The purpose of this study is to determine the efficacy and any possible side effects of focal electrically administered seizure therapy (FEAST) as a treatment intervention for patients with recurrent and treatment resistant depression.

Recurrent and treatment resistant depression (TRD) has high morbidity and escalating costs for the healthcare system and society at large. Electroconvulsive therapy (ECT) remains the most effective acute antidepressant treatment for TRD, but with significant risks of cognitive impairment. The efficacy and side effects of conventional ECT are contingent on the anatomic positioning of electrodes and stimulus dosage. A technique that could spatially target the prefrontal cortex may preserve the efficacy of ECT while simultaneously reducing cognitive side effects.

The investigators have recently demonstrated that focal electrically-administered seizure therapy [FEAST], which markedly improves the spatial targeting of the electrical current, is feasible in adult TRD individuals. FEAST can initiate seizures focally and specifically in the prefrontal cortex prior to secondary seizure generalization. Preliminary results in depressed humans at Columbia University and later at the Medical University of South Carolina (MUSC) generated by the PI (Nahas) show that these focal seizures produce clinically meaningful antidepressant responses. Additional work is needed to refine the technique and compare it to conventional approaches.

In this study, the investigators will further develop FEAST to achieve clinically meaningful remission rates (at least 50% of subjects). 30 TRD patients (or 20 with a complete record) will undergo an open-label course of FEAST for an adaptive number of total sessions designed to maximize efficacy of the technique. The investigators will use a dosing paradigm using a current level of 800 mA, finalize the electrode sizes, and test, at one treatment session, the effects of reversing the directionality of current flow on site of seizure induction. Patients will also undergo electroencephalography (EEG) assessments to characterize the induced seizures' spatial and temporal distributions. The investigators will obtain time to orientation recovery as a marker of potential longer-term cognitive side effects.

This technique could fundamentally change and improve the most effective antidepressant treatment, while simultaneously minimizing or eliminating the major side-effects that prohibit larger adoption of ECT.

Inclusion Criteria:

• Age between 18 and 90 years (inclusive)
• Diagnosis of major depressive disorder (unipolar or bipolar) [SCID to derive RDC; DSM-IV]
• Pretreatment HRSD score ≥ 18 [Hamilton Rating Scale for Depression (24-item)]
• ECT indicated [Physician evaluation]
• Willing and capable of providing informed consent [Physician evaluation]

Exclusion Criteria:

• History of schizophrenia, schizoaffective disorder, other functional psychosis, or rapid cycling bipolar disorder [SADS to derive RDC; rapid cycling defined as ≥ four episodes in past year]
• History of neurological illness or insult other than conditions associated with psychotropic exposure (e.g., tardive dyskinesia) [Physician evaluation; medical history]
• Alcohol or substance abuse or dependence in the past year (RDC) [Physician evaluation]
• Secondary diagnosis of a delirium, dementia, or amnestic disorder (DSM-IV), pregnancy, or epilepsy [Physician evaluation]
• Requires especially rapid antidepressant response due to suicidality, psychosis, inanition, psychosocial obligations, etc. [Physician evaluation]
• Unable to tolerate psychotropic washout and no psychotropic medication during the ECT trial, other than lorazepam (up to 3 mg/d PRN) [Treatment history and physician evaluation]
• ECT in the past six months [Physician evaluation; medical history]
• Has a cardiovascular and/or pulmonary condition [Physician evaluation]