BACKGROUND: Major Depressive Disorder (MDD) is a common mental health illness, characterized by persistent feelings of sadness, diminished interests, guilt, low-self esteem, and disturbances in sleep and appetite. A significant percentage of patients with MDD are treatment resistant. Electroconvulsive Therapy (ECT) is a biological procedure utilized for treatment resistant illnesses. Diagnosis and clinical conditions primarily dictate when ECT is the appropriate treatment modality for an individual. Circumstances requiring rapid clinical response, risks affiliated with alternative treatments, resistance to pharmacotherapy, and medical history are all factors that designate ECT as the treatment of choice. METHODS: The objective of this systematic review was to examine how different anesthetics or combinations of agents affect ECT’s therapeutic efficacy in depressed, adult patients. Electroencephalography (EEG) and motor seizure durations and Hamilton Depression Rating Scale (HDRS) scores were used as primary measures of clinical outcomes. Two rounds of literature searches were conducted in the PubMed, Web of Science, and Google Scholar databases to identify randomized controlled trials and crossover trials that examined the effects of different intravenous sedatives and hypnotic agents on ECT. Two reviewers independently evaluated the internal validity and quality of studies, extracted data, and analyzed statistics. Utilizing all relevant data, standardized mean differences (SMD) with 95% confidence intervals (CIs), and heterogeneity measures were calculated. Ten studies with 373 participants were included. RESULTS: Thiopental only anesthesia was associated with longer EEG seizure duration when compared to propofol only treatment. The pooled effect size from studies with propofol anesthesia also suggests that this agent is associated with shorter seizure durations. If assessed individually with thiopental, the combination of ketamine and thiopental is correlated with increased motor as well as EEG seizure durations. When pooled; however, studies with patient groups assigned to anesthesia consisting of ketamine and another primary agent do not show significant differences either in EEG or motor seizure durations. Additionally, no difference exists in HDRS score reductions between propofol and methohexital. Of note; however, ketamine combined with either propofol or thiopental had significantly greater decreases in HDRS scores. CONCLUSION: Choice of anesthetic should be determined based on anticipated clinical outcome, adverse effect profile, reemergence, and patient preference. If long seizures are preferred, thiopental may be a reasonable option. However, if significantly larger decreases in depression score are preferred, then the combinations of ketamine and propofol or ketamine and thiopental appear to be the therapies of choice. Small sample sizes and insufficient clinical data limit the interpretations of these variables that determine therapeutic efficacy. Larger randomized control trials and crossover trials would provide greater insight into the optimal use of intravenous anesthetic agents with minimal adverse effects.