Major Depressive Disorder (MDD)

The goal of this clinical trial is to learn if DT-101 can treat depression in adults. The effect of DT-101 will be compared to placebo. Subjects will attend the clinic every couple of weeks complete general health checks and complete questionnaires.

In the treatment of Major Depressive Disorder (MDD), ketamine can produce rapid but short-lasting improvements in mood. In order to develop a new generation of treatments with rapid and sustained efficacy, a better understanding of the mechanism of action is urgently needed. One candidate mechanism is the modulation of synaptic strength mediated by glutamatergic activity as ketamine has been suggested to increase synaptic strength. Although determining how ketamine impacts the glutamatergic system is essential to isolating its mechanism of action, the invasive nature of most assessment methods has limited our ability to do so in humans. The proposed research aims to determine if changes in glutamatergic activity, reflecting the modulation of synaptic strength, underlie the antidepressant effects of ketamine. In this project, the investigators will utilize a novel measure of glutamate imaging, GluCEST, to assess changes in glutamatergic activity to assess synaptic strength following ketamine administration. Ten individuals (aged 25-65) with a DSM-V diagnosis of MDD will undergo baseline GluCEST imaging prior to and following ketamine infusion. Both clinician-administered and subjective mood measures will be collected. It is predicted that ketamine will improve mood and increase glutamatergic activity and synaptic strength. Results from this project have the potential to identify the modifiable mechanisms by which rapid antidepressants work which could ultimately stimulate the development of novel interventions that work through the modulation of glutamatergic activity.

Depression is a common mental health problem affecting almost 300 million people worldwide. Antidepressants are recommended as one of the first line treatments for people with moderate-to-severe symptoms of depression. In our recent trial, PETRUSHKA, on the acute treatment of depression, we demonstrated that the PETRUSHKA Tool, an evidence-based shared decision support system to personalise antidepressant treatment, in comparison with usual care reduced by almost 40% the number of participants stopping their antidepressant early, also improving their depression and anxiety symptoms. To identify the best treatment for each individual, the PETRUSHKA Tool used clinical and demographic predictors. Pilot data show that genetic information can aid stratification of people experiencing depression and better target their treatment. Genetic data can be collected using low-cost DNA-sequencing technology in diverse clinical settings and low-resource environments. Hence, we hypothesised that individual-level pharmacogenomic information can further personalise antidepressant treatment. In this project called PRADA ("Prescribing the Right Agent for Depression in Adults"), we will develop and test in a global trial across Ethiopia, Pakistan and the UK, an evidence-based multimodal web-tool to help participants and clinicians choose the best pharmacological treatment for depression jointly, based on participant preferences and their individual clinical, demographic, cultural, and also genetic profile (PRADA Tool). We will compare the new tool with the PETRUSHKA Tool in a blind fashion, measuring adherence to antidepressant treatment, clinical response and quality of life over a 12-month follow-up.

This multi-center, double-blind study, randomized controlled trial aims to evaluate the efficacy and safety of Temporal Interference transcranial Alternating Current Stimulation (TI-tACS) in patients with major depressive disorder (MDD) Participants with major depressive disorder will be randomized to receive high-frequency TI-tACS(130 Hz), low-frequency TI-tACS(2Hz), or sham stimulation targeting the right amygdala. The intervention consists of 20 stimulation sessions administered over 2 weeks (twice a day for 5 consecutive days, followed by a 2-day break, and another 5 consecutive days). Clinical assessments will be conducted at baseline, during treatment, and at multiple follow-up time points up to 6 months. The primary outcome for MDD is the change from baseline in the Hamilton Depression Rating Scale (HAMD-17) at week 2. Secondary outcomes include changes in clinical symptoms, cognitive function, and safety profiles.

This is a randomized, parallel-group, double-blind, placebo-controlled, monotherapy study to evaluate the efficacy, safety, and tolerability of SPT-300 (GlyphAllo) in adults with major depressive disorder (MDD), with or without anxious distress.

The purpose of this study is to determine the efficacy, safety and tolerability of CYB003 compared to matching placebo as adjunctive treatment in patients with MDD. For more information about the EMBRACE study, including participating study locations, and to register your interest in learning more about participation, please visit the study website: https://embrace-mdd-trial.com/

The purpose of this research is to see if an experimental treatment for depression called intermittent theta burst stimulation (iTBS), a form of transcranial magnetic stimulation (TMS) can be improved for better results using electroencephalography (EEG) recordings (brain waves) for individuals with Major Depressive Disorder (MDD). This is a feasibility study to test a "closed-loop" procedure which guides the timing of this FDA-cleared form of TMS. Each participant will receive an active experimental treatment, and the timing of the TMS pulses will be at one of three phases in the brain wave of interest.

