Clinical Research Directory

Signature Response to Light Therapy in Unipolar and Bipolar Major Depressive Episode (MDE)

Major depressive episode (MDE) are severe and common psychiatric disorders that affect up to 20% of the general population. MDE cause a decrease in psychosocial functioning, quality of life, and is associated with a high rate of suicides. They will be the leading cause of disability by 2030 according to the World Health Organization. The international effort carried out to identify biomarkers of MDE has been hampered by the heterogenous nature of MDE (unipolar, bipolar, seasonal, non-seasonal) and their heterogeneous response to treatment. Response rate to antidepressant drugs is only 40 to 50%, leading to the use of drug combinations and development of alternative therapeutics such as light therapy (LT). It was demonstrated that LT, as a first line treatment of MDE with and without seasonal pattern (± SP), has comparable efficacy to antidepressants. LT has the advantage of being also effective in improving both sleep, alertness and circadian rhythms, which may be altered in depression, contrary to antidepressant drugs that target mainly mood. Further research is warranted to determine the most efficient lighting parameters to use depending on depression characteristics, as well as to identify signature biomarkers of response. Besides, no studies have directly evaluated both subjective and objective biomarkers of sleep, wake, biological rhythms, and light signalling pathways and activation in patients with MDE ± SP. The main objective of the research will be to identify the signature of response to LT examining the correlation between the measures of biological and clinical parameters before LT and their evolution at the end of the procedure, and the therapeutic response. The primary endpoint of the study will be the therapeutic response to LT measured by the difference of MADRS score between Visit 1 and Visit 4 (end of the therapeutic protocol). Therapeutic response to LT considered as a success will be defined as at least a 50% reduction of MADRS score between the two visits.

University of Iowa Interventional Psychiatry Service Patient Registry

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").

Lithium Effects on the Brain's Functional and Structural Connectome in the Treatment of Bipolar Disorder

Lithium is highly effective in the treatment of bipolar disorder. This study aims to investigate, for the first time, the impact of lithium monotherapy on the structural and functional connectivity of the brain using MRI imaging.

Presynaptic Imaging in Major Depressive Episodes After COVID-19

The goal of this observational study focuses on understanding and addressing a subset of persistent neuropsychiatric symptoms occurring within 3 months after mild to moderate COVID-19 infection (COVID-DNP). COVID-DNP encompasses major depressive episodes (MDE) with or without additional neuropsychiatric symptoms.

Personalized Ultrasonic Brain Stimulation for Depression (R61)

This study will evaluate a new form of non-invasive brain stimulation for individuals with depression. Personalized low-intensity transcranial focused ultrasound stimulation will be delivered using a range of stimulation parameters during psychological and physiological monitoring. Individualized optimal targets will be selected using structural MRI and diffusion tractography. Brain target engagement will be evaluated using functional MRI.

At-Home tDCS as Maintenance Therapy

The primary purpuse of this pilot study is to find out whether a home-based transcranial direct current stimulation (tDCS) program is feasible and well tolerated as maintenance therapy and whether there are early signs that it helps maintain the clinical clinical benefits achieved during successful acute inpatient treatment. Participant population: Adults (18+) with depressive disorder who had already improved/stabilized after acute treatment at our clinic (esketamine, repetitive transcranial magnetic stimulation , or electroconvulsive therapy). Main questions: Feasibility: Do participants reliably complete the home program and stay in the study? Preliminary effectiveness: Do improvements of depressive symptoms hold up over the 4-week treatment and 2-week follow-up (based on self-report and clinician-rated scales)? Participants receive standardized instruction from trained staff and a portable tDCS device (with cap and small sponge electrodes) and complete 20 home sessions over 4 weeks (5 per week), each 30 minutes at a very low current (2 mA); the device gently ramps current up/down for comfort. During treatment, participants use a smartphone app with step-by-step guidance and reminders; sessions are automatically logged. They will also fill out short weekly self-rating questionnaires and join brief phone check-ins every 2 weeks. Where: Department and Outpatient Clinic of Psychiatry and Psychotherapy, Klinikum rechts der Isar, Technical University of Munich Safety \& data privacy: The device monitors electrode contact and pauses automatically if contact is poor. Typical sensations can include mild tingling or redness. The app stores anonymized session data so the care team can track progress; no personal data are exchanged between the app and the stimulator, and access is via a secure clinical portal.

