Clinical trial NCT04171193: Efficacy of Deep Anaesthesia With Isoflurane as a Fast-response Antidepressant Agent
Official title: Efficacy of Deep Anaesthesia With Isoflurane as a Fast-response Antidepressant Agent in Treatment Resistant Depression Patients : Proof of Concept
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Depressive Disorder, Major
Treatment Resistant Depression
Depressive Episode
Keywords: Isoflurane
Anesthesia
Treatment resistant depression
Deep anesthesia
Burst suppression
Depressive episode
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
Collaborators: name: Fundação de Amparo à Pesquisa do Estado de São Paulo
First posted: 2019-11-20
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: We will have two groups, one arm with oral antidepressants and other arm without oral antidepressants, no placebo, no control. Everyone receives the intervention. Those who respond to treatment, will be followed for 24 weeks, those who do not respond, if not in the oral antidepressant group, will star oral antidepressants and be followed for 24 weeks
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Reduction in Depression severity - MADRS
timeFrame: Six days after the last session
measure: Reduction in Depression - HDRS 17
timeFrame: Six days after the last session
Secondary outcomes:
measure: Udvalg for Kliniske Undersøgelser - side effects rating scale
timeFrame: From 6th day after the first intervention up to week 24th
measure: Change in Depression severity MADRS
timeFrame: From 6th day after the intervention up to week 24th
measure: Change in Depression severity HDRS17
timeFrame: From 6th day after the intervention up to week 24th
measure: Magnitude MADRS
timeFrame: From 6th day after the intervention up to week 24th
measure: Magnitude HDRS 17
timeFrame: From 6th day after the intervention up to week 24th
measure: Survival of the effect - HDRS 17
timeFrame: After the 6th session through 24th week
measure: Survival of the effect - MADRS
timeFrame: After the 6th session through 24th week
measure: Enhance HDRS 17
timeFrame: After the 10th visit through the 24th week
measure: Enhance MADRS
timeFrame: After the 10th visit through the 24th week
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Insitute of Psychiatry of the University of São Paulo
Study officials:
affiliation: Instituto de Psiquiatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
name: Ricardo Alberto Moreno, Phd
role: STUDY_DIRECTOR
References: