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.

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