Abstract: Over the past decade, the Diagnostic and Statistical Manual’s method of prescribing medications based on presenting symptoms has been challenged. The shift toward precision medicine began with the National Institute of Mental Health and culminated with the World Psychiatric Association’s posit that paradigm shift is needed. This study supports that shift by providing evidence explaining the high rate of psychiatric medication failure and suggests a possible first step toward precision medicine. A large psychiatric practice began collecting electroencephalograms (EEGs) for this study in 2012. The EEGswere analyzed by the same neurophysiologist (board certified IN electroencephalography) on 1,233 patients. This study identified 4 EEGbiomarkers accounting for medication failure in refractory patients: focalslowing, spindling excessive beta, encephalopathy, and isolated epileptiformdischarges. Each EEG biomarker suggests underlying brain dysregulation, whichmay explain why prior medication attempts have failed. The EEG biomarkerscannot be identified based on current psychiatric assessment methods, anddepending upon the localization, intensity, and duration, can all present ascomplex behavioral or psychiatric issues. The study highlights that the EEGbiomarker identification approach can be a positive step toward personalizedmedicine in psychiatry, furthering the clinical thinking of “testing the organwe are trying to treat.”