Resistant major depression

BACKGROUND: A seminal study found higher subgenual frontal cortex resting-state connectivity with 2 left ventral frontal regions and the dorsal midbrain to predict better response to psychotherapy versus medication in individuals with treatment-naïve major depressive disorder (MDD). Here, we examined whether these subgenual networks also play a role in the pathophysiology of clinical outcomes in MDD with early treatment resistance in primary care. METHODS: Forty-five people with current MDD who had not responded to ≥2 serotonergic antidepressants ( n  = 43, meeting predefined functional magnetic resonance imaging minimum quality thresholds) were enrolled and followed over 4 months of standard care...

The compound N -(3-(phenylselanyl)prop-2-yn-1-yl)benzamide (SePB), which combines a selenium atom and a benzamide nucleus in an organic structure, has demonstrated a fast antidepressant-like effect in mice. This action is influenced by the serotonergic system and represents a promising development in the search for novel antidepressant drugs to treat major depressive disorder (MDD), which often resists conventional treatments. This study aimed to further explore the mechanism underlying the antidepressant-like effect of SePB by investigating the involvement of the dopaminergic and noradrenergic systems in the tail suspension test (TST) in mice and evaluating its pharmacokinetic profile in silico...

RATIONALE: Major Depressive Disorder (MDD) significantly impairs the quality of life for those affected. While the exact causes of MDD are not fully understood, the deficit of monoamines, especially serotonin and noradrenaline, is widely accepted. Resistance to long-term treatments and adverse effects are often observed, highlighting the need for new pharmacological therapies. Synthetic organic compounds containing selenium have exhibited pharmacological properties, including potential antidepressant effects...

Previous studies suggested effectiveness of psilocybin in the field of mental health. FDA designated psilocybin as a "breakthrough therapy" for the treatment of treatment-resistant depression (TRD) in 2018. This paper provided a review of psilocybin's potential role in treatment of depression by focusing on published clinical trials. Studies showed that psilocybin, an agonist on 5-HT2A receptors, manifests antidepressant and anxiolytic effects by increasing glutamate transmission, reducing brain inflammation, decreasing default mode network activity...

For the first time after many decades, many new antidepressants have been approved and many more are under various stages of development and will soon be available in the market. The new drugs present a range of new mechanisms of action with benefits in terms of speed of action, tolerability and range of treatable disorders. Neurosteroids have been recently approved and their rapid benefit may extend from postpartum depression to anxious depression and bipolar depression, dextromethorphan and bupropion combination may prove useful in major depression but also in treatment resistant depression, dextromethadone is a possible augmentation in partial antidepressant response, psychedelic drugs have the potential of long lasting benefits after a single administration, though are still experimental treatments...

One in five people will likely suffer from major depressive disorder (MDD) during their life. Thirty percent of those with MDD will experience Treatment Resistant Depression (TRD), which is characterized by a failure to respond to two adequately administered trials of antidepressants. Esketamine is a rapidly acting intranasal antidepressant. Present-day Esketamine research has limited data in real-world populations. This study aimed to assess Esketamine treatment in a real-world community-based population. This naturalistic retrospective study included 94 individuals age 18 and above diagnosed with TRD, treated with Esketamine in an outpatient setting...

UNLABELLED: Many adults with major depressive disorder (MDD) do not receive effective treatment. The potential benefits of resistance exercise training (RET) are understudied and may be mechanistically related to cerebral blood flow changes. PURPOSE: To assess feasibility, acceptability, and preliminary efficacy of a 16-week, theory-informed RET trial for the treatment of MDD and explore changes in cerebral blood flow. METHODS: Ten adults with DSM-5-diagnosed MDD were enrolled in a single-arm, 16-week, twice-weekly, whole-body RET intervention, consistent with US and WHO Physical Activity resistance exercise guidelines...

Although there are various treatments available for depression, some patients may experience resistance to treatment or encounter adverse effects. Centella asiatica (C. asiatica) is an ancient medicinal herb used in Ayurvedic medicine for its rejuvenating, neuroprotective and psychoactive properties. This study aims to explore the antidepressant-like effects of the major constituents found in C. asiatica, i.e., asiatic acid, asiaticoside, madecassic acid, and madecassoside at three doses (1.25, 2.5, and 5mg/kg, i...

BACKGROUND: Treatment resistant depression (TRD) is a subset of major depressive disorder (MDD) in which symptoms do not respond to front line therapies. In older adults, the assessment and treatment of TRD is complicated by psychosocial risk factors unique to this population, as well as a relative paucity of research. METHODS: Narrative review aimed at (1) defining TRLLD for clinical practice and research; (2) describing psychosocial risk factors; (3) reviewing psychological and non-pharmacological treatments; (4) discussing the role of clinical phenotyping for personalized treatment; and (5) outlining research priorities...

UNLABELLED: Despite the abundance of literature on treatment-resistant depression (TRD), there is no universally accepted definition of TRD, and available treatment pathways for the management of TRD vary across the Latin American region, highlighting the need for a uniform definition and treatment principles to optimize the management of TRD in Latin America. METHODS: Following a thematic literature review and pre-meeting survey, a Latin America expert panel comprising 14 psychiatrists with clinical experience in managing patients with TRD convened and utilized the RAND/UCLA appropriateness method to develop consensus-based recommendations on the appropriate definition of TRD and principles for its management...

