Clinical trial NCT05008939: Sevoflurane for Treatment-Resistant Depression
Official title: Subanesthetic Sevoflurane for Treatment-Resistant Depression: A Proof-of-Concept Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Depressive Disorder, Treatment-Resistant
Depressive Disorder, Major
Keywords: treatment-resistant depression (TRD)
major depressive disorder (MDD)
sevoflurane
Lead sponsor: Shanghai First Maternity and Infant Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai Pudong New Area Mental Health Center
First posted: 2021-08-17
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study intends to carry out a prospective, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of subanesthetic sevoflurane for treatment-resistant depression.


Eligibility criteria: Inclusion Criteria:

1. age 18-65 years
2. meeting DSM-V criteria for major depressive disorder
3. a pretreatment score ≥17 on HDRS-17
4. meeting criteria for TRD, defined as having had at least two adequate dose-duration antidepressant medication failures in the current depressive episode.
5. current treatment drugs were stably used for at least 4 weeks

Exclusion Criteria:

1. MDD with psychosis, e.g., bipolar disorder, schizophrenia, schizoaffective disorder, obsessive-compulsive disorder, panic disorder, et al
2. Drug, tobacco or alcohol abuse
3. active suicidal intention
4. previous administration of NMDA receptor antagonists (e.g., ketamine)
5. previous (\<6 weeks prior) or ongoing treatment with electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS)
6. pregnancy or breastfeeding
7. morbidly obese, BMI\>35kg/m2
8. other diseases that could interfere with the results

Primary outcomes:
measure: Rates of treatment responses in 17-item Hamilton Depression Rating Scale (HDRS-17)
timeFrame: 24 hours after the end of treatment
Secondary outcomes:
measure: Rates of treatment responses in HDRS-17
timeFrame: 2 hours, 7 days,14 days and 28 days after the end of treatment
measure: Rates of remissions in HDRS-17
timeFrame: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
measure: Rates of treatment responses in Montgomery-Åsberg Depression Rating Scale (MADRS)
timeFrame: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
measure: Rates of remissions in MADRS
timeFrame: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
measure: The assessment of depression with self-rating scale
timeFrame: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
measure: The assessment of anxiety by psychiatrist
timeFrame: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
measure: The assessment of anxiety with self-rating scale
timeFrame: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
measure: The assessment of improvement by psychiatrist
timeFrame: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
measure: The assessment of improvement with self-rating scale
timeFrame: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
measure: The assessment of side effects with self-rating scale
timeFrame: 2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
measure: Side effects of sevoflurane
timeFrame: up to 2 hours after the end of treatment
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine
state: Shanghai
Study officials:
affiliation: Department of Anesthesiaology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine
name: Zhiqiang Liu, MD
role: STUDY_CHAIR
References:
citation: Gaynes BN, Warden D, Trivedi MH, Wisniewski SR, Fava M, Rush AJ. What did STAR*D teach us? Results from a large-scale, practical, clinical trial for patients with depression. Psychiatr Serv. 2009 Nov;60(11):1439-45. doi: 10.1176/ps.2009.60.11.1439.
citation: Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L, Norquist G, Howland RH, Lebowitz B, McGrath PJ, Shores-Wilson K, Biggs MM, Balasubramani GK, Fava M; STAR*D Study Team. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006 Jan;163(1):28-40. doi: 10.1176/appi.ajp.163.1.28.
citation: Mrazek DA, Hornberger JC, Altar CA, Degtiar I. A review of the clinical, economic, and societal burden of treatment-resistant depression: 1996-2013. Psychiatr Serv. 2014 Aug 1;65(8):977-87. doi: 10.1176/appi.ps.201300059.
citation: Papakostas GI, Petersen TJ, Farabaugh AH, Murakami JL, Pava JA, Alpert JE, Fava M, Nierenberg AA. Psychiatric comorbidity as a predictor of clinical response to nortriptyline in treatment-resistant major depressive disorder. J Clin Psychiatry. 2003 Nov;64(11):1357-61. doi: 10.4088/jcp.v64n1112.
citation: Collins PY, Patel V, Joestl SS, March D, Insel TR, Daar AS; Scientific Advisory Board and the Executive Committee of the Grand Challenges on Global Mental Health; Anderson W, Dhansay MA, Phillips A, Shurin S, Walport M, Ewart W, Savill SJ, Bordin IA, Costello EJ, Durkin M, Fairburn C, Glass RI, Hall W, Huang Y, Hyman SE, Jamison K, Kaaya S, Kapur S, Kleinman A, Ogunniyi A, Otero-Ojeda A, Poo MM, Ravindranath V, Sahakian BJ, Saxena S, Singer PA, Stein DJ. Grand challenges in global mental health. Nature. 2011 Jul 6;475(7354):27-30. doi: 10.1038/475027a. No abstract available.
citation: Berlim MT, Turecki G. Definition, assessment, and staging of treatment-resistant refractory major depression: a review of current concepts and methods. Can J Psychiatry. 2007 Jan;52(1):46-54. doi: 10.1177/070674370705200108.
citation: Sanacora G, Schatzberg AF. Ketamine: promising path or false prophecy in the development of novel therapeutics for mood disorders? Neuropsychopharmacology. 2015 Mar 13;40(5):1307. doi: 10.1038/npp.2014.338. No abstract available.
citation: Chen C, Ji M, Xu Q, Zhang Y, Sun Q, Liu J, Zhu S, Li W. Sevoflurane attenuates stress-enhanced fear learning by regulating hippocampal BDNF expression and Akt/GSK-3beta signaling pathway in a rat model of post-traumatic stress disorder. J Anesth. 2015 Aug;29(4):600-8. doi: 10.1007/s00540-014-1964-x. Epub 2014 Dec 23.
citation: Zhang H, Li L, Sun Y, Zhang X, Zhang Y, Xu S, Zhao P, Liu T. Sevoflurane prevents stroke-induced depressive and anxiety behaviors by promoting cannabinoid receptor subtype I-dependent interaction between beta-arrestin 2 and extracellular signal-regulated kinases 1/2 in the rat hippocampus. J Neurochem. 2016 May;137(4):618-29. doi: 10.1111/jnc.13613. Epub 2016 Mar 31.
citation: Luo C, Zhang YL, Luo W, Zhou FH, Li CQ, Xu JM, Dai RP. Differential effects of general anesthetics on anxiety-like behavior in formalin-induced pain: involvement of ERK activation in the anterior cingulate cortex. Psychopharmacology (Berl). 2015 Dec;232(24):4433-44. doi: 10.1007/s00213-015-4071-2. Epub 2015 Sep 24.
citation: Guo Z, Zhao F, Wang Y, Wang Y, Geng M, Zhang Y, Ma Q, Xu X. Sevoflurane Exerts an Anti-depressive Action by Blocking the HMGB1/TLR4 Pathway in Unpredictable Chronic Mild Stress Rats. J Mol Neurosci. 2019 Dec;69(4):546-556. doi: 10.1007/s12031-019-01380-2. Epub 2019 Jul 31.