Efficacy of Deep Anaesthesia With Isoflurane as a Fast-response Antidepressant Agent

NCT ID: NCT04171193

Last Updated: 2019-11-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-31
• Study Completion Date: 2020-12-31

Brief Summary

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.

Detailed Description

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.

Conditions

Depressive Disorder, Major; Treatment Resistant Depression; Depressive Episode

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ISO

Patients not taking oral medications for depression. They will receive the study intervention consisting in general anesthesia with the volatile anesthetic gas Isoflurane until burst suppression is detected in electroencephalogram more than 80% of the time for 15 minutes.

Group Type: EXPERIMENTAL

Isoflurane

Intervention Type: DRUG

Deep anesthesia with isoflurane to achieve burst suppression pattern for more than 80% of the time for 15 minutes measured in electroencephalogram and Bi-Spectral Index

ISOAD

Patients in treatment with oral medications for depression, will receive intervention consisting in general anesthesia with the volatile anesthetic gas Isoflurane until burst suppression is detected in electroencephalogram more than 80% of the time for 15 minutes

Group Type: EXPERIMENTAL

Isoflurane

Intervention Type: DRUG

Deep anesthesia with isoflurane to achieve burst suppression pattern for more than 80% of the time for 15 minutes measured in electroencephalogram and Bi-Spectral Index

ISOPOT

Patients that where from ISO arm, that did not respond to intervention consisting in general anesthesia with the volatile anesthetic gas Isoflurane until burst suppression is detected in electroencephalogram more than 80% of the time for 15 minutes They will now, start taking sertraline as oral medication for depression to asset the enhancement of oral treatment after Isoflurane challenge.

Group Type: EXPERIMENTAL

Sertraline Pill

Intervention Type: DRUG

Patients that did not respond to Isoflurane treatment, will star on sertraline to evaluate any enhancement in antidepressant efficacy after pre-treatment with isoflurane

Interventions

Isoflurane

Deep anesthesia with isoflurane to achieve burst suppression pattern for more than 80% of the time for 15 minutes measured in electroencephalogram and Bi-Spectral Index

Intervention Type: DRUG

Sertraline Pill

Patients that did not respond to Isoflurane treatment, will star on sertraline to evaluate any enhancement in antidepressant efficacy after pre-treatment with isoflurane

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundação de Amparo à Pesquisa do Estado de São Paulo

OTHER_GOV

Sponsor Role: collaborator

University of Sao Paulo

OTHER

Sponsor Role: lead

Responsible Party

Ricardo Alberto Moreno, M.D., Ph.D.

DIRECTOR: MOOD DISORDERS UNIT (GRUDA)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ricardo Alberto Moreno, Phd

Role: STUDY_DIRECTOR

Instituto de Psiquiatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

Locations

Insitute of Psychiatry of the University of São Paulo

São Paulo, , Brazil

Countries

Brazil

Central Contacts

Tiago Gil, MD

Role: CONTACT

Tiagogil@gmail.colm

5511983817707

Other Identifiers

19921719.9.0000.0068

Identifier Type: OTHER

Identifier Source: secondary_id

ISORADAR

Identifier Type: -

Identifier Source: org_study_id