Active clinical trials for "Depressive Disorder"

This is a Phase 2, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy, safety, and tolerability of TNX-601 ER monotherapy versus placebo in patients with Major Depressive Disorder (MDD).

Malawi is a low-income country in sub-Saharan Africa that has limited resources to address a significant burden of disease-including HIV/AIDS. Additionally, depression is a leading cause of disability in the country but largely remains undiagnosed and untreated. Lack of cost-effective, scalable solutions is a fundamental barrier to expanding depression treatment. Against this backdrop, one major success has been the scale-up of a network of more than 700 HIV clinics, with over half a million patients enrolled in ART. As a chronic care system with dedicated human resources and infrastructure, this presents a strategic platform for integrating depression care, and responds to a robust evidence base outlining the bi-directionality of depression and HIV outcomes. The investigators will evaluate a stepped model of depression care that combines group-based Problem Management Plus (group PM+) with antidepressant therapy (ADT) for 420 adults with moderate/severe depression in Neno District, Malawi, as measured by the Patient Health Questionnaire-9 (PHQ-9). Rollout will follow a stepped-wedge cluster randomized design in which 14 health facilities are randomized to implement the model in five steps over a 15-month period. Primary outcomes (depression symptoms, functional impairment, and overall health) and secondary outcomes (e.g. HIV: viral load, ART adherence; diabetes: A1C levels, treatment adherence; hypertension: systolic blood pressure, treatment adherence) will be measured every three months through 12-month follow-up. The investigators will also evaluate the model's cost-effectiveness, quantified as an incremental cost-effectiveness ratio (ICER) compared to baseline chronic care services in the absence of the intervention model. This study will conduct a stepped-wedge cluster randomized trial to compare the effects of an evidence-based depression care model versus usual care on depression symptom remediation as well as physical health outcomes for chronic care conditions. The investigators will also look at the indirect effects of the intervention at the household level. The investigators' hypothesis is that the intervention will be effective at reducing depression symptoms, improving physical health, and improving household members' wellbeing, compare to treatment as usual. The investigators also hypothesize that the intervention will be highly cost-effective, meaning that the cost per QALY gained will be less than Malawi's median GDP per capita. If determined to be effective and cost-effective, this study will provide a model for integrating depression care into HIV clinics in additional districts of Malawi and other low-resource settings with high HIV prevalence.

A 6-cohort single ascending dose (SAD) study will be conducted in healthy volunteers utilizing a slow-infusion intravenous (IV) route of administration. Standard safety, pharmacokinetics (PK) and qEEG monitoring will be evaluated at all dose levels. Subsequently, a 2-cohort multiple ascending dose (MAD) study will be conducted. Doses will be administered on days 1, 4, 8, and 11. Standard safety parameters will be monitored, and PK will be evaluated at all dose levels. Finally, a single-cohort group with received a single dose by slow-infusion IV and have PK samples collected from both blood and cerebrospinal fluid (CSF).

Therapeutic latency, lack of efficacy, and adverse drug reactions are the major concerns in current antidepressant therapies. One-third of the patients with major depressive disorder do not respond to conventional antidepressants that act through the monoaminergic system. To overcome these treatment hurdles, add-on therapy to standard antidepressant drugs may lead to better therapeutic outcomes. The recent discovery of the rapid and sustained antidepressant effect of subanesthetic dose of ketamine led to many extensive clinical and preclinical research in the recent past and has established the possibilities of NMDA receptors as a potential drug target for depression. As repeated doses of ketamine are related to abusive potential and adverse effects, the search for a similar antidepressant agent with a better safety profile is essential. Dextromethorphan has the property of noncompetitively blocking N-methyl-D-aspartate receptors (like ketamine) with additional serotonin transporter and norepinephrine transporter inhibitory action. So, the investigators expect that adding dextromethorphan to selective serotonin reuptake inhibitors (SSRIs) regimen can improve clinical outcomes in major depressive disorder. The literature search found that to date, there is no randomized controlled trial on Dextromethorphan as add-on therapy to first-line antidepressants like SSRIs. So, the present randomized controlled trial has been planned to evaluate the efficacy and safety of add-on dextromethorphan to SSRIs in major depressive disorder.

Examine the safety and effectiveness of the Fisher Wallace Cranial Electrotherapy Stimulator Device on Major Depressive Disorder using two 20-minute per day treatment sessions over eight weeks.

Objective: Chronic epidural cortical stimulation (ECS) involves the neurosurgical placement of an electric wire on the surface of the brain with intermittent activation. Over time, ECS modulates local and distal connected brain regions. It is being currently applied over the motor cortex to treat intractable pain. Because of the important role played by the medial prefrontal cortex in mood regulation, the goal of this study is to apply this minimally invasive neurostimulation modality over medial prefrontal cortex in severely ill depressed subjects who have failed all other attempts at treatment.

