pBFS-guided High-dose TMS Over DMPFC for Treatment-resistant Major Depressive Disorder

Inclusion Criteria:

• DSM-5 diagnosis of depressive disorder, recurrent episodes;
• A total score of at least 20 on the HAMD-17 and Montgomery-Asberg Depression RatingScale;
• Aged 18-65 years, female or male;
• Inadequate response to at least one antidepressant trial of adequate doses andduration;
• The MSM (Maudsley Staging Method) score ≥ 7;
• Stable antidepressant regimen for at least 4 weeks before treatment;
• Understand the trial and sign the informed consent.

Exclusion Criteria:

• Meet DSM-5 diagnostic criteria for other mental disorders (such as schizophreniaspectrum disorders, bipolar and related disorders, neurodevelopmental disorders,neurocognitive disorders, or depressive disorders due to substances and/ormedications, depressive disorders due to other medical problems, etc.);
• Patients with a cardiac pacemaker, cochlear implant, or other metal foreign body andany electronic equipment implanted in the body, patients with claustrophobia and othercontraindications to magnetic resonance scanning, and patients with contraindicationsto rTMS treatment;
• Patients with serious or unstable diseases of the cardiovascular, liver, kidney,blood, endocrine, neurological system, and other systems or organs, especially thosewith organic brain diseases (such as ischemic stroke, cerebral hemorrhage, braintumor, etc.) and a history of severe brain trauma as judged by the researcher;
• History of epilepsy (presence of at least 2 uninduced seizures more than 24 hoursapart, or diagnosis of the epileptic syndrome, or seizures within the past 12 months);Or currently received medications or other treatments that will lower the seizurethreshold;
• History of ECT, rTMS, VNS, DBS, tDCS, light therapy, or other physical therapy relatedto mental illness within 3 months;
• Currently receiving or planning to start formal cognitive or behavioral therapy, orsystemic psychological therapy (interpersonal therapy, dynamic therapy, cognitivebehavioral therapy, etc.) during the trial.
• Substance abuse or dependence (including alcohol, drugs, and other psychoactivesubstances) in the past 1 year;
• The female of childbearing potential who plans to become pregnant during the trial,and that is pregnant or breastfeeding.
• Patients in any clinical trials of other drugs or physical therapy within 1 monthbefore the screening.
• First-degree relatives have bipolar affective disorder.
• Difficulty or inability to engage in normal communication, understand or followinstructions, and cooperate with treatment and evaluators.
• Investigators think that was inappropriate to participate.