University of Iowa Interventional Psychiatry Service Patient Registry

Study Overview
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Brief Summary
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The purpose of this study is to examine the effects of interventional/procedural therapies for treatment-resistant depression (TRD) and Obsessive-Compulsive Disorder (OCD). These treatments include electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), racemic ketamine infusion and intranasal esketamine insufflation. The investigators will obtain various indicators, or biomarkers, of a depressed individuals' state before, during, and/or after these treatments. Such biomarkers include neurobehavioral testing, neuroimaging, electroencephalography, cognitive testing, vocal recordings, epi/genetic testing, and autonomic nervous system measures (i.e. fight-or-flight response). The results obtained from this study may provide novel antidepressant treatment response biomarkers, with the future goal of targeting a given treatment to an individual patient (personalized medicine).

Detailed Description
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Treatment response biomarkers in TRD and OCD have been and will remain an active area of research. Interventional treatments in psychiatry, e.g. ECT, TMS, racemic ketamine infusions and intranasal esketamine insufflations, offer exciting opportunities for biomarker discovery due their procedural nature (obviating concerns for treatment non-adherence in non-supervised settings), more rapid-onset, and larger effect sizes than typically seen with traditional antidepressant medications or evidence-based psychotherapies. Although no well-replicated TRD biomarkers have been approved for standard clinical use, several potential biomarkers have been investigated across multiple modalities, i.e. neuroimaging(1,2), autonomic function(3,4), genetics(5-7), electroencephalography (EEG) (8,9), and computational analysis of behavior or speech(10). These studies have promising early results but often insufficient predictive power at the subject-level. The investigators anticipate that combinatorial, multimodal biomarkers will enhance predictive power and, as a result, improve treatment personalization in major depression. The University of Iowa Interventional Psychiatry Service Patient Registry systematically collects data from TRD and OCD patients undergoing procedural treatment(s) for major depression. First, the investigators seek to replicate and/or extend discoveries from prior investigations, e.g. TMS-induced autonomic changes as positive predictors of antidepressant efficacy. The investigators will also compare and contrast differences, not only in response to a given therapy, but also how individual subjects respond across different treatment modalities, e.g. how does functional connectivity in the brain change in response to an effective course of TMS as opposed to ECT? Such findings could inform the future development of clinical guidelines; this is especially critical as some of these treatment modalities have only recently been approved for TRD by the U.S. Food and Drug Administration, e.g. intermittent theta burst stimulation (iTBS) and intranasal esketamine insufflation and dTMS for OCD. Next, a longitudinal database may also be valuable for future biomarker discovery and/or replication in independent samples, i.e. an epigenetic signature of antidepressant treatment response to an interventional modality identified by another research group. Similarly, this patient registry could be valuable for collaborative research with other institutions administering interventional treatments in psychiatry.

Official Title
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University of Iowa Interventional Psychiatry Service Patient Registry

Conditions
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Treatment Resistant Depression, Major Depressive Episode, Major Depression, Major Depressive Disorder, Bipolar Disorder, Bipolar Depression, Obsessive-Compulsive Disorder

Intervention / Treatment
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* Device: Electroconvulsive Therapy (ECT)
* Device: Transcranial Magnetic Stimulation (TMS)
* Drug: Ketamine
* Drug: Esketamine
* Device: Deep Transcranial Magnetic Stimulation (dTMS)


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: 18-99 years of age English-speaker with a level of understanding sufficient to agree to clinical treatment with a treatment modality offered by the Interventional Psychiatry Service, all required research procedures, and sign an informed consent document Clinical diagnosis of a major depressive episode in the context of major depressive disorder or bipolar disorder or treatment-resistant OCD evaluated by a provider on the Interventional Psychiatry Service and felt to be an appropriate candidate for clinical treatment with a treatment modality offered by the Interventional Psychiatry Service. EXCLUSION CRITERIA: Age less than 18 years A primary neuropsychiatric diagnosis that is not either major depressive disorder or bipolar disorder Serious, unstable medical conditions/problems including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, neurologic, immunologic, or hematologic disease, e.g. uncontrolled asthma, uncontrolled hyper/hypothyroidism or active cancer. Involuntary commitment to psychiatry inpatient units If patients have one or more of the following MRI Exclusion criteria, they will not be able to participate in those aspects of this study: The presence of an implanted device including pacemaker, coronary stent, defibrillator, or neurostimulation device that is not MRI-compatible The presence of ferromagnetic objects in the body, i.e. bullets, shrapnel, and/or metal slivers Clinically-significant claustrophobia Clinically-significant hearing loss Pregnant or nursing women or women of child bearing potential not using at least one medically accepted means of contraception (to include oral, injectable, or implant birth control, condom or diaphragm with spermicide, intrauterine devices (IUD), tubal ligation, abstinence, or partner with vasectomy) The presence of any medical illness likely to alter brain morphology and/or physiology (e.g., hypertension, diabetes) even if controlled by medications

