Active clinical trials for "Depressive Disorder, Major"

This is a 52-week open-label extension (OLE) study that will evaluate the safety, tolerability, and effectiveness of NMRA-335140 in participants with major depressive disorder (MDD). Participants who completed a parent study investigating the efficacy of NMRA-335140 as a treatment for MDD (ie, NMRA-335140-301, NMRA-335140-302, or NMRA-335140-303), who provide informed consent, and who have no evidence of safety concerns that would preclude treatment with NMRA-335140 may be enrolled into this extension study.

To explore the effectiveness and safety of rTMS intervention with different targets in the left prefrontal cortex defined using the pBFS method, in adult patients with moderate and severe depressive disorder. Second, investigate the neural circuit that responds to the rTMS intervention using individualized brain image analysis, which may help to establish an effective target for the neuromodulation of patients with major depressive disorder.

The investigators propose a randomized 3-arm double-blinded parallel experimental trial (20 sessions over 4 weeks) in 75 patients with TRD. The three arms include (1) the combination of a fully individualized form of iTBS (using BOTH the frequency and E-field targeting approaches) (Ind-iTBS)), (2) iTBS individualized using E-field targeting only (targeted-iTBS) and (3) Standard iTBS treatment (i.e., typical iTBS localized to the DLPFC using the Beam F3 method). EEG data will be collected at rest and during a working memory task, at baseline, and at the end of treatment along with clinical assessments of depression severity. The target engagement dependent variable of interest in these three arms will be fronto-parietal theta connectivity measured through resting-state EEG. The investigators hypothesize that stimulation with Ind-iTBS will lead to greater changes in fronto-parietal theta connectivity than that produced with targeted-TBS and standard iTBS. Aim: To evaluate the effects of two individualized forms of iTBS (i.e., using BOTH the frequency and E-field individualization; Ind-iTBS) compared to iTBS individualized for E-field targeting only (targeted-iTBS) and standard iTBS on fronto-parietal theta connectivity. Hypotheses: (1) Ind-iTBS will lead to greater changes in fronto-parietal theta connectivity compared to both targeted-iTBS and standard iTBS. (2) Ind-iTBS will also lead to a greater reduction in depressive symptoms (as defined by the mean reduction in Montgomery Åsberg Depression Rating Scale Scores (MADRS)) compared to both targeted-iTBS and standard iTBS.

In the treatment of Major Depressive Disorder (MDD), total sleep deprivation 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 sleep deprivation has been suggested to increase synaptic strength. Although determining how sleep deprivation 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 sleep deprivation. In this project, the investigators will utilize a novel measure of glutamate imaging, GluCEST, to assess changes in glutamatergic activity, in addition to using a proxy measure, waking EEG theta activity, to assess synaptic strength following total sleep deprivation. Ten individuals (aged 25-50) with a DSM-V diagnosis of MDD will undergo baseline GluCEST imaging and waking EEG prior to and following approximately 30 hours of total sleep deprivation. Both clinician-administered and subjective mood measures will be collected. It is predicted that sleep deprivation 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.

