Active clinical trials for "Depressive Disorder"

To evaluate the efficacy and safety of brexpiprazole as adjunctive treatment in elderly patients with Major Depressive Disorder (MDD)

Background: - At least one third of individuals with major depressive disorder (MDD) remain treatment-refractory after receiving currently available antidepressants underscoring the urgent need for new antidepressant therapies. Of the novel pharmacotherapeutic strategies seeking to rapidly alleviate depressive symptoms, glutamatergic modulators have emerged as promising potential targets. The present study sought to examine the potassium (KATP) channel activator diazoxide as a possible treatment for MDD. Diazoxide increases glutamate uptake from the synaptic cleft by activating the KATP channel to chronically increase expression of the excitatory amino acid transporter (EAAT)-2 system in glial cells. Diazoxide is FDA-approved for the treatment of sulfonylurea-induced hypoglycemia, hypoglycemia due to hyperinsulinemia, and hypertension. Objectives: - To assess the ability of diazoxide, potassium channel activator, to improve overall depressive symptomatology in patients with treatment-resistant MDD currently experiencing a major depressive episode. The efficacy of a three-week course of diazoxide will be compared to three weeks of placebo. The MADRS will serve as the main outcome measure Eligibility: - Adults 18 to 65 years old with MDD who are currently depressed without psychotic features. Design: Study Phase I (Day -28 to 0): -- Screen and taper off medications (Days -28 to -14): Prior to consenting to this study, subjects will have undergone a screening consisting of laboratory tests, psychiatric and medical history, and psychiatric and physical examinations under protocol 01-M-0254, "The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Volunteers". After consenting to this study, patients will be tapered off medications. Medications allowed and not allowed are listed in Appendix 1. Patients will be reminded to report all drugs, OTC products, and other agents to the investigators so that they can screen to avoid interactions that might make participation unsafe or might confound the research results. Patients are expected to meet all inclusion and exclusion criteria before medications are tapered (which is usually 1-2 weeks long). Subjects who are not taking medications will enter the drug-free period directly. All participants must have a score of ≥20 on the MADRS at screening and baseline of Study Phase I. Subjects who do not have a score of ≥20 on the MADRS by the end of Study Phase I will be excluded and will receive standard treatment. Drug-free period (Day -14 to day 0): -- Subjects will begin a 2-week drug-free period prior to the administration of diazoxide or placebo. Study Phase II (Day 0 to 56): In this study phase, subjects will be blindly randomized to receive either diazoxide 200-400 mg/day (given BID) or a placebo administered daily by mouth for three weeks. All patients except those who have a 50% or greater decrease in MADRS from baseline at the end of the first cross over point will cross over. To avoid carry-over effects between the different test sessions, there will be an interval of 14-21 days, pending response to test session 1. Subjects will then be blindly crossed over to the second experimental condition (either diazoxide or placebo) for another three weeks. All subjects who discontinue the study or who complete study phase II will then receive either clinical treatment or the opportunity to participate in another research protocol. Patients maintaining response to treatment condition 1 after two weeks will receive an additional one week washout before being crossed over to condition 2.The total duration of the study is approximately 11-13 weeks. The duration of Study Phase I including the 14-day drug-free period is approximately 4 weeks. Study phase II is 8-9 weeks long. Thus, the total duration of the study is approximately 11-13 weeks, except for those patients who were unmedicated at time of entry into the study and therefore do not need to undergo the initial tapering off medications. Subjects will be required to be hospitalized during the entire study. Passes will be permitted if the subject is clinically stable and the pass does not interfere with the study or unit procedures.

