1.Understand the molecular mechanisms of Treatment-Resistant Depression (TRD) and the associated prefrontal cortex-related brain networks. 2.Investigate the effects of novel glutamatergic treatments and core molecular mechanisms by administering low doses of Ketamine or S-Ketamine (Esketamine) +/- GABA-A agonists in TRD patients. 3.Study the heritability and polygenic risks associated with Treatment-Resistant Depression (TRD).
Conditions
Interventions
In the first and second years, the Ketamine study will be conducted, followed by the Esketamine study in the third and fourth years. Ketamine Group: A total of 48 participants will be enrolled and ra
Sponsors
Grant of Taipei Veterans General Hospital, Taiwan
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Treatment-Resistant Depression (TRD): Must have a well-documented history confirming that the patient has not responded to at least two different antidepressants (including Selective Serotonin Reuptake Inhibitors, SSRIs) at adequate doses and treatment durations. Depression severity is assessed with the 17-item Hamilton Depression Rating Scale (HDRS-17), with a score of 18 or above, and the Clinical Global Impression-Severity (CGI-S) scale with a score of 4 or above.
Exclusion criteria
Exclusion criteria: 1.Previously met the DSM-IV criteria for Bipolar Disorder, Schizophrenia, or Dementia. 2.History of major medical or surgical illnesses or neurological disorders; or currently has physical conditions that the investigator deems unsuitable for this treatment (e.g., severe hypertension, severe cardiovascular disease, severe liver or kidney dysfunction, or other physical abnormalities that the investigator considers unsuitable for this treatment). 3.History of alcohol and drug abuse. 4.Presence of metallic implants or other implants that may interfere with EEG signals. 5.Substance dependence or abuse within the past six months (e.g., cocaine, cannabis, opioids, ketamine, MDMA). 6.Current use of NMDA receptor antagonist medications (e.g., Amantadine, Rimantadine, Lamotrigine, Memantine, Dextromethorphan). 7.Pregnant subjects. 8.Other conditions that prevent cooperation, such as being deemed unsuitable after screening or refusal to sign the informed consent form. 9.Previously underwent Ketamine treatment with no antidepressant effect. 10.Exclusion of subjects with strong suicidal ideation within the past week, as indicated by a score of 4 on the third item of the Hamilton Depression Rating Scale (suicidality).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| According to three different conditions, we divided the whole study into three parts, each with a corresponding primary outcome. 1. Compare the differences in functional connectivity, brain glucose metabolism activity, and brain wave patterns between patients with Treatment-Resistant Depression and other subjects in prefrontal cortex-related brain regions. 2. Compare the differences in antidepressant effects both between and within groups treated with novel glutamatergic drugs. 3. Identify the SNP loci associated with Treatment-Resistant Depression and use Polygenic Risk Scoring (PRS) to predict the risk of siblings developing Treatment-Resistant Depression | — |
Countries
Asia(except Japan)
Contacts
Public ContactCheng-Ta Li
Taipei Veterans General Hospital, Taiwan Department of Psychiatry
Outcome results
None listed