This study will investigate the feasibility, safety, and tolerability of administering repetitive Transcranial magnetic stimulation(TMS) at frequencies other than standard 10 Hz. This study will enroll 10 subjects who will undergo one quantitative electroencephalograph, one TMS procedure to determine the appropriate frequency and intensity for treatment, weekly mood/symptom assessments, and up to 30 TMS treatments. Subjects will be asked to participate for up to 6 weeks.

Adults with serious mental illness (SMI) are disproportionately affected by medical comorbidity, earlier onset of disease, and 10 to 25 years reduced life expectancy compared to the general population. These high rates of morbidity and early mortality are associated with inadequately managed medical and psychiatric illnesses. A recent systematic review found nine effective self-management interventions that address medical and psychiatric illnesses in adults with SMI. However, there has been limited adoption of these interventions due to both provider and consumer-based factors. Provider-based barriers consist of the lack of an adequate workforce with the capacity, time, and knowledge of effective approaches to self-management support for adults with SMI and chronic health conditions. Consumer-based barriers associated with limited participation in self-management programs include lack of access, engagement, and ongoing community-based support for persons with SMI. Peer support specialists have the potential to address these barriers as they comprise one of the fastest growing sectors of the mental health workforce, have "lived experience" in self-management practices, and offer access to support in the community. However, challenges need to be resolved for peers to be effective providers of evidence-based interventions. For example, peers are frequently trained to provide "peer support" described as "giving and receiving help founded on key principles of respect, shared responsibility, and mutual agreement of what is helpful". Peer support has been associated with increased sense of control, ability to make changes, and decreased psychiatric symptoms. Despite benefits, peer support does not adhere to evidence-based practices for psychiatric and medical self-management and does not follow protocols that ensure fidelity and systematically monitor outcomes. The investigators hypothesize that mobile technology has the potential to overcome these limitations of peer support by providing real-time guidance in fidelity adherent delivery of a peer-delivered, technology-assisted evidence-based self-management intervention (PDTA-IIMR). The investigator will build the necessary expertise to pursue a career developing and testing novel approaches to peer-delivered evidence-based self-management interventions. Training will include: development of peer-delivered interventions; development and design of mobile health-supported interventions; and intervention clinical trials research. Concurrently, this study includes refinement of the intervention protocol with input from peers and consumers and conducting a pilot study evaluating the feasibility and potential effectiveness of PDTA-IIMR compared to routine peer support for N=6 peers and N=40 adults with SMI and chronic health conditions. Outcomes include feasibility, medical and psychiatric self-management skills, functional ability, and mortality risk factors and examine self-efficacy and social support as mechanisms on outcomes.

Diabetes characterized by decreased production, or resistance to the action of insulin or both. The reduced production or action alters many important body functions namely glucose absorption and utilization in the body. The disturbed glucose metabolism profoundly effects transportation of large neutral amino acids especially tryptophan in brain leading decreased synthesis of serotonin and hence ensuing depression, memory loss and various other psycho-neurological problems. Different antipsychotic treatments like serotonin reuptake inhibitors, monoamine inhibitors and tricyclic antidepressants are available in the market to treat depression but are not devoid of adverse effects. Therefore, there is a tendency in underdeveloped countries to use alternative remedies to combat the psycho-neurological issues. Nature has bestowed the bounty of indigenous herbs like Saffron (Crocus sativusL) and chamomile (Matricaria chamomileL), that possess neuro-protective effects and are regularly consumed in day to day delicacies with no documented adverse-effects nor adverse events Though these herbs have been studied widely for their multiple therapeutic benefits, however, till date both of these herbs in combination have not been studied as an adjuvant therapy for mild to moderate depression. Therefore the present study is designed to determine the combined beneficial effects of these herbs as an adjuvant therapy for treatment of depression.

Cognitive behavioral therapy (CBT) is a brief, efficient, and effective psychotherapy for individuals with depressive and PTSD. However, CBT is largely underutilized within Veteran Affairs Medical Centers (VAMCs) due to the cost and burden of trainings necessary to deliver the large number of CBT protocols. Transdiagnostic Behavior Therapy (TBT), in contrast, is specifically designed to address numerous distinct disorders within a single protocol. The transdiagnostic approach of TBT has the potential to dramatically improve the accessibility of CBT within VAMCs and therefore improve clinical outcomes of Veterans. The proposed research seeks to evaluate the efficacy of a group version of TBT (G-TBT) by assessing clinical outcomes and quality of life in VAMC patients with major depressive disorder and PTSD throughout the course of treatment and in comparison to two existing group disorder-specific therapies (G-DST), CBT for Depression and Cognitive Processing Therapy for PTSD.