Study of Repetitive Transcranial Magnetic Stimulation (rTMS) in Depressed Teens

• Change from baseline in Children's Depression Rating Scale (CDRS-R) [ Time Frame: At treatment 10 (~2 weeks), treatment 20 (~4 weeks), 1 month following treatment 30, and 6 months following treatment 30 ] [ Designated as safety issue: Yes ]
  A validated, 17-item, semi-structured clinician rating tool to assess severity of depression with parents providing input into 14 of the items. The specific unit of measure will be change in mean CDRS-R scores from baseline.
• Change from Baseline in Quick Inventory of Depressive Symptoms (QIDS-A17) [ Time Frame: At treatment 10 (~2 weeks), treatment 20 (~4 weeks), and 6 months following treatment 30 ] [ Designated as safety issue: Yes ]
  A 17-item, self-report instrument. The specific unit of measure will be change in mean QIDS-A17 scores from baseline.
• Change from baseline in Proton Magnetic Resonance Spectroscopy (H-MRS) [ Time Frame: At treatment 10 (~2 weeks), treatment 20 (~4 weeks), and 6 months following treatment 30 ] [ Designated as safety issue: Yes ]
  The specific unit of measure will be change in mean metabolite levels (i.e., glutamate, glutamine, and glutamate+glutamine (Glx) from baseline.
• Change from baseline in Clinical Global Impression—Severity & Improvement (CGI-S & CGI-I) [ Time Frame: At treatment 10 (~2 weeks), treatment 20 (~4 weeks), and 6 months following treatment 30 ] [ Designated as safety issue: Yes ]
  Standardized clinician assessments rating illness severity and change over time. The specific unit of measure will be change in mean CGI-S & CGI-I scores from baseline

• Mean change from baseline in Clinical Global Impression - Severity (CGI-S) post Treatment 30 or Last Treatment (in cases of early withdrawal) [ Time Frame: Within 5 days of Treatment 30 or Last Treatment ] [ Designated as safety issue: Yes ]
  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.
• Mean change from baseline in Clinical Global Impression - Improvement (CGI-I) post Treatment 30 or Last Treatment (in cases of early withdrawal) [ Time Frame: Within 5 days of Treatment 30 or Last Treatment ] [ Designated as safety issue: Yes ]
  The Clinical Global Impression - Improvement (CGI-I) is a standardized assessment utilizing a 7-point scale with which the clinician rates the degree to which the severity of the subject's depressive illness has improved or worsened compared to baseline severity.

• Change from baseline in the Delis-Kaplan Executive Function Scale (D-KEFS) [ Time Frame: At 6 months following treatment 30 ] [ Designated as safety issue: Yes ]
  Measures flexibility of thinking on a visual motor task and a verbal fluency test to measure fluent productivity in verbal domain. The specific unit of measure will be change in mean D-KEFS score from baseline
• Change from baseline in Children's Auditory Verbal Learning Test (CAVLT-2) [ Time Frame: At 6 months following treatment 30 ] [ Designated as safety issue: Yes ]
  Measures auditory verbal learning and memory. The specific unit of measure will be change in mean CAVLT-2 score from baseline
• Change from baseline in the Autobiographical Memory Interview (AMI) [ Time Frame: At 6 months following treatment 30 ] [ Designated as safety issue: Yes ]
  Samples the subject's recollections across three broad time periods. The specific unit of measure will be change in mean AMI score from baseline

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.

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).

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