Missing the Forest for the Trees: Delayed Diagnosis and Management of Treatment Resistant Schizophrenia

We present a case of a 36-year-old female with schizophrenia, coronary artery disease, and type 2 diabetes who was hospitalized for altered mental status and persistent psychosis. Initial evaluation revealed myocardial infarction, pulmonary embolism, and urinary tract infection. While delirium resolved with treatment, psychotic symptoms persisted. Brain MRI showed diffuse cortical microhemorrhages, prompting extensive workup for vasculitis, infection, and prothrombotic syndromes, all of which were negative. Despite multiple antipsychotic trials (quetiapine, risperidone, ziprasidone), the patient remained symptomatic, with a PANSS score of 156, consistent with treatment-resistant schizophrenia (TRS). The patient was started on clozapine that was later augmented with electroconvulsive therapy (ECT). After 10 ECT sessions and clozapine titrated to 300 mg daily, her PANSS score improved significantly to 60. This case highlights the diagnostic complexity in medically ill psychiatric patients and the risk of delayed TRS diagnosis. Early use of standardized tools like PANSS in the general medical setting may be useful in differentiating psychiatric from medical causes and can expedite treatment. Though clozapine remains first-line for TRS, 45-70% may not respond to monotherapy.^5,6,7 ECT augmentation was effective in our case, but evidence remains mixed,⁹ highlighting the need for further research into optimal TRS augmentation strategies.