INTRODUCTION: Treatment-resistant depression (TRD) is commonly defined as the failure of at least two trials with antidepressant drugs, given at the right dose and for an appropriate duration. TRD is associated with increased mortality, compared to patients with a simple major depressive episode. This increased rate was mainly attributed to death from external causes, including suicide and accidents. The aim of our study is to identify socio-demographic and psychopathological variables associated with suicidal attempts in a sample of outpatients with TRD...

BACKGROUND: During hospitalisation, older patients spend most of their time passive in bed, which increases the risk of functional decline and negative adverse outcomes. Our aim is to examine the impact of robot-assisted physical training on functional status in older geriatric patients during acute hospitalisation. METHODS: This is a single-centre investigator-blinded placebo-controlled randomised controlled trial including geriatric patients aged ≥ 65 years, able to ambulate before hospitalisation, and with expected length of stay ≥ 2 days...

BACKGROUND: RECOVER is a randomized sham-controlled trial of vagus nerve stimulation and the largest such trial conducted with a psychiatric neuromodulation intervention. OBJECTIVE: To describe pre-implantation baseline clinical characteristics and treatment history of patients with unipolar, major depressive disorder (MDD), overall and as a function of exposure to interventional psychiatric treatments (INTs), including electroconvulsive therapy, transcranial magnetic stimulation, and esketamine...

BACKGROUND: Catatonia has been increasingly associated with mood disorders and is recognized as a specifier in the DSM-5 and DSM-5-TR. The DSM-5-TR recognizes melancholia as a specifier for depressive episodes in major depressive disorder and bipolar disorder. It is characterized by severe anhedonia, lack of reactivity, excessive or delusional guilt, and significant vegetative symptoms. As the conceptualization of melancholia expanded beyond its mood components to include psychomotor disturbances, its overlap with psychomotor symptoms or catatonia becomes evident...

BACKGROUND: Persistent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), reactivation of dormant viruses, and immune-oxidative responses are involved in long COVID. OBJECTIVES: To investigate whether long COVID and depressive, anxiety, and chronic fatigue syndrome (CFS) symptoms are associated with IgA/IgM/IgG to SARS-CoV-2, human herpesvirus type 6 (HHV-6), Epstein-Barr Virus (EBV), and immune-oxidative biomarkers. METHODS: We examined 90 long COVID patients and ninety healthy controls...

BACKGROUND: Electrophysiologic measures provide an opportunity to inform mechanistic models and possibly biomarker prediction of response. Serotonergic psychedelics (SPs) (i.e., psilocybin, lysergic acid diethylamide (LSD)) and ketamine represent new investigational and established treatments in mood disorders respectively. There is a need to better characterize the mechanism of action of these agents. METHODS: We conducted a systematic review investigating the spectral signatures of psilocybin, LSD, and ketamine in persons with major depressive disorder (MDD), treatment-resistant depression (TRD), and healthy controls...

OBJECTIVE: Psychomotor retardation is a core clinical component of Major Depressive Disorder responsible for disability and is known as a treatment response marker of biological treatments for depression. Our objective was to describe cognitive and motoric measures changes during a treatment by repetitive Transcranial Magnetic Stimulation (rTMS) within the THETAD-DEP trial for treatment-resistant depression (TRD), and compare those performances at the end of treatment and one month after between responders (>50% improvement on MADRS score), partial responders (25-50%) and non-reponders (no clinically relevant improvement)...

IMPORTANCE: Antidepressant responses and the phenotype of treatment-resistant depression (TRD) are believed to have a genetic basis. Genetic susceptibility between the TRD phenotype and other psychiatric disorders has also been established in previous genetic studies, but population-based cohort studies have not yet provided evidence to support these outcomes. OBJECTIVE: To estimate the TRD susceptibility and the susceptibility between TRD and other psychiatric disorders within families in a nationwide insurance cohort with extremely high coverage and comprehensive health care data...

Mitochondrial dysfunction has been suggested to play a role in depression pathogenesis. This clinical trial (jRCTs042220011) was conducted to evaluate whether depression symptoms could be alleviated by an Extremely Low Frequency, Extremely Low Magnetic Environment (ELF-ELME), which has been found in basic research studies to enhance mitochondrial membrane potential. Participants were exposed to the ELF-ELME via a head-mounted magnetic field device (10 μTesla, 4 ms, 1-8 Hz/8 s) worn for 2 h per day for 8 consecutive weeks...

BACKGROUND: Ketamine is the prototypal rapid-acting antidepressant (RAAD) for TRD with approved indication for esketamine-nasal spray (ESK-NS). Distinctly, arketamine (R-KET) demonstrates enhanced antidepressant effects and neuroplasticity changes compared to esketamine, with fewer dissociative side effects and abuse potential. This study focuses on R-ketamine's therapeutic implications, safety, and tolerability in TRD treatment. METHODS: We report on a year-long follow-up of three TRD patients post-single IV R-KET administration...