Early Effects of Ketamine vs Placebo With Venlafaxine in Severe Depression Patients

Unipolar major depressive disorder is the leading cause of disability worldwide. The most commonly used treatments for major depressive episodes (MDE) are antidepressant medications. However, they have limited efficacy and their onset of action is long, ranging between 2 to 6 weeks. During this period, hospitalization can become necessary, especially for severe MDE. It is crucial to improve the early effectiveness of treatments for these patients in order to alleviate their suffering, limit complications (suicidal risk), and reduce hospitalization durations (approximately 1000 euros per day). The efficacy of intravenous ketamine has been demonstrated in pharmaco-resistant depression but remains to be proven in non-pharmaco-resistant severe MDE. Additionally, PET imaging using \[11C\]UCB-J, which allows the in vivo study of synaptic density in the human brain, has shown significant decreases in synaptic density in unipolar patients with severe MDE. Furthermore, a single ketamine infusion was found to enhance synaptogenesis

The Impact of Coach-guided Risk Communication on the Risk of Major Depression

Depression is a highly prevalent and disabling mental health problem. One way of preventing depression is to stop it before it happens through effective self-management. Working with potential users, a coach-guided, personalized depression risk communication tool (PDRC) was developed for sharing information about individualized depression risk, risk profile (risk factors present), potential risk reduction and evidence-based self-help strategies. It is anticipate that the PDRC will greatly motivate users to actively engage in self-help and help seeking, leading to a reduced risk of depression. The proposed study will recruit 500 male and 500 female adults who are at high risk of having depression across Canada, and randomly allocate them into the intervention and control groups. Participants will be followed for 12 months. The data of the trial will allow us to answer the questions: (1) Can the coach-guided PDRC reduce the risk of depression? (2) Does the intervention motivate people to actively engage in evidence-based self-help and help-seeking behaviors? (3) For whom the intervention works best? and (4) what are the costs and potential savings associated with the intervention? If successful, this project will offer a novel and effective tool for early prevention of major depression in the Canadian general population, help us understand how it works and the cost-effectiveness of implementing such a tool in the community from the economic perspective.

Feasibility of Home-Based Intermittent 60Hz Light Therapy for Major Depressive Disorder (MDD)

This pilot study evaluates the feasibility, safety, and preliminary efficacy of home-based 60Hz intermittent light therapy in adults with a major depressive episode (MDE). Participants will be randomized in a 2:1 ratio to receive either active or sham 60Hz intermittent light stimulation for 30 minutes daily (Monday through Friday) over three weeks. The light is delivered through a wearable headset. Clinical assessments will be conducted remotely at baseline, mid-point, post-treatment, and follow-up to measure changes in depressive symptoms.

Add-on Buprenorphine at Analgesic Doses for the Treatment of Severe Suicidal Ideas During a Major Depressive Episode

This study aims at investigating if adjunctive buprenorphine at low dose to treatment as usual is effective in reducing severe suicidal ideas in major depressive episode, and at determining the most effective dose.

Metabolomics During ElectroConvulsivoTherapy

Investigators will measure the variation of blood Metabolome through 1H NMR at several time points during the course of electroconvulsivetherapy in patients with a major depressive episode. Patients with a major depressive disorder or a bipolar disorder and a current major depressive episode will be included in this study. Investigators hypothesized that Metabolome could be a source to predict response during ECT and to help understanding underlying biological mechanisms.

Circuit-Based Approach to Suicide: Biomarkers, Predictors, and Novel Therapeutics

This neuroimaging study is a clinical trial investigating the effectiveness of intermittent theta-burst transcranial magnetic stimulation (iTBS-TMS) to the inferior parietal lobule (IPL) in reducing suicide risk in patients with major depressive episode (MDE) or borderline personality disorder (BPD).

Patient-oriented Randomized Pragmatic Feasibility Trial with RTMS in Depression and Anxiety

This trial compares intermittent theta-burst stimulation (iTBS) to low frequency repetitive transcranial magnetic stimulation (LFR) in regards to depression and anxiety outcomes in 100 patients with treatment resistant depression (TRD).

