View clinical trials related to Major Depressive Disorder.
Filter by:Objective: Metabotropic glutamate receptors (mGluRs) are G-protein coupled receptors that respond to glutamate by activating proteins inside nerve cells that affect cell metabolism, thereby fine-tuning the signals sent between cells to maintain balance in neuronal activity. mGluR subtype 1 (mGluR1s) are located in several brain regions, including the cerebellum, hippocampus, olfactory bulb, and basal ganglia. mGluR1 activation stimulates phospholipase C, resulting in phosphoinositide hydrolysis and increased intracellular calcium levels. Successful development of a positron emission tomography (PET) ligand to image mGlurR1 would impact clinical management of brain disorders characterized by disruptions in glutamatergic transmission, including anxiety and stress disorders, drug addiction, epilepsy, Huntington s disease, and Parkinson s disease. However, detailed study of mGluR1s has heretofore been hindered by the lack of high affinity and selective ligands for this receptor subtype. The present protocol will evaluate the ability of a new PET ligand, [18F]FIMX, to image and quantify mGluR1 in the brain of healthy human volunteers. This protocol covers four phases: 1. Phase 0: screening whole-body scan; 2. Phase 1: kinetic brain imaging to quantify mGluR1 in brain relative to concurrent measurement of the parent radioligand in arterial plasma; 3. Phase 2: if the tracer is successful in Phase 1, we will estimate radiation-absorbed doses of [18F]FIMX by performing whole body imaging; 4. Phase 3: test-retest analysis of brain binding relative to concurrent measurement of the parent radioligand in arterial plasma. Study Population: Healthy adult female and male volunteers (n=22, ages 18 to 55) will undergo brain or whole-body imaging.. Design: This study will begin with a screening whole-body scan to confirm that the radioactivity has fairly broad distribution in several organs. For absolute quantification of mGluR1, 22 healthy controls will have brain PET imaging using [18F]FIMX and an arterial line. Up to 12 of them will have a test-retest scan. Eight additional subjects will have a whole body PET scan for dosimetry, which does not require an arterial line. <TAB> Outcome Measures To assess absolute quantitation of mGluR1 with [18F]FIMX, we will primarily use two outcome measures: the identifiability and time stability of distribution volume calculated with compartmental modeling. In test-retest study, we will calculate the retest variability. To assess whole-body biodistribution and dosimetry of [18F]FIMX we will use the organ time-activity curves....
This is a pilot study divided into two phases. IN phase 1 (completed) participants will be randomized to receive 8 weeks of Problem Solving Therapy (PST) alone or 8 weeks of a cognitive training game called, Evolution (Evo) plus clinical management. In Phase 2 (now recruiting), participants will be randomized to Evo, PST, and a different cognitive training program called Words. Words is similar to Evo in that it is an adaptive training program and includes case management. IN both studies participants will be assessed for clinical and functional magnetic resonance imaging (fMRI) outcomes at baseline, 4 weeks and 8 weeks.
This study will evaluate the efficacy and safety of ALKS 5461.
Major depression disorder (MDD) is a frequent and disabling mental disorder with great risk of recurrence and chronicity. Interpersonal factors are among the strongest predictors of the course and duration of an episode of depression. More specifically, social rejection is one of the most environmental risk factors of MDD. Targeted rejection predicts hastened onset of major depression. On the other hand, healthy subject show prosocial behavior after social rejection to reconnect to new source of social interaction. In addition to the potential impact of social exclusion on MDD onset, depressed patients may be more prone to be rejected as they encounter interpersonal difficulties and may less be able to reconnect to the social group after rejection. Recent neuroimaging data show that brain processing of social exclusion activate brain regions that are central to the pathophysiology of MDD. Some of these regions are also known to be activated during physical pain and may contribute to the aversive dimension of the experienced rejection. Pro-inflammatory cytokines are involved in MDD physiopathology and can induce social withdrawal behavior. Inflammation can modulate social interactions in mammals. Moreover, after a social stress such as social rejection, blood cytokines increase. At a cognitive level, self-esteem can modulate the sensitivity to social rejection. The major objective of the trial is to study sensitivity to social signals in MDD patient compared to healthy subject. The investigators hypothesize in MDD patient : (1) decrease of rapid facial reactions (RFR) to dynamic emotional faces expressing joy, (2) increase of RFR to dynamic emotional faces expressing sadness, (3) decrease of prosocial reaction after experimental social rejection. Secondary objective is to identify psychological and biological mediators We hypothetize in MDD patient: (1)mediating effect of systemic inflammatory cytokines, an (2) mediating effect of state self esteem 30 MDD patients and 60 healthy subject will be included. They will encounter psychiatric and psychometric evaluation. Their facial EMG will be recorded to assess RFR to dynamic emotional faces created by photo morphing from KDEF emotional faces database, coupled to occulometric recording. Subjects will perform cyberball game as an experimental inclusion or exclusion task and the trustgame task as an implicit evaluation of their prosocial behavior. Questionnaires will assess explicit measurement of social rejection pain and desire of affiliation. Inflammatory markers will be measured in a blood sample before the cyberball task for every subjects and 6 hours later for 20 healthy volunteers. Dosage of IL-6, IL-10, TNFa, IP-10, MCP-1, MIP-1b, Rantes, sIL-6Ra, IL1ra, VEGF, Leptin, PECAM1, sTie2, sVEGFR1, sVEGFR2 will be performed by luminex technique and usCRP, srIL2 ans sCD14 by ELISA technique.
