Treatment Of Major Depressive Disorder Research Articles

Ketamine infusions for treatment-resistant bipolar depression: Commentary.

Ketamine infusions for treatment-resistant bipolar depression: Commentary.

Maintenance repetitive transcranial magnetic stimulation (rTMS) therapy for treatment-resistant depression: a study protocol of a multisite, prospective, non-randomized longitudinal study

BackgroundRepetitive transcranial magnetic stimulation (rTMS) is a widely used treatment for major depressive disorder (MDD), and its effectiveness in preventing relapse/recurrence of MDD has been explored. Although few small sample controlled studies exist, the protocols of maintenance rTMS therapy were heterogeneous and evidence of its effectiveness is not sufficient. Thus, this study aims to evaluate whether maintenance rTMS is effective in maintaining the treatment response in patients with MDD with a large sample size and feasible study design.MethodsIn this multicenter open-labelled parallel-group trial we plan to recruit 300 patients with MDD who have responded or remitted to acute rTMS therapy. Participants would be classified into two groups according to their preference; the maintenance rTMS and pharmacotherapy group, and the pharmacotherapy only group. The protocol of maintenance rTMS therapy is once a week for the first six months and once biweekly for the second six months. The primary outcome is the relapse/recurrence rates during 12 months following enrollment. Other measures of depressive symptoms and recurrence/relapse rates at different time points are the secondary outcomes. The primary analysis is the between-group comparison adjusted for background factors using a logistic regression model. We will perform the group comparison with inverse probability of treatment weighting as the sensitivity analysis to ensure the comparability of the two groups.DiscussionWe hypothesize that maintenance rTMS therapy could be an effective and safe treatment for preventing depressive relapse/recurrence. Considering the limitation of potential bias owing to the study design, we plan to use statistical approaches and external data to avoid overestimation of the efficacy.Trial registrationJapan Registry of Clinical Trials, ID: jRCT1032220048. Registered 1 May 2022.

Effects of Psychotherapy on Glutamatergic Neurotransmission

Introduction: Psychodynamic psychotherapy is an effective and widely used treatment for major depressive disorder (MDD); however, little is known about neurobiological changes associated with induced symptom improvement. Methods: Proton magnetic resonance spectroscopy with a two-dimensional J-resolved sequence served to test the relationship between glutamate (Glu) and glutamine (Gln) levels, measured separately in pregenual anterior cingulate cortex (pgACC) and the anterior midcingulate cortex (aMCC) as a control region, with change in depression symptoms after 6 months of weekly psychodynamic psychotherapy sessions in MDD patients. Depressed (N = 45) and healthy (N = 30) subjects participated in a baseline proton magnetic resonance spectroscopy measurement and a subgroup of MDD subjects (N = 21) then received once-a-week psychodynamic psychotherapy and participated in a second proton magnetic resonance spectroscopy measurement after 6 months. Change in depression symptoms was assessed using the Hamilton Depression Rating Scale (HAMD). Results: Higher pretreatment pgACC Gln concentrations in MDD patients compared to healthy controls were associated with symptom severity. Patients and controls did not differ regarding Gln levels in aMCC nor regarding Glu levels in both regions. The association of pgACC Gln concentration and severity of depressive symptoms was reversed after 6 months of psychotherapy in MDD subjects. Regarding Gln in aMCC as well as Glu in both regions, there were no significant associations with improvement of depressive symptoms in the course of psychotherapy. Discussion: Findings indicate specific regional effects of psychodynamic psychotherapy on glutamatergic neurotransmission and thereby highlight the key role of the pgACC in both depression pathophysiology and recovery.

The effective on intradermal acupuncture based on changes in biological specificity of acupoints for major depressive disorder: study protocol of a prospective, multicenter, randomized, controlled trial

BackgroundAntidepressants still have some side effects in treating major depressive disorder (MDD), and acupuncture therapy is a complementary therapy of research interest for MDD. Acupoints are sensitive sites for disease response and stimulation points for acupuncture treatment. Prior studies suggest that the biological specificity of acupoints is altered in physiological and pathological situations. Therefore, we hypothesize that the biological specificity of acupoints is associated with the diagnosis of MDD and that stimulating acupoints with significant biological specificity can achieve a better therapeutic effect than clinical common acupoints. This study aims to investigate the efficacy and safety of intradermal acupuncture (IA) treatment for MDD based on changes in the biological specificity of acupoints.MethodsThe first part of the study will enroll 30 MDD patients and 30 healthy control (HC) participants to assess pain sensitivity and thermal specificity of MDD-related acupoints using a pressure pain threshold gauge (PTG) and infrared thermography (IRT). The potentially superior acupoints for treating MDD will be selected based on the results of PTG and IRT tests and referred to as pressure pain threshold strong response acupoints (PSA) and temperature strong response acupoints (TSA).The second part of the study will enroll 120 eligible MDD patients randomly assigned to waiting list (WL) group, clinical common acupoint (CCA) group, TSA group, and PSA group in a 1:1:1:1 ratio. The change in the Patient Health Questionnaire-9 Items (PHQ-9), the MOS item short-form health survey (SF-36), pressure pain threshold, temperature of acupoints, and adverse effects will be observed. The outcomes of PHQ-9 and SF-36 measures will be assessed before intervention, at 3 and 6 weeks after intervention, and at a 4-week follow-up. The biological specificity of acupoint measures will be assessed before intervention and at 6 weeks after intervention. All adverse effects will be assessed.DiscussionThis study will evaluate the therapeutic effect and safety of IA for MDD based on changes in the biological specificity of acupoints. It will investigate whether there is a correlation between the biological specificity of MDD-related acupoints and the diagnosis of MDD and whether stimulating strong response acupoints is superior to clinical common acupoints in the treatment of MDD. The study’s results may provide insights into the biological mechanisms of acupuncture and its potential as a complementary therapy for MDD.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT05524519.

