Major Depressive Disorder
Conditions
Keywords
Adolescent Depression, Transcranial Magnetic Stimulation
Brief summary
This research study aims to test the safety and effectiveness of repetitive transcranial magnetic stimulation (rTMS) on teens with depression. The study also seeks to understand how rTMS treatment affects the neurobiology of teens with depression.
Detailed description
This study aims to: 1. Evaluate the antidepressant effect and safety of rTMS in adolescents meeting criteria for major depressive disorder, single or recurrent episode. 2. Evaluate, by proton magnetic resonance spectroscopy (1H-MRS) at 3 Tesla (3T), the regional specificity \[anterior cingulate (AC) vs. left dorsolateral prefrontal cortex (L-DLPFC)\] of cerebral metabolites (glutamate and glutamine) in adolescent depression and study whether glutamine resonances are associated with response or remission of clinical depressive symptoms when rTMS is used to treat adolescent depression. 3. Evaluate the accuracy of an efficient method for locating the F3 position (i.e., L-DLPFC) through comparison with magnetic resonance imaging (MRI).
Interventions
DEVICETranscranial Magnetic Stimulation
30 daily treatments of (over 6-8 weeks) of 10 Hz rTMS at 120% motor threshold, applied to the left dorsolateral prefrontal cortex with 3,000 stimulations per treatment
Sponsors
Paul E. Croarkin
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of unipolar major depressive disorder, in a current major depressive episode, without psychotic features * Pretreatment CDRS-R Raw score ≥ 40 * Age is at least 13 and less than 19 years * Ongoing, stable dose antidepressant therapy for at least 6 weeks to include the following antidepressants (with dosing range): * Celexa (citalopram hydrobromide) - 10 to 60mg * Cymbalta (duloxetine) - 40mg to 120mg * Desyrel (trazodone HCl) - 12.5mg to 150mg * Effexor (venlafaxine HCl) - 37.5mg to 300mg * Luvox (fluvoxamine maleate) - 25mg to 200mg * Lexapro (escitalopram oxalate) - 10mg to 40mg * Paxil (paroxetine HCl) - 10mg to 50mg * Pristiq (desvenlafaxine) - 50mg to 100mg * Prozac (fluoxetine HCl) - 10mg to 80mg * Remeron (mirtazapine) - 7.5mg to 45mg * Zoloft (sertraline HCl) - 25mg to 200mg * Subjects able to attend at least 31 study visits at Mayo Clinic - Rochester * Willing to provide informed assent (adolescent) and informed consent (family)
Exclusion criteria
* Subjects currently on stimulant, antipsychotic, bupropion or tricyclic antidepressant medications. * Prior rTMS, vagus nerve stimulation (VNS) or electroconvulsive therapy (ECT) * Contraindication to MRI * Contraindication to rTMS (history of neurological disorder such as seizures, increased intracranial pressure, brain surgery, or head trauma with loss of consciousness for \>15 minutes, history of stroke, family history of epilepsy, intracardiac lines, Anticoagulant, immune suppressive and/or chemotherapy, or those who received any of these therapies within 3 months before enrollment in the study Unstable medication conditions such as hematological or infectious (e.g., human immunodeficiency virus-HIV) disorders, implanted electronic device, metal in the head, or pregnancy) * History of schizophrenia, schizoaffective disorder, other \[non mood disorder\] psychosis, depression secondary to a medical condition, mental retardation, substance dependence or abuse within the past year (except nicotine), bipolar disorder, psychotic features in this or previous episodes, amnestic disorder, obsessive compulsive disorder, post-traumatic stress disorder, panic disorder * History of autoimmune, endocrine, viral, or vascular disorder. * Unstable cardiac disease, uncontrolled hypertension, or sleep apnea * Active suicidal intent or plan, or history of attempt within the past 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Children's Depression Rating Scale-Revised (CDRS-R) Post Treatment 30 or Last Treatment (in Cases of Early Withdrawal) | 5 days of Treatment 30 or Last Treatment | The Children's Depression Rating Scale-Revised (CDRS-R) is a validated, 17-item, semi-structured clinician rating tool to assess severity of depression with subject and parental input for 14 of the 17 items. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression - Severity (CGI-S) Post Treatment 30 or Last Treatment (in Cases of Early Withdrawal) | Within 5 days of Treatment 30 or Last Treatment | The Clinical Global Impression - Severity (CGI-S) is a standardized assessment utilizing a 7-point scale with which the clinician rates severity of the subject's depressive illness at the time of assessment relative to the clinician's past experience with patients with the same diagnosis. Range of scale is 1-7 (1= normal, not ill at all; 7= among the most ill patients; larger number indicates greater severity of symptoms or worse outcome). |
| The Clinical Global Impression - Improvement (CGI-I) | Within 5 days of 30 treatments or after last treatment in case of early withdrawal | The Clinical Global Impression - Improvement (CGI-I) is a standardized assessment utilizing a 7-point scale with which the clinician rates improvment of the subject's depressive illness at the time of assessment relative to the clinician's past experience with patients with the same diagnosis. Range of scale is 1-7 (1= very much improved, 7=very much worse) larger number indicates greater severity of symptoms or worse outcome). |
Countries
United States
Participant flow
Recruitment details
10 participants recruited(and enrolled) from the Mayo Clinic Child and Adolescent Mood Disorders Clinic.
