In this study the investigators will submit patients with treatment resistant depression to deep anesthesia with isoflurane to get 15 minutes of cortical burst suppression on electroencephalogram, once a week for six weeks. The follow up will be for 6 months. The aim is to evaluate the change in depression severity during the entire period.

This study protocol will measure the efficacy of deep anesthesia, until burst suppression rate of 80% or more measured with Bi-spectral Index (BIS), with the volatile anesthetic Isoflurane. The investigators will select 30 subjects. The participants will be separated into 2 arms of 15 individuals. One arm called ISOAD will keep the oral treatment with antidepressants. The second arm, called ISO, will do a washout of any oral medications for depression. Both groups will go under six sessions, once per week, of deep anesthesia and will be followed up for 6 months to evaluate the survival of the antidepressant effect, if any effect happens. Before the anesthesia occurs, blood samples will be drawn to measure Brain-derived neurotrophic factor and investigators will apply depression rating scales such as MADRS and Hamilton - 17 , Young mania Scale, UKU scale for side effects, electroencephalogram will be recorder to be compared with the data shown on BIS. All the anesthesia procedure will be done with induction with propofol, fentanyl and muscular relaxant, to facilitate the tracheal intubation and compliance with the mechanical ventilator,based on body weight in standard dosages. Isoflurane will be set to 2,4% ( 2 cam) until Burst suppression rate >80% is achieve. Then the anesthesia will be maintained for 15 minutes, then the flow of anesthetic gas will be ended and the patient will be allowed to awake and discharged home when the anesthesiologist decide based on Aldrete Kroulik scale. After the 6th session the participant will return in one week to final evaluation. All the patients that shows improvement in depression scores will enter the phase 2 with one visit every 15 days for 2 months and then once a month until the 6th month. The non responders of the ISO group will start oral antidepressant sertraline to evaluate any potentialization effect of the intervention and be allocated in ISOPOT group. Those from ISOAD group (Isoflurane plus oral antidepressants) that did not respond to the intervention will be discontinued from the study and their data used in the study as non-responders. Those from ISOPOT group that did not improve their depression scores after 4 weeks will be discontinued from the study and the data computed as non-responders.

Inclusion Criteria:

• Patients with Treatment resistant depression on depressive state with or without psychiatric comorbidities for anxious features
• moderate to severe condition measured by Montgomery Asperger Depression Rating Scale and Hamilton Depression rating scale - 17
• be between 18 and 60 years old
• IF female, do not be pregnant and use a trustable contraceptive method
• can read and write in Portuguese language
• will to be in all the phases of the study
• have agreed with free will to participate
• classified as American Society of Anesthesiologists - Physical Status 1 or 2 by a certified anesthesiologist
• Suicide ideation measured by Montgomery Asperger Depression Rating Scale on item 10 less than 4

Exclusion Criteria:

• drug abusers in the last 6 months, except for nicotine
• use of benzodiazepines or lamotrigine less then 15 days from the first session
• family history of malignant hyperthermia Suicidal ideation on item 10 of Montgomery Asperger Depression Rating Scale more than 4
• Suicide attempt one month prior the study begins