Background of the study: Major depressive disorder is a severe neuropsychiatric condition that affects approximately 15% to 18% of people worldwide during their lifetime (Malhi & Mann, 2018). Selection of the optimal treatment is difficult. A certain correlation (functional / structural, vascular or a mix of both) is expected between clinical data (obtained from psychometric tests such as the HDRS and psychiatric evaluations) and MRI parameters (functional activity, structural connectivity, anatomical variations, perfusion / diffusion etc.). Objective of the study: Identification of MRI-based biomarkers to predict clinical outcome of major depressive disorder in comparison with healthy controls. Outcome is defined by level of depressive and cognitive symptomatology and related comorbidity. Study design: An independent treating physician will inform a potentially eligible patient and ask whether he/she is interested in voluntary participation in the study. If he/she is interested, the independent treating physician will refer the patient to one of the clinicians from the GGz who is also involved in the Neurotrend study for further steps such as providing the information letter / informed consent and scheduling an intake interview at least one week after receiving all necessary information. Healthy controls will be recruited through public advertisement and via the website www.neurotrend.nl. Pilot subjects will be recruited from the Eindhoven University community and via the website www.neurotrend.nl. Both groups, healthy controls and pilot subjects, will have at least one week to consider and decide on participation. One week later an intake session will take place in which the inclusion and exclusion criteria will be checked. During this session, patients can also ask questions about the study and the informed consent will be signed if the participant is willing to participate voluntarily in the study. Subsequently at the end of the intake session, a starting (baseline) date will be planned for this participant . The actual participation starts at baseline. In total, 120 depressed patients and 60 healthy controls will participate in the study. Each participant visits Kempenhaeghe twice, whereby each session, is dedicated to complete questionnaires and cognitive tests, such as memory tasks and eye tracking. In the last hour, the participant will be scanned (MRI). Two weeks before each visit, the participant has to fill in some questionnaires that have been sent to the participant. Study population: 120 patients with major depressive disorder and 60 healthy controls*. * Inclusion of up to 30 healthy "pilot" participants for technical evaluation. See above. Primary study parameters/outcome of the study: Hamilton Depression Rating Scale (HDRS) scores Treatment / medication usage MRI metrics (varies per MRI modality, an example is volume per region for a T1-weighted scan and fractional anisotropy for diffusion-weighted scans). Secondary study parameters/outcome of the study (if applicable): Scores of psychometric assessments (e.g. STAI-DY1 - anxiety score) Scores of cognitive assessments (e.g. average response time for the eye-tracking task) Nature and extent of the burden and risks associated with participation, benefit and group relatedness (if applicable): The participant burden is low and is divided into an intake session and two research sessions. The MRI scan is non-invasive, and subjects can indicate that they want to stop the scan at any time during the scan by squeezing a type of balloon that will lie next to the subject in the case that they feel uncomfortable or for any other reason. Subjects with MRI contraindications (e.g. claustrophobia, pregnancy or implants not suitable for MRI) are already excluded in advance and will therefore not participate in the study at all. Mostly, the subjects will lie still during the scan, except for one affective task in which they will be asked to match different emotional faces for about 5 minutes.The cognitive tests will only consist of memory, reaction speed, attention, and processing speed tasks which in total, do not last more than 30 minutes. The risks of the MRI scanner (CE-marked) are minimal.

Investigators are conducting this double-blind, randomized control trial (RCT), to compare inhaled N2O+ treatment as usual (TAU) versus inhaled placebo+TAU; demonstrating the feasibility and tolerability of the intervention in an emergency department (ED) setting on an acutely suicidal population.

This study aims at developing an online system for the remote delivery of EMDR therapy in Pakistan. Moreover, this study will compare the efficacy of online EMDR therapy with face-to-face EMDR therapy.

Background: The prevalence of depressive disorder, particularly major depressive disorder is on the rise globally and the use of antidepressant medication for treatment does not usually resulting in full remission. However, combination of antidepressant medication and psychotherapy for treatment of major depressive disorder (MDD) increase the rate of full remission compared to antidepressant monotherapy. This three-armed, parallel-group, double-blind, randomized control trial (RCT) aims to assess and compare the effects of combination of exergame and acceptance and commitment (e-ACT) training programme and ACT only on psychiatric symptoms (depression and anxiety), experiential avoidance (EA), quality of life (QoL), and biomarkers of depression (such as BDNF, TNF-α, IL-6, IL-1β, CRP, and VEGF) among MDD patients. Methods: This RCT will recruit 120 patients diagnosed with MDD who will be randomized using stratified permuted block randomization into three groups, which are combined e-ACT training programme, ACT only and treatment-as-usual control groups in a 1:1:1 allocation ratio. The participants in the e-ACT and ACT only intervention groups will undergo once a week intervention sessions for 8 weeks. Assessments will be carried out through three time points, such as the first assessment before intervention began (t0), second assessment immediately after completion of intervention at 8 weeks (t1) and third assessment 24 weeks after completion of intervention (t2). During each assessment, the primary outcome assessed is the severity of depression symptoms, while the secondary outcomes assessed are severity of anxiety symptoms, QoL, EA, and biomarkers of depression.

The investigators aim to investigate whether the intervention effect of pBFS-guided rTMS therapy targeting DLPFC is superior to the intervention effect of the traditional "5 cm-rule" guided rTMS therapy in patients with depressive disorders.

The aims of this study are to: Determine the proportion of participants who are underdosed or overdosed under recommended dosing regimen of escitalopram for the depression treatment (10 mg/day) Determine and quantify clinical benefits of personalized escitalopram dosing regimen based on the escitalopram blood level monitoring Retrospectively estimate whether the information on CYP2C19 genotype is useful in the prediction of escitalopram blood level.