The goal of this clinical trial is to learn whether brief psychoanalytic therapy and cognitive behavioral therapy (CBT) reduce depressive symptoms in adults aged 18 to 65 who have been diagnosed with major depressive disorder. The main questions it aims to answer are: * Does brief psychoanalytic therapy reduce depression severity more than a waitlist control condition after 18 weeks? * Does CBT reduce depression severity more than a waitlist control condition after 18 weeks? Researchers will also compare brief psychoanalytic therapy with CBT to explore whether one works better than the other, and will examine whether changes in defense mechanisms and automatic negative thoughts explain improvement in each therapy. Participants will: * Be randomly assigned to brief psychoanalytic therapy, CBT, or a waitlist control group (30 participants per group) * In the therapy groups, attend 18 weekly individual therapy sessions of 50 minutes each * In the waitlist group, continue their usual psychiatric care without psychotherapy for 18 weeks, and then be offered one of the therapies * Complete clinical interviews and questionnaires about depression, anxiety, quality of life, thought patterns and coping styles before treatment, at week 9 and at week 18 * In the therapy groups, complete follow-up assessments 6 and 12 months after treatment ends

The goal of this clinical trial is to learn if ACP-211 can help treat adults with major depressive disorder (MDD) who have not improved with antidepressant therapy (ADT), including those with treatment resistant depression (TRD). The main questions the study aims to answer are: * Does ACP-211 work better than a placebo (a look-alike capsule with no medicine) to reduce symptoms of depression? * What adverse events do participants have when taking ACP-211?

The goal of this study is to collect feasibility data on combining structured exercise aimed to improve physical fitness, and intermittent TBS (iTBS) in treating individuals diagnosed with difficult-to-treat depression who are physically inactive. By conducting this trial, we will compare the therapeutic benefits of the combined approach against the standard treatment of iTBS alone (without exercise). These findings will be used to inform future large-scale projects in which we will investigate, in a larger sample size, whether structured exercise aimed to improve fitness as recommended by most public exercise guidelines (i.e., ≥3x/week, moderate-to-vigorous intensity) serves as an active ingredient that amplifies the effectiveness of iTBS. Ultimately, the insights gained from this study will be valuable for clinicians seeking to alleviate depressive symptoms in MDD through neuromodulation techniques such as iTBS.

This prospective observational study aims to evaluate changes in psychological defense mechanisms in patients with non-psychotic major depressive disorder (MDD) undergoing repetitive Transcranial Magnetic Stimulation (rTMS) therapy. The study investigates whether rTMS induces a shift from immature to more mature defense mechanisms and assesses how these changes relate to improvements in depressive symptom severity, anxiety levels, and overall functionality at baseline, 1-month, and 3-month follow-ups.

Major Depressive Disorder (MDD) significantly impacts quality of life and health status. Standard treatments include medical, psychological, and pharmacological approaches, with physical therapy often playing a less central role. This pilot study aims to investigate the potential benefits of incorporating a physical therapy program, based on therapeutic exercise and health education, within the management of MDD in a short-stay psychiatric unit. This project will implement a physical therapy intervention consisting of twice-weekly sessions of active joint mobility exercises, strength training (body weight/elastic bands), balance exercises, and progressive muscle relaxation, integrated with health education on the benefits of physical activity for mental health and strategies for long-term adherence. Adult patients (over 18 years) diagnosed with MDD, admitted to the short-stay psychiatry unit of Royo Villanova Hospital in Zaragoza and under regular medical, psychological, and pharmacological treatment, will be recruited for this study. All participants will receive the physical therapy program in addition to their standard care. The main objective is to analyze the preliminary efficacy of a physical therapy intervention program based on health education and therapeutic exercise in improving quality of life and health status in adults with MDD during their stay in a short-stay psychiatric unit. A secondary objective is to explore the perceptions of these patients and the healthcare professionals regarding the implementation of this multimodal treatment approach, including barriers and facilitators encountered. Hypothesis: A physical therapy program integrating therapeutic exercise and health education is feasible and preliminarily effective in improving quality of life and health status in adults with MDD in a short-stay psychiatric unit and is perceived positively by both patients and healthcare professionals regarding its implementation.

