. N Engl J Med. 2001;345(5):311–318.
  2. Kanner AM. Depression in epilepsy: a complex relation. Epilepsy Behav. 2003;4(2):S21–S26.
  3. LeDoux JE. Emotion circuits in the brain. Annu Rev Neurosci. 2000;23:155–184.
  4. Jobst BC, Cascino GD. Resective epilepsy surgery for drug-resistant focal epilepsy. JAMA. 2015;313(3):285–293.
  5. Wrench JM, Wilson SJ, Bladin PF, Reutens DC. Hippocampal volume and depression: insights from epilepsy surgery. J Neurol Neurosurg Psychiatry. 2009;80(5):539–544.