Major depressive disorder Mental and Behavioural Disorders
Conditions
Interventions
Participants will be randomly allocated to one of two groups:
Treatment as usual (TAU): half of participants will continue with their standard care, such as psychotherapy and/or antidepressant medica
Sponsors
King's College London
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. Adults aged 18 years or over 2. Current episode of depression based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria (APA, 2013) for major depressive disorder (MDD) as assessed by structured clinical assessment, Mini-International Neuropsychiatric Interview (MINI) 3. Having at least a moderate severity of depressive symptoms as measured by a score of at least 18 in MADRS 4. Either not taking antidepressant medication or taking a stable dose of antidepressant medication for at least 6 weeks before enrolment. 5. Either not currently in psychotherapy or engaged in ongoing psychotherapy for at least 6 weeks before enrolment. 6. Being under the care of a GP 7. Agreeable for GP to be regularly informed about study participation 8. Able to provide written, informed consent
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 22/01/2026: 1. Significant suicide risk as measured by answering 'yes' to questions 4, 5 or 6 on the Columbia Suicide Severity Rating Scale (C-SSRS) Screen 2. Primary comorbid psychiatric disorder (e.g. obsessive compulsive disorder) based on DSM-5 criteria as assessed in MINI 3. Current daily use of medications that affect cortical excitability (e.g. benzodiazepines) 4. Current illicit drug use or heavy alcohol use with high risk of alcohol use disorder as measured by a score of 8 or more in the Alcohol Use Disorders Identification Test consumption (AUDIT-C) 5. History of electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), cranial electrotherapy stimulation (CES), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), or other brain stimulation 6. History of esketamine / ketamine for treatment of depression 7. History of psychosurgery for depression 8. Having cognitive impairment (e.g. dementia) 9. Current medical disorder or neurological disorder that may mimic mood disorder (e.g. hormonal disorder, unstable heart disease) 10. Have any implants in the brain or neurocranial defect 11. Have shrapnel or any ferromagnetic material in the head 12. Have any active implantable medical device (e.g. pacemaker) 13. If female and of child-bearing potential, currently pregnant or planning to become pregnant during the study 14. Concurrent enrolment in another interventional study Previous exclusion criteria: 1. Significant suicide risk as measured by answering 'yes' to questions 4, 5 or 6 on the Columbia Suicide Severity Rating Scale (C-SSRS) Screen 2. Primary comorbid psychiatric disorder (e.g. obsessive compulsive disorder) based on DSM-5 criteria as assessed in MINI 3. Current daily use of medications that affect cortical excitability (e.g. benzodiazepines) 4. Current illicit drug use or heavy alcohol use with high risk of alcohol use disorder as measured by a score of 5 or more in the Alcohol Use Disorders Identification Test consumption (AUDIT-C) 5. History of electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), cranial electrotherapy stimulation (CES), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), or other brain stimulation 6. History of esketamine / ketamine for treatment of depression 7. History of psychosurgery for depression 8. Having cognitive impairment (e.g. dementia) 9. Current medical disorder or neurological disorder that may mimic mood disorder (e.g. hormonal disorder, unstable heart disease) 10. Have any implants in the brain or neurocranial defect 11. Have shrapnel or any ferromagnetic material in the head 12. Have any active implantable medical device (e.g. pacemaker) 13. If female and of child-bearing potential, currently pregnant or planning to become pregnant during the study 14. Concurrent enrolment in another interventional study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Clinician-rated depressive symptom severity measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) at 10-week end of treatment period | — |
Secondary
| Measure | Time frame |
|---|---|
| Key secondary outcome: Clinician-rated depressive symptoms measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) at 6 months Additional secondary outcomes: 1. Self-rated depressive symptoms measured by Montgomery-Åsberg Depression Rating Scale-Self report (MADRS-S). at 10-week end of treatment period 2. Clinician-rated depressive symptoms, as measured by the Hamilton Depression Rating Scale (HDRS). at 10-week end of treatment period 3. Clinician-rated anxiety symptoms measured by the Hamilton Anxiety Rating Scale (HAMA). at 10-week end of treatment period 4. Treatment response at 10-week end of treatment period, measured by participants with 50% or more improvement on MADRS rating from baseline 5. Treatment remission at 10-week end of treatment period, as measured by participants with a MADRS rating of 10 or less 6. Self-rated depressive symptoms measured by Montgomery-Åsberg Depression Rating Scale-Self report (MADRS-S) at 6 months 7. Clinician-rated depressive symptoms measured by the Hamilton Depression Rating Scale (HDRS) at 6 months 8. Clinician-rated anxiety symptoms measured by the Hamilton Anxiety Rating Scale (HAMA) at 6 months 9. Sustained treatment response at 6 months, measured by participants with 50% or more improvement on MADRS rating from baseline 10. Sustained treatment remission at 6 months, measured by participants with a MADRS rating of 10 or less. | — |
Countries
England, United Kingdom
Outcome results
None listed