The purpose of this study is to determine the efficacy and safety of milsaperidone compared to placebo as adjunctive therapy in patients with Major Depressive Disorder

The goal of this clinical trial is to learn if the anti-inflammatory medication adalimumab improves depressive symptoms in adults with Major Depressive Disorder (MDD) who are already taking the anti-depressant medication Lexapro (escitalopram). The main questions it aims to answer are: 1. Does adalimumab improve the symptoms of some patients with MDD who are already taking an anti-depressant? 2. What characteristics predict for whom adalimumab has anti-depressant properties. Researchers will compare adalimumab to a placebo (a look-alike substance that contains no drug) to see if adalimumab works to improve depressive symptoms as an add-on drug to the anti-depressant Lexapro (escitalopram). For these primary aims the participants will: 1. Visit the clinic once every 2 weeks for a checkups and injection of adalimumab or placebo from the study psychiatrist (Day 1, 15, 29, and 43 for injections) 2. Complete short (\<5 min) daily surveys for the 57 day duration of the study.

The goal of this clinical trial is to learn if a drug called TNX-102 SL works to treat moderate to severe major depressive disorder in adults. It will also learn about the safety of TNX-102 SL. The main questions it aims to answer are: Does TNX-102 SL improve depression symptoms according to a depression symptom rating scale? What medical problems do participants have when taking TNX-102 SL? Researchers will compare TNX-102 SL to a placebo (a look-alike substance that contains no drug) to see if TNX-102 SL works to treat major depressive disorder. Participants will: Take TNX-102 SL or a placebo every night at bedtime for 6 weeks Visit the clinic once every 2 weeks for checkups and tests

The goal of this clinical trial is to learn if combining a ketogenic diet with a personalized, accelerated brain stimulation treatment (iTBS) works better than iTBS with a standard healthy diet to reduce depression symptoms in adults with treatment-resistant depression. The main questions it aims to answer are: * Does iTBS combined with a ketogenic diet improve depression symptoms more than iTBS combined with a standard healthy diet? * Does the ketogenic diet change ketone levels over time? * Is it safe, tolerable, and feasible to follow a ketogenic diet during accelerated iTBS treatment? We will compare a ketogenic diet to a Canadian Food Guide-aligned diet, both combined with iTBS, measuring depression severity using standard clinician-rated and self-report scales. Participants will: * Follow either a ketogenic diet or a standard healthy diet for 12 weeks, starting with a 3-week lead-in period before iTBS begins * Undergo a course of personalized, imaging-guided accelerated iTBS while continuing their assigned diet * Complete clinical and cognitive assessments, blood tests, and brain MRI scans before and after treatment * Have their ketone levels checked regularly throughout the 12-week period

This randomized, double-blind, sham-controlled, parallel-group clinical trial will evaluate the efficacy and safety of individualized functional connectivity-guided accelerated intermittent theta-burst stimulation (iTBS) in adults with major depressive disorder (MDD). A total of 90 participants will be randomly assigned in a 1:1 ratio to receive either active iTBS or matched sham stimulation. Treatment will be administered over 5 consecutive days, with 10 stimulation sessions per day. For each participant, an individualized stimulation target within the left dorsolateral prefrontal cortex will be identified using resting-state functional magnetic resonance imaging (MRI). The primary objective is to compare the change in depressive symptoms, measured by the Montgomery-Åsberg Depression Rating Scale (MADRS), from pre-treatment baseline (Day -1) to 4 weeks post-treatment (Week 4; Day 34) between the active and sham groups. Changes in other clinical symptoms, treatment response, remission, and safety will also be assessed during follow-up through 8 weeks after treatment. Multimodal MRI, resting-state electroencephalography (EEG), and transcranial magnetic stimulation combined with EEG (TMS-EEG) will be collected at prespecified time points. These measures will be used to explore treatment-related changes in brain function and connectivity and to identify potential neuroimaging and neurophysiological biomarkers associated with clinical improvement and the maintenance of treatment effects.

This study will compare transcranial magnetic stimulation (TMS) with sham TMS in people with opioid use disorder who are taking buprenorphine and have major depressive disorder with ongoing depressive symptoms. The study will evaluate whether TMS improves depressive symptoms and reduces opioid craving. The study will also assess smoking behaviors, treatment acceptability, and any side effects related to TMS.

This study aims to evaluate the clinical efficacy and neurophysiological mechanisms of home-based spaced tDCS in TRD through a randomized, double-blind, sham-controlled trial conducted under remote supervision. Specifically, this trial will: (1) compare the efficacy of active versus sham spaced tDCS on depressive symptom severity in individuals with TRD and (2) characterize neurophysiological changes associated with spaced tDCS using TMS-EEG, TMS-EMG and resting state EEG.