Digital Interventions for Adults with Treatment-Resistant Depression: a Pilot Study

The goal of this observational study is to learn about remote mental health monitoring technology for adults with treatment-resistant depression. The main question it aims to answer is: are digital mental health monitoring tools (an electronic data capture platform and wearable device (e.g., smartwatch or smart-ring)) feasible to implement alongside clinical treatment for depression? The secondary aim of this study is to inform preliminary clinical parameters for larger, definitive studies. Participants receiving neuropsychiatric treatment (repetitive transcranial magnetic stimulation, intravenous ketamine, or electroconvulsive therapy) as part of their regular medical care for treatment-resistant depression in the Interventional Psychiatry Program will have their clinical assessment data entered into a digital platform and will wear an accessory-based wearable device for the duration of treatment.

Accelerated Intermittent Theta Burst in Treatment-Naive Adolescents

This is a single-site open-label clinical trial of the Stanford Accelerated Intermittent Neuromodulation Therapy (SAINT®) protocol. The goal of this clinical trial is to learn if a new form of transcranial magnetic stimulation (TMS)-known generally as accelerated intermittent theta burst stimulation (aiTBS) and specifically as SAINT®-is effective as a first-line therapy in treating adolescents aged 14-19 years-old in their first episode of depression who have not undergone a full course of depression treatment prior to starting the trial and who remain antidepressant-free throughout the trial. The main questions this trial aims to answer are: * Does SAINT® relieve symptoms of depression as a first-line therapy in adolescents? * Is SAINT® a feasible option as a first-line treatment for adolescent depression? Researchers will measure the depression symptoms in adolescent participants before and after SAINT®. Parents of the adolescent participant will also participate in the study providing information about their experience and preference for TMS as a first-line treatment. Adolescent participants will: * Remain antidepressant-free throughout the study period of 6-7 weeks. * Receive an MRI of their head for precision targeting * Receive 5 days of aiTBS (SAINT®)

Personalized Ultrasonic Brain Stimulation for Depression

This study will evaluate a new form of non-invasive brain stimulation for individuals with depression. Personalized low-intensity transcranial focused ultrasound stimulation will first be delivered using a range of stimulation parameters during psychological and physiological monitoring. A well-tolerated stimulation protocol will then be selected for subsequent testing in a blinded randomized sham-controlled cross-over trial to evaluate brain target engagement using magnetic resonance imaging.

Reward Processing and Depressive Subtypes: Identifying Neural Biotypes

Deficits in motivation and pleasure are common in depression, and thought to be caused by alterations in the ways in which the brain anticipates, evaluates, and adaptively uses reward-related information. However, reward processing is a complex, multi-circuit phenomenon, and the precise neural mechanisms that contribute to the absence or reduction of pleasure and motivation are not well understood. Variation in the clinical presentation of depression has long been a rule rather than an exception, including individual variation in symptoms, severity, and treatment response. This heterogeneity complicates understanding of depression and thwarts progress toward disease classification and treatment planning. Discovery of depression-specific biomarkers that account for neurobiological variation that presumably underlies distinct clinical manifestations is critical to this larger effort.

Cohort of Patients Suffering From Major Depressive Episode With Evaluation of Sleep, Circadian Rhythms and Psychiatric Disorders

Despite international efforts to identify biomarkers of depression, none has been transferred to clinical practice, neither for diagnosis, evolution, nor therapeutic response. This led us to build a French national cohort (through the clinical and research network named SoPsy within the French biological psychiatry society (AFPBN) and sleep society (SFRMS)), to better identify markers of sleep and biological rhythms and validate more homogeneous subgroups of patients, but also to specify the manifestations and pathogeneses of depressive disorders.

Comparing Uni- and Bi-lateral TBS in Major Depression

Repetitive transcranial magnetic stimulation (rTMS) is a Health Canada approved treatment for major depression. Theta burst stimulation (TBS) is a very promising new treatment for major depression that allows a 15-fold reduction in duration of daily sessions. However, no large scale naturalistic study has assessed the superiority of bilateral TBS in comparison with unilateral left TBS. In fact, no TBS study thus far has included both unipolar and bipolar depression, or other psychiatric comorbidities such as anxiety. Maintenance has yet to be studied with TBS, along with an effective maintenance protocol to prevent relapse. Our study aims to explore and address these gaps.