Use of Repetitive Transcranial Magnetic Stimulation for Major Depressive Disorder in the Context of a Comorbid Delusional Disorder.

We present a case of repetitive transcranial magnetic stimulation (rTMS) use to treat a 38-year-old male with initial diagnostic uncertainty between major depressive disorder (MDD) with psychotic features and MDD with co-occurring delusional disorder, persecutory type. This patient reported a long-standing history of depressive symptoms and recent onset of paranoid delusions. Prior to receiving rTMS, the patient was treated for three years with a combination of antidepressants, antipsychotics, and cognitive behavioral therapy for psychosis. During this period, his delusions persisted irrespective of changes in mood symptoms, confirming his diagnosis of MDD with co-occurring delusional disorder. He received rTMS for severe, treatment-refractory depression that worsened in the setting of psychosocial stressors. Following treatment, his mood symptoms significantly improved while his paranoid beliefs persisted. This case is significant due to treatment planning difficulty given initial diagnostic uncertainty between MDD with psychotic features and MDD with co-occurring delusional disorder. Additionally, paranoia and delusions respond poorly to current psychotropic medication and psychotherapy treatment options. This case highlights the need for better treatment for delusions and the importance of iteratively assessing treatment response and updating patient formulation when navigating diagnostic uncertainty. In this clinical challenge, experts discuss considerations in differentiating MDD with psychotic features and MDD with co-occurring delusional disorder. Additionally, they weigh implications for rTMS treatment candidacy, evidence supporting rTMS for psychotic disorders, the role of psychotherapy in treating paranoia, and the neural circuits involved in persecutory delusions.