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Major Depressive Episode<br>After referral to the University of Iowa's Interventional Psychiatry Clinic, the patient will be clinically evaluated and, if appropriate, commence the procedural-based treatment course. | Device: Electroconvulsive Therapy (ECT)<br>* ECT for the treatment of treatment-resistant depression OR Bipolar Disorder in an active major depressive episode<br>Device: Transcranial Magnetic Stimulation (TMS)<br>* TMS for the treatment of treatment-resistant depression in an active major depressive episode<br>Drug: Ketamine<br>* Intravenous ketamine infusion for the treatment of treatment-resistant depression in an active major depressive episode<br>Drug: Esketamine<br>* Intranasal esketamine insufflation for the treatment of treatment-resistant depression in an active major depressive episode<br>Device: Deep Transcranial Magnetic Stimulation (dTMS)<br>* TMS for the treatment of OCD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Åsberg Depression Rating Scale (MADRS) Pre-Post Change | For patients with TRD, the MADRS will be administered. The MADRS contains 10 items, and each item is scored 0-6. These item scores are summed to create a scale score; thus, scale scores range from 0 to 60. A scale score of 0 indicates the absence of depressive symptoms, while a score of 60 indicates severe depression. The primary outcome is the mean change in total MADRS score. A decrease in the mean MADRS score indicates a decrease (or improvement) in depressive symptoms, whereas an increase in the mean MADRS score indicates an increase (or worsening) in depressive symptoms. | Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later). | 
| Yale-Brown Obsessive Compulsive Scale | For patients with OCD, the YBOCS will be administered. Questions on the YBOCS examine the amount of time spent thinking and acting on obsessions and compulsions, how much impairment or distress is caused, and how much resistance and control the participant has over their thoughts or behavior. | Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression/Severity (CGI) Pre-Post Change | The CGI is a clinician-measured scale of 3 items: Severity of Illness (item 1), Global Improvement (item 2), and Efficacy Index (item 3). Items 1 and 2 are rated on a 7-point Likert scale (1=normal, 7=among the most extremely ill patients) with a possible response of not assessed. Item 3 is rated on a 4-point Likert scale from none to outweighs therapeutic effect. Items 1 and 3 are assessed in relation to last clinical encounter (if possible). | Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later). | 
| Generalized Anxiety Disorder, 7-item (GAD-7) Pre-Post Change | The GAD-7 is the self-reported anxiety questionnaire which scores each of the 7 symptoms of Generalized Anxiety Disorder in the last two weeks on a 4-point scale, i.e. 0 (not at all), 1 (several days), 2 (over half the days) and 3 (nearly every day). Functional impairment is also assessed from Not difficult at all to Extremely difficult. | Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later). | 
| Montreal Cognitive Assessment (MoCA) Pre-Post Change | The MoCA is a 30-point screening instrument for detecting cognitive dysfunction. It is used to assess the following cognitive domains: visuospatial/executive, naming, memory, attention, language, abstraction, delayed (short-term memory recall), and orientation. | Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later). | 
| Patient Health Questionnaire, 9-item (PHQ-9) Pre-Post Change | The PHQ-9 is the self-reported depression module of the PHQ, which scores each of the 9 symptoms of a major depressive episode on a 4-point scale, i.e. 0 (not at all), 1 (several days), 2 (more than half the days) and 3 (nearly every day). Functional impairment is also assessed from Not difficult at all to Extremely difficult. | Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later). | 
| Temperament and Character Inventory (TCI) Pre-Post Change | The TCI is a 240-item questionnaire. It operates with seven dimensions of personality traits, i.e. four so-called temperaments: Novelty Seeking (NS), Harm Avoidance (HA), Reward Dependence (RD), and Persistence (PS), and three so-called characters: Self-Directedness (SD), Cooperativeness (CO) and Self-Transcendence (ST). Each of these traits has a varying number of subscales. | Pre-assessment will be obtained within approximately 1 week of starting treatment. Post-assessment will be obtained as close as possible following completion of treatment course (usually 4-6 weeks later). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Electroconvulsive Therapy, Ketamine, Esketamine, Transcranial Magnetic Stimulation