Determine bioequivalence between branded and generic bupropion extended release (XL) products (and between generic products) at steady state in patients with major depressive disorder.
Depression is a leading cause of disability worldwide, affecting nearly 16% of the general population. Its physiopathology remains unclear. Based on gene-environment studies and epigenetic studies, a main hypothesis proposed that the major depressive episode (MDE) results from the convergence of multiple factors including biological factors such as multi-genic vulnerability, hormonal and immunological variations as well as environmental factors. As a consequence, mRNA could define a biological signature of the MDE.
In recent years, measurement-based care (MBC) has been gaining more attention in the treatment of depression because it allows psychiatrists to individualize treatment decisions for each patient based on the change of psychopathology and tolerance toward antidepressants. Several studies, such as the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial using MBC, found that MBC-informed sequential algorithms can be successfully integrated into clinical practice and improve patients' outcomes However, despite a strong theoretical rationale for MBC and data supporting the ability to implement MBC in clinical practice settings, there is currently no randomized controlled trial in MDD patients comparing MBC with usual/standard care. The investigators compare MBC with clinician's treatment decisions, standardizing care to two commonly prescribed antidepressants. Therefore, the aim of this study is to determine the effects of MBC in patients with MDD compared to standard treatment (ST). The research hypothesis is that compared to ST, the estimated time to response and to remission would be significantly shorter in the MBC group without increased dropout rates and side effect burden.
Patients with severe mental illness (SMI) die younger than persons in the general population. Much of the excess mortality for SMI patients is attributable to cardiovascular disease, and is exacerbated by treatment with second-generation antipsychotics (2GAs). Although the cardiovascular risks are well-known, and safe, efficacious therapy exists, few SMI patients receive cardiovascular prevention drugs. Care delivery fragmentation and poor patient adherence are central problems to reducing cardiovascular risks for patients with SMI. To address these problems, we propose to conduct a multi-site, open-label, randomized controlled trial comparing an initial treatment strategy of free, fixed-doses of two generic, cardiovascular prevention drugs (statins and angiotensin drugs) delivered within mental health clinics versus usual treatment. The study will include adult patients (18+ years old) with schizophrenia, schizoaffective disorder, bipolar disorder, major depressive disorder, or psychosis not otherwise specified (NOS) who have received 2GAs treatment within the past six months from within four mental health clinics in the Boston area. We have three aims: 1) to compare the proportions of subjects in each arm who are receiving cardiovascular drug treatment and are adherent to therapy during 12-months of follow-up; 2) to compare changes in composite (e.g., Framingham scores) and individual (e.g., lipid levels) cardiovascular risk factor levels using an intent-to-treat (ITT) approach; and 3) to compare risk factor levels, accounting for variation in adherence over time, using causal inference techniques to estimate the per-protocol effect of the intervention. Our three aims examine whether this low cost, streamlined treatment strategy increases the numbers of subjects receiving cardiovascular prevention therapy and improves cardiovascular risk levels. We will follow subjects for 12 months, and collect interview and biometric data at baseline and over the following 12 months. Subjects will have the option to continue for another 12 months, during which we will continue to collect interview and biometric data, but will not prescribe cardiovascular medications. This population-based initial treatment strategy could be an effective and efficient approach for overcoming traditional barriers to cardiovascular disease prevention within the SMI population. Findings from this study will inform efforts to improve care and outcomes, and to enhance survival for patients with severe mental illness.
Transcranial magnetic stimulation (TMS) is an effective alternative for pharmacotherapy in major depressive disorder, but the effectiveness is not clear due to stimulated region, frequency and intensity of magnet field. Standard TMS techniques only can stimulate superficial cortical areas as the electric field decreases rapidly as a function of tissue depth，while depression is also interconnected with deeper neuronal regions. Deep-brain magnetic stimulation (DSM, or deep TMS, DTMS) allows stimulation of deeper cortical regions. Previous research has demonstrated that alpha frequency (8-13 Hz) EEG activity may have particular relevance to the response to antidepressants, and reduction of alpha frequency (8-13 Hz) could lead to negative symptoms. It has been reported that both alpha frequency and low-field magnetic stimulation could improve depressive symptoms. The objective of this study is to compare the effectiveness of the two different parameters of DMS in the treatment of major depressive disorder. The changes of brain derived neurotropic factor (BDNF) are also investigated to make a relevant analysis of the improvement of depressive symptoms.
The investigators are conducting a research study to learn about the safety and benefit of using a medication called buprenorphine for patients with difficult to treat depression. This research study is testing whether combining two medications will be effective in treating depression when initial treatment with just one antidepressant does not relieve the depressive symptoms; this is what is called "difficult to treat depression" or "treatment resistant depression". The two medications the investigators are using are: an anti-depressant medication called venlafaxine extended release (venlafaxine XR), which is the generic form of Effexor, and buprenorphine. Buprenorphine is a medication that is FDA approved for the treatment of opioid dependence. The investigators are testing whether adding buprenorphine to venlafaxine XR enhances treatment response.