Pre-assignment details
Participants were maintained on stable dosage of antidepressant medication for 4 weeks prior to enrollment and rTMS treatment.
Participants by arm
| Arm | Count |
|---|---|
| Transcranial Magnetic Stimulation Open-label course of 30 daily treatments with repetitive transcranial magnetic stimulation (rTMS) at 120% magnetic field intensity relative to the patient's resting motor threshold, at 10 pulses per second (10 Hz) for 4 seconds, with an intertrain interval of 26 seconds for a total of 75 trains per treatment session.
Transcranial Magnetic Stimulation | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | 1 participant had scalp discomfort | 1 |
| Overall Study | 1 participant had worsening depression | 1 |
| Overall Study | 1 participant went back to school | 1 |
Baseline characteristics
| Characteristic | Transcranial Magnetic Stimulation |
|---|---|
| Age, Categorical <=18 years | 10 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 15.9 years STANDARD_DEVIATION 1.1 |
| Children's Depression Rating Scale Revised | 62.9 units on a scale STANDARD_DEVIATION 8.2 |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Children's Depression Rating Scale-Revised (CDRS-R) Post Treatment 30 or Last Treatment (in Cases of Early Withdrawal)
The Children's Depression Rating Scale-Revised (CDRS-R) is a validated, 17-item, semi-structured clinician rating tool to assess severity of depression with subject and parental input for 14 of the 17 items.
Time frame: 5 days of Treatment 30 or Last Treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Transcranial Magnetic Stimulation | Children's Depression Rating Scale-Revised (CDRS-R) Post Treatment 30 or Last Treatment (in Cases of Early Withdrawal) | 41.8 units on a scale | Standard Deviation 13.2 |
Secondary
Clinical Global Impression - Severity (CGI-S) Post Treatment 30 or Last Treatment (in Cases of Early Withdrawal)
The Clinical Global Impression - Severity (CGI-S) is a standardized assessment utilizing a 7-point scale with which the clinician rates severity of the subject's depressive illness at the time of assessment relative to the clinician's past experience with patients with the same diagnosis. Range of scale is 1-7 (1= normal, not ill at all; 7= among the most ill patients; larger number indicates greater severity of symptoms or worse outcome).
Time frame: Within 5 days of Treatment 30 or Last Treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Transcranial Magnetic Stimulation | Clinical Global Impression - Severity (CGI-S) Post Treatment 30 or Last Treatment (in Cases of Early Withdrawal) | 3.4 units on a scale | Standard Deviation 1.5 |
Secondary
The Clinical Global Impression - Improvement (CGI-I)
The Clinical Global Impression - Improvement (CGI-I) is a standardized assessment utilizing a 7-point scale with which the clinician rates improvment of the subject's depressive illness at the time of assessment relative to the clinician's past experience with patients with the same diagnosis. Range of scale is 1-7 (1= very much improved, 7=very much worse) larger number indicates greater severity of symptoms or worse outcome).
Time frame: Within 5 days of 30 treatments or after last treatment in case of early withdrawal
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Transcranial Magnetic Stimulation | The Clinical Global Impression - Improvement (CGI-I) | 2.7 units on a scale | Standard Deviation 1.1 |