Sevoflurane for Treatment-Resistant Depression

Depressive Disorder, Major Clinical Trial

Official title:

Subanesthetic Sevoflurane for Treatment-Resistant Depression: A Proof-of-Concept Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05008939
• Other study ID #: ShanghaiFMIH2021 Zhiqiang Liu
• Status: Not yet recruiting
• Phase: N/A
• Start date: August 2021
• Est. completion date: March 2022

Study information

• Verified date: August 2021
• Source: Shanghai First Maternity and Infant Hospital
• Contact: Fuyi Shen, MD
• Phone: 86-13524123072
• Email: shenfuyi315[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 15
• Est. completion date: March 2022
• Est. primary completion date: March 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Depressive Disorder, Treatment-Resistant
• Disease

Intervention

Drug:
• Sevoflurane
Patients receive 1% sevoflurane and 30% oxygen for 1 hour.
• Placebo
Patients received 30% oxygen for 1 hour.

Locations

Country	Name	City	State
China	Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai First Maternity and Infant Hospital	Shanghai Pudong New Area Mental Health Center

Country where clinical trial is conducted

China, 

References & Publications (11)

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. Review. — View 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-3ß 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. — View 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. — View 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. — View 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. — View 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. — View 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. Review. — View 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. — View 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. — View 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. — View 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 ß-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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rates of treatment responses in 17-item Hamilton Depression Rating Scale (HDRS-17)	=50% HDRS-17 reduction in depressive symptoms	24 hours after the end of treatment
Secondary	Rates of treatment responses in HDRS-17	=50% HDRS-17 reduction in depressive symptoms	2 hours, 7 days,14 days and 28 days after the end of treatment
Secondary	Rates of remissions in HDRS-17	HDRS-17 =7 points	2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
Secondary	Rates of treatment responses in Montgomery-Åsberg Depression Rating Scale (MADRS)	=50% MADRS reduction in the baseline score	2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
Secondary	Rates of remissions in MADRS	MADRS <10	2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
Secondary	The assessment of depression with self-rating scale	The changes of score in Patient Health Questionnaire-9 (PHQ-9)	2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
Secondary	The assessment of anxiety by psychiatrist	The changes of score in Hamilton Anxiety Rating Scale (HAMA)	2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
Secondary	The assessment of anxiety with self-rating scale	The changes of score in Generalized Anxiety Disorder Screener (GAD-7)	2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
Secondary	The assessment of improvement by psychiatrist	The changes of score in Clinical Global Impression (CGI)	2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
Secondary	The assessment of improvement with self-rating scale	The changes of score in Patient Global Impressions of Improvement (PGI-I)	2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
Secondary	The assessment of side effects with self-rating scale	Including Patient Rated Inventory of Side Effects (PRISE)	2 hours, 24 hours, 7 days,14 days and 28 days after the end of treatment
Secondary	Side effects of sevoflurane	Including nausea, vomiting, headache, dizzy, hypotension, hypoxemia, carbon dioxide accumulation, et al	up to 2 hours after the end of treatment