In recent years, there has been growing evidence that antidepressants are only marginally effective compared to placebo for mild to moderate depression. In other words, although many people improve when they take antidepressant medications, almost as many get better with placebo pills. One possible solution to this problem would be to give patients a trail of a placebo prior to giving them an antidepressant, however there are ethical issues with doing this deceptively. New evidence from other placebo-responsive disorders such as irritable bowel syndrome shows that people may benefit from placebos even if they know they are taking them. This study aims to determine whether giving placebos without deception to people with major depressive disorder followed by the option to switch to an antidepressant is an effective strategy. There will be 3 groups of subjects. The first group is a standard treatment arm and will receive duloxetine, an antidepressant. The second will be given a placebo with the option to switch to duloxetine if they do not improve. The third group will receive supportive clinical visits the option to switch to duloxetine if they do not improve. This design will allow us to determine whether a sequenced treatment of a placebo without deception and then the option to switch to an antidepressant is a viable strategy. It will also help us to determine to what degree the benefit comes from the ritual of receiving and taking the placebo tablet versus the benefit of visits with a doctor alone. The primary hypothesis is that there will be a less than 5% difference between response rates after 12 weeks in the sequenced placebo-then-antidepressant treatment group (both subjects who have remained on placebo as well as those who have switched to the antidepressant will be considered as one group) compared to the immediate antidepressant therapy group.

The objective of the study is to compare the efficacy of intranasal oxytocin versus intranasal placebo to improve depression symptoms in patients with Major Depressive Disorder (MDD) or Dysthymia Disorder.

Electroconvulsive therapy (ECT), is considered the most effective treatment for severe treatment resistant major depressive disorder (MDD), but it requires about 3 weeks of treatments and can cause considerable acute deficits in memory. It would be a major advance in treatment if ECT could work faster with fewer treatments and result in decrease incidence of memory problems. Ketamine is an excellent candidate for augmentation of ECT because of its acute effects on depression, its short half-life, and its safety profile when given at low doses. Ketamine is given as an infusion and could easily be incorporated into the routine management of patients undergoing ECT, but has never been evaluated prospectively in this context. The investigators propose to assess the efficacy, feasibility, tolerability and safety of N-methyl-D-aspartate antagonist augmentation of ECT using ketamine.

The purpose of this study is to determine the efficacy and safety of Ramelteon, once daily (QD), sublingual (SL), in adult participants with acute depressive episodes associated with Bipolar I disorder.

Most individuals with major depressive disorder manifest clinically significant agitation. Concurrent agitation in a depressed individual is associated with an intensification of mood symptoms, decreased probability of recovery, increased recurrence risk, suicidality, and increased medical-service utilization. The occurrence of anxiety/agitation phenomenology in the depressed patient often invites the need for augmentation strategies (e.g. atypical antipsychotics, benzodiazepines, etc.) and complicated polypharmacy regimens. Moreover, individuals with major depressive disorder often report worsening of symptom severity, irritability, hostility, dysphoria, and significant subjective distress (This response pattern is similar to individuals with bipolar disorder). Results from large research studies provide evidence indicating that quetiapine is capable of offering clinically significant multidimensional symptom relief in bipolar depression. Moreover, results from several trials in major depressive disorder and generalized anxiety disorder have established the efficacy of quetiapine therapy for unipolar depression and anxiety syndromes. So far, no atypical antipsychotic agent has been evaluated specifically for the treatment of agitated depression. In this study, it is hypothesized that persons with major depressive disorder and prominent agitation (i.e. agitated depression) will exhibit a more favourable response and tolerability profile to quetiapine XR when compared to escitalopram.

The primary objectives of this study are to: 1) Evaluate the efficacy of CP 601,927 compared to placebo in the augmentation of antidepressant therapy (ADT) in patients with Major Depressive Disorder (MDD) using the Montgomery Asberg Depression Rating Scale (MADRS). 2) Evaluate the safety and tolerability of CP 601,927 in patients with MDD on ADT.

This will be a multicenter, randomized, double-blind study designed to assess the efficacy, safety and tolerability of an oral Aripiprazole/Escitalopram combination therapy in participants with MDD who have demonstrated an incomplete response to a prospective trial of Escitalopram, and report a treatment history for the current MDD episode of an inadequate response to at least one and no more than three adequate trials of an approved antidepressant other than Escitalopram. An inadequate response is defined as less than a 50% reduction in depressive symptom severity as assessed by the participant's self-report on the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (ATRQ) and evaluated by the investigator as part of the participant's medical and psychiatric history. An adequate trial is defined as an antidepressant treatment for at least 6 weeks duration (or at least 3 weeks for combination treatments) at an approved dose as specified in the ATRQ.

The primary objective of this study is to evaluate the safety and tolerability of long term (6 months) armodafinil treatment as adjunctive therapy to mood-stabilizing medications in adults with bipolar I disorder.