Major depression disorder - etiology and treatment

Introduction and purpose: The problem of major depression disorder (MDD) affects more and more people. In a few years, it may become the most common disease after cardiovascular diseases and cancer. MDD are manifested by a depressed mood, decreased energy, loss of interest and the ability to enjoy life, as well as a number of other additional symptoms. Untreated MDD can lead to disability. This entails not only consequences for the sick person but also increased social costs. That is why it is so important to know the causes of its formation and to look for new therapeutic methods.
 State of knowledge: The development of MDD is influenced by genetic factors, inflammatory factors and hormonal disorders, changes in the structure of the brain, disorders in neurotransmission. The microbiome-gut-brain axis affects mood regulation and neurotransmission in the brain. Bacteria such as Escherichia, Shigella, Enterococcus, Streptococccus, Alistipes, Parabacterioides, Veillonella have been identified as having a potential negative effect on the development of MDD and response to treatment. The use of probiotics containing Lactobacillus helveticus R0052, Bifidobacterium longum and Clostridium butyricum MIYAIRI 588 may help reduce the symptoms of MDD. In recent years, the US Food and Drug Administration (FDA) has approved the intranasal preparation of esketamine for the treatment of treatment-resistant depression and major depressive disorder with severe suicidal thoughts. Unlike other antidepressants, it has a quick effect on reducing symptoms.
 Summary: Due to the global problem of MDD, further research is needed to better understand the mechanisms of its formation. Particular attention should be paid to the influence of microbiota.

EE248 Patient-Informed Value Elements for Economic Evaluation of Treatment for Major Depressive Disorder: A Systematic Review and Synthesis

Our recent study in individuals with major depressive disorder (MDD) elicited six prioritized attributes in selecting treatments to manage their condition: Treatment Mode, Time to Treatment Effect, MDD Relief, Quality of Work, Interaction with Others, and Affordability. This study aims to identify whether previous cost-effectiveness analyses (CEAs) in MDD addressed these patient-important attributes, whether patients were engaged in the modeling process, and whether patient preferences for treatment attributes were incorporated into the economic evaluations.

Epidemiological overview of major depressive disorder in Scandinavia using nationwide registers.

Major depressive disorder (MDD) is a common psychiatric disorder associated with a high disease burden. This study gives a comprehensive overview of the prevalence, outcomes, treatment, and genetic epidemiology of MDD within and across the Scandinavian countries. This study has aimed to assess and compare across Norway, Denmark, and Sweden 1) the prevalence and trajectories of MDD and comorbidity, 2) outcomes and treatment, and 3) heritability (Denmark and Sweden only). The analyses leveraged data on 272,944 MDD cases (and 6.2 million non-cases) from Norway, Sweden, and Denmark in specialist care in national longitudinal health registers covering 1975-2013. Relying on harmonized public data global comparisons of socioeconomic and health metrics were performed to assess to what extent findings are generalizable. MDD ranked among the most prevalent psychiatric disorders. For many cases, the disorder trajectory was severe, with varying proportions experiencing recurrence, developing comorbid disorders, requiring inpatient treatment, or dying of suicide. Important country differences in specialist care prevalence and treatment were observed. Heritability estimates were moderate (35-48%). In terms of socioeconomic and health indices, the Scandinavian nations were comparable to one another and grouped with other Western nations. The Scandinavian countries were similar with regards to MDD epidemiological measures, but we show that differences in health care organization need to be taken into consideration when comparing countries. This study demonstrates the utility of using comprehensive population-wide registry data, outlining possibilities for other applications. The findings will be of use to policy makers for developing better prevention and intervention strategies. Swedish Research Council (Vetenskapsrådet, award D0886501 to PFS), US National Institutes of Mental HealthR01 MH123724 (to PFS), European Union's Horizon 2020 Research and Innovation Program (847776 and 964874, to OA) and European Research Council grant (grant agreement ID 101042183, to YL).

Real-world treatment modalities, health care resource utilization, and costs among commercially insured patients with newly diagnosed major depressive disorder in the United States.

BACKGROUND: In the United States, major depressive disorder (MDD) is one of the most prevalent mental health disorders. Treatