Prolonged Post–Electroconvulsive Therapy Delirium in Treatment-Resistant Depression With Central Nervous System Risk Factors Under Programmed Cell Death Protein 1 Inhibitor Therapy

We report a diagnostically challenging case of treatment-resistant depression (TRD) in a 52-year-old woman with multiple factors potentially increasing susceptibility to central nervous system (CNS) adverse effects, including global cortical atrophy, concomitant lithium and antipsychotic treatment, and ongoing programmed cell death protein 1 (PD-1) inhibitor therapy. After failing multiple pharmacological and neuromodulatory treatments, electroconvulsive therapy (ECT) was initiated. While ECT led to marked clinical improvement, the patient developed a prolonged delirium after the 12th session, lasting 7 to 10 days, initially raising concern for autoimmune encephalitis under immunotherapy. A comprehensive diagnostic work-up including electroencephalography (EEG), contrast-enhanced magnetic resonance imaging (MRI), and lumbar puncture (LP) found no evidence of nonconvulsive status epilepticus (NCSE), acute structural pathology, or florid autoimmune encephalitis, despite borderline SOX1 antibody reactivity in CSF. Cognition returned to baseline without specific therapy, and follow-up paired serum/CSF testing was negative for SOX1 antibodies. The episode was considered a multifactorial delirium, with ECT as one likely contributing factor alongside concomitant medication, structural brain changes, and PD-1 inhibitor therapy. Following relapse, maintenance ECT was resumed using a modified protocol without recurrence of prolonged delirium. This case highlights that ECT may remain an option in carefully selected complex patients when accompanied by structured diagnostic work-up and interdisciplinary monitoring.