Depression
Conditions
Keywords
Adolescent, Depression, rTMS
Brief summary
The objective of this investigation is to examine the safety and feasibility of a series of repetitive transcranial magnetic stimulation (rTMS) treatments (10 Hertz \[Hz\]; Left Dorsolateral Prefrontal Cortex), with a Neuronetics Model 2100 Therapy System as adjuvant treatment for depression in adolescent subjects.
Detailed description
High frequency rTMS applied to the left dorsolateral prefrontal cortex (L-DLPFC) has been shown to have an antidepressant effect. Initial studies comparing electroconvulsive therapy (ECT) and rTMS suggest that rTMS has been as effective as ECT in treating non-psychotic depression. Given the high degree of ongoing dysfunction in depressed adolescents despite optimization of treatment with antidepressant medications, new concerns regarding suicidal thoughts and behaviors in adolescents treated with antidepressant medications, and the more interventional nature of ECT, the use of rTMS as adjuvant therapy may be of significant clinical benefit. Thus far, research using rTMS to treat depression in adolescents has been limited. The primary aim of this study is to examine the safety and feasibility of using 10 Hz rTMS applied to the left dorsolateral prefrontal cortex (L-DLPFC) as adjuvant treatment for depression in adolescents.
Interventions
DEVICErTMS Treatment
Active rTMS treatment.
Sponsors
Eli Lilly and Company
Mayo Clinic
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
Yes
Inclusion criteria
* Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) diagnosis of unipolar major depression without psychosis. * Current or past history of lack of response to at least two adequate antidepressant trials selective serotonin re-uptake inhibitors (SSRI) operationally defined using the Antidepressant Treatment History Form (ATHF) * Children's Depression Rating Scale-Revised (CDRS-R) score of 40 or higher at baseline * At least six weeks of ongoing SSRI therapy at a stable dose. * SSRI Medications will include: * Citalopram (Celexa, Cipramil, Emocal, Sepram) * Escitalopram oxalate (Lexapro, Cipralex, Esertia) * Fluoxetine (Prozac, Fontex, Seromex, Seronil, Sarafem, Fluctin (EUR)) * Fluvoxamine maleate (Luvox, Faverin) * Paroxetine (Paxil, Seroxat, Aropax, Deroxat) * Sertraline (Zoloft, Lustral, Serlain) * Age 13-18 years. * Outpatient, inpatient, or partial hospitalization patients. * Capable of providing informed assent/consent (in addition to parent/guardian consent).
Exclusion criteria
* Current Diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, mental retardation, pervasive developmental disorder, somatoform disorder, dissociative disorder, posttraumatic stress disorder, obsessive-compulsive disorder, eating disorders, antecedents of autism, and all personality disorders. * Active substance dependence (except nicotine) in the past 12 months. * Subjects with a history of head trauma, unprovoked seizure history, seizure disorder, or family history of treatment resistant epilepsy. * Suspected pregnancy or pregnancy as confirmed by a urine pregnancy test at screening. * History of failure to respond to ECT. * Metal in the head (except in the mouth), implanted medication pump, cardiac pacemaker. * Prior brain surgery. * Risk for increased intracranial pressure such as brain tumor. * Unable to obtain motor threshold in the subject or motor threshold too high, such that 120% MT cannot be obtained (i.e. \>84% of device output). * Significant change or increase in antidepressant medications within the last six weeks. * Change in psychiatrist, psychologist, or therapist within the last four weeks. * Suicide attempt within the past three months. * Any suicide attempt or suicidal intent during the study will terminate involvement in this study. * Subjects currently on stimulant, antipsychotic, atypical antidepressant or tricyclic antidepressant medications. * Unstable medical or neurological conditions that may include hematological, infectious (such as Human immunodeficiency virus \[HIV\] positive patients) metabolic, or cardiovascular conditions that may preclude safe participation in trial. * Subjects undergoing anticoagulant, immune suppressive and 1 or chemotherapy, or those who received any of these therapies \</=3 months before enrollment in the study * Subjects with intra-cardiac lines
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Cognitive Status as Measured by the Children's Auditory Verbal Learning Test 2 (CAVLT-2) | Pre-treatment (baseline visit) and post treatment (approximately 6-8 weeks after baseline visit) | The Children's Auditory Verbal Learning Test 2 (CAVLT-2) is a neuropsychological test that measures auditory verbal learning and memory. This test is designed for ages 6.6-17.11 years. Scores are reported as normalized standard scores. The minimum standard score is 60 and the maximum 140; a higher score indicates a better performance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Level of Depression at Visit 30, as Measured by the Children's Depression Rating Scale, Revised (CDRS-R) | At study visit 30 | The Children's Depression Rating Scale, Revised (CDRS-R) is a validated, 17-item, clinician rating tool to assess severity of depression. Parents provide input into 14 of the items. Scores range from 0 to 60, with the following scale: not depressed (\<20), borderline depressive symptoms (20-29), mild depression (30-39), moderate depression (40-59), severe depression (\>/=60). |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from clinical and community referrals at 3 participating sites. The study took place from May 2007 to October 2009.
Participants by arm
| Arm | Count |
|---|---|
| Active Treatment All subjects will have active rTMS treatment (10Hz, L-DLPFC - 3,000 Stimulations/treatment) | 8 |
| Total | 8 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Active Treatment |
|---|---|
| Age, Categorical <=18 years | 8 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age Continuous | 16.5 years STANDARD_DEVIATION 1.18 |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
Change in Cognitive Status as Measured by the Children's Auditory Verbal Learning Test 2 (CAVLT-2)
The Children's Auditory Verbal Learning Test 2 (CAVLT-2) is a neuropsychological test that measures auditory verbal learning and memory. This test is designed for ages 6.6-17.11 years. Scores are reported as normalized standard scores. The minimum standard score is 60 and the maximum 140; a higher score indicates a better performance.
Time frame: Pre-treatment (baseline visit) and post treatment (approximately 6-8 weeks after baseline visit)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rTMS Treatment | Change in Cognitive Status as Measured by the Children's Auditory Verbal Learning Test 2 (CAVLT-2) | -11.3 units on a scale | Standard Deviation 12.98 |
Secondary
Mean Level of Depression at Visit 30, as Measured by the Children's Depression Rating Scale, Revised (CDRS-R)
The Children's Depression Rating Scale, Revised (CDRS-R) is a validated, 17-item, clinician rating tool to assess severity of depression. Parents provide input into 14 of the items. Scores range from 0 to 60, with the following scale: not depressed (\<20), borderline depressive symptoms (20-29), mild depression (30-39), moderate depression (40-59), severe depression (\>/=60).
Time frame: At study visit 30
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rTMS Treatment | Mean Level of Depression at Visit 30, as Measured by the Children's Depression Rating Scale, Revised (CDRS-R) | 33.3 units on a scale | Standard Deviation 7.3 |