Accelerated Intermittent Theta Burst Stimulation for Inpatients With Major Depressive Disorder (aiTBS)

• Change in Montgomery Asberg Depression Rating Scale (MADRS) score[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
  A 10-item clinician-administered scale, designed to be particularly sensitive to antidepressant treatment effects in patients with major depression. Severity gradations for the MADRS have been proposed: 9-17 = mild depression, 18-34 = moderate depression, and ≥ 35 = severe depression. Scores range from 0-60.
• Change in Scale of Suicidal Ideation (SSI) score[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
  19-item clinician administered assessment to measure the intensity, pervasiveness, and characteristics of suicidal ideation in adults. Scores range from 0-38.
• Change in resting-state recordings and TMS-evoked potentials in EEG data.[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
  For the first and last stimulation session, EEG recording will be made before (resting-state EEG) and during (TMS-evoked potentials) the stimulation.
• Change in Quick Inventory Depressive Scale-Self Reported (QIDS) score[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
  Self-report measure of depressive symptoms. The questionnaire consists of 16 questions. Each question can score between 0 to 4 points. Severity of depression is determined as follows: 0=None, 1=Mild, 2=Moderate, 3=Severe, 4=Very Severe. Total scores range from 0-27. Total scores: 0-5= no depression, 6-10= mild depression, 11-15= moderate depression, 16-20= severe depression, 21-27= very severe depression. The total score is obtained by adding the scores for each of the nine symptom domains of the DSM-IV MDD criteria: depressed mood, loss of interest or pleasure, concentration/decision making, self-outlook, suicidal ideation, energy/fatigability, sleep, weight/appetite change, and psychomotor changes (Rush et al. 2003).
• Change in Pittsburgh Insomnia Rating Scale-20 Item Version (PIRS-20) score[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
  Self-report, 20 item scale to determine patient's insomnia level. Each question can be scored between 0-3. 0=not bothered at all slightly bothered moderately bothered severely bothered Total score is calculated by adding up all questions (i.e. Q1+Q2+...Q20). One missing item is allowed, pro-rate if missing one item....i.e. (sum/count)*20. Minimum Score = 0 (good); Maximum Score = 60 (bad)
• Change in performance on the NIH toolbox[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
  Neurocognitive assessments delivered through an iPad app
• Biomarker analysis in patient blood (plasma) samples[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
  Blood (plasma) samples will be collected before and one month after stimulation. Blood collection is conducted by the registered hospital phlebotomist (following same protocol of a routine blood test). Blood samples will be analyzed by our collaborators at the Open Medicine Institute. Specifically, samples will be used for DNA/RNA extraction and analyses will be done to determine potential gene targets. Presence of inflammatory markers (cytokines) will also be determined. All analyses of blood samples will be conducted in the Open Medicine Institute.
• Biomarker analysis in patient stool samples[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
  Stool samples will be collected before and one month after stimulation. Stool collection is performed by registered hospital nurses. Stool samples will be analyzed by our collaborators at the Open Medicine Institute. Specifically, stool samples will be analyzed for potential biomarkers in the gut microbiome. All analyses of stool samples will be conducted in the Open Medicine Institute.
• Biomarker analysis in patient saliva samples[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
  Saliva samples will be collected before and one month after stimulation. Saliva collection is performed by registered study personnel. Saliva samples will be analyzed by our collaborators at the Open Medicine Institute. Specifically, saliva samples will be analyzed for cortisol levels. All analyses of stool samples will be conducted in the Open Medicine Institute.
• Change in Bush-Francis Catatonia Rating Scale (BFCRS).[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
  A clinician administered assessment of catatonia. The Bush-Francis Catatonia Rating Scale (BFCRS) is a standardized, quantifiable examination of catatonia designed to screen and diagnose the possibility of catatonia. The BFCRS consists of a 23-item rating scale with the first 14 items comprising the Bush Francis Catatonia Screening Instrument (BFCSI). For screening, items 1-14 are marked as absent (0) or present (3). The presence of two or more of the screening items for 24 hours or longer meets the diagnosis for catatonia proposed by Bush et al. For severity, items 1-23 are rated using a scale of 0-3. The total BFCRS score is the sum of responses to all 23 items.
• Change in the Quality of Life Enjoyment and Satisfaction Questionnaire-short form score (Q-LES-Q-SF)[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
  15-item self-report questionnaire where each item is scored from very poor=1 to very good=5. The scoring of the Q-LES-Q-SF involves summing only the first 14 items to yield a raw total score. The last two items are not included in the total score but are stand-alone items. The raw total score ranges from 14 (min) to 70 (max).
• Change in Immediate Mood Scaler (Ims-12) score[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
  Immediate Mood Scaler (IMS) is a newly developed, iPad-deliverable 12-item self-report tool designed to capture current mood states. Scores range from bad=0 to good=7, for each item.
• Change in Columbia Suicide Severity Rating Scale (C-CSSRS)[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
  A trained rater will administer the Columbia Suicide Severity Rating Scale (C-CSSRS). This questionnaire was developed to rate suicidal ideation and behavior. It rates a person's degree of suicidal ideation on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent and behaviors. The scale identifies specific behaviors which may be indicative of a person's intent to complete suicide. An person exhibiting even a single behavior identified by the scale was 8 to 10 times more likely to complete suicide.
• Change in heart rate[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
  Measure presence of any change in heart rate variability
• Change in Temporal Experience of Pleasure Scale (TEPS)[ Time Frame: After all stimulation sessions have been completed (approximately 48 hours after the final session) ]
  The Temporal Experience of Pleasure Scale (TEPS) is a measure specifically designed to capture the anticipatory and consummatory facets of pleasure. TEPS is an 18-item questionnaire. Each item is scored from 0 "very false for me" to 6 "very true for me". Total score ranges from 0 to 108.

This study evaluates an accelerated schedule of theta-burst stimulation for inpatients with major depressive disorder

• Device: Accelerated theta burst stimulation
  All participants will receive iTBS (intermittent theta burst stimulation), either to the left DLPFC or ACC. Stimulation intensity will be individualized according to the individual's resting motor threshold.

• Active Comparator: Dorsolateral prefrontal cortex
  The accelerated theta burst stimulation protocol will be applied to the dorsolateral prefrontal cortex (dlPFC)
• Active Comparator: Anterior cingulate cortex
  The accelerated theta burst stimulation protocol will be applied to the anterior cingulate cortex (ACC)