The goal of this pilot clinical trial is to learn if a faster brain stimulation schedule is practical, safe, tolerable, and acceptable. This study looks at accelerated intermittent theta burst stimulation, or accelerated iTBS. This is a non-invasive type of magnetic brain stimulation. This study is for adults with post-traumatic stress disorder (PTSD) and major depressive disorder (MDD). The main questions this study aims to answer are: 1. Can participants complete six short brain stimulation sessions per day for five days? 2. Is this treatment schedule safe and tolerable for participants? 3. What changes occur in depression symptoms, PTSD symptoms, anxiety, quality of life, and brain activity over time? Participants will: 1. Complete health screening and baseline assessments. 2. Receive six short sessions of magnetic brain stimulation per day for five days. 3. Have their brain activity measured using an EEG recording. 4. Return for a post-treatment assessment at Week 2 and follow-up visits at Week 5 and Week 12.

Transcranial magnetic stimulation(TMS) is a non-invasive form of brain stimulation that is cleared by the United States Food and Drug Administration (FDA) for depression. Conventional TMS involves daily weekday treatments for 6-8 weeks. These treatments are targeted using each person's scalp measurements. With conventional TMS, approximately 50-55% of people show a 50% or more improvement in depressive symptoms (in other words, they "respond" to treatment). Studies are trying to make TMS work better and faster. A new form of TMS called accelerated TMS (aTMS) involves mutliple treatments a day. One specific aTMS protocol involves 10 treatments per day for 5 days. These treatments are targeted using each person's brain scan (magentic resonance imaging, MRI). With this specific aTMS protocol, approximately 70-90% of people show a 50% or more imporvement in depressive symptoms. While these results are exciting, scientists are not sure why this specific aTMS protocol works better than conventional TMS. It could be the dose and schedule of treatment, or it could be the MRI-based targeting. Answering this question is important because MRI-based targeting is expensive and difficult to do in many settings. This study aims to determine if MRI-based targeting is better than scalp-based targeting for aTMS for depression. In this study, everyone who enrolls and meets criteria will be randomly assigned to MRI- versus scalp-based aTMS targeting.

This randomized, sham-controlled clinical trial aims to evaluate the efficacy and safety of amygdala-targeted transcranial temporal interference stimulation (tTIS) in adults with major depressive disorder (MDD) and to explore its potential neurobiological mechanisms. The main questions this study aims to answer are: Whether active amygdala-targeted tTIS reduces depressive symptoms compared with sham stimulation. Whether tTIS produces changes in amygdala-related neural activity and functional brain networks that are associated with clinical improvement. Participants will be randomly assigned to receive either active tTIS or sham stimulation. They will complete a course of stimulation sessions and undergo clinical assessments before and after the intervention. Neuroimaging assessments will also be performed to investigate treatment-related changes in the amygdala and associated brain networks.

This Phase 3, multicenter, randomized, double-blind, placebo-controlled clinical trial is designed to evaluate the efficacy and safety of lurasidone as adjunctive therapy in adult patients with major depressive disorder (MDD) who show an inadequate response to antidepressant monotherapy. Eligible participants will continue their background antidepressant treatment and be randomized to receive either lurasidone (20, 40, or 60 mg/day) or placebo for 8 weeks. The primary endpoint is the change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Week 8. Secondary endpoints include response and remission rates, changes in Clinical Global Impression-Severity (CGI-S), 17-item Hamilton Depression Rating Scale (HAM-D17), Hamilton Anxiety Rating Scale (HAM-A), and Sheehan Disability Scale (SDS) scores. Safety assessments will include adverse events, laboratory tests, electrocardiograms (ECGs), vital signs, and suicidality monitoring Columbia-Suicide Severity Rating Scale (C-SSRS).

This study seeks to examine the effects of treatment with a selective serotonin reuptake inhibitor (SSRI), escitalopram, a first-line treatment for depression, in combination with placebo or with extended-release memantine, on neuropsychological function, regional brain activity assessed by functional magnetic resonance imaging, and depressive symptoms, in participants with Major Depressive Disorder. Escitalopram is administered in an open-label fashion in this study; extended release memantine is administered in a double-blind, randomized, placebo-controlled manner.

The goal of this clinical trial is to understand how patient education surrounding a one-time, consciousness-altering medical intervention impacts the antidepressant response to the intervention in adults with major depressive disorder. In this study, the consciousness-altering medical intervention is a single infusion of propofol, an intravenous anesthetic which might have antidepressant properties. The main question this study aims to answer is: Does the focus of patient education influence the antidepressant response to a single intravenous infusion of propofol? Researchers will compare response-focused vs. diagnosis-focused education. Qualifying participants will: * Undergo a single intravenous infusion of propofol which will induce a temporary state of sedation * Wear an EEG cap that records brain activity during sedation * Be randomized to receive either response-focused or diagnosis-focused education about their brain signals after they recover from sedation * Be asked to fill out surveys about their mood and other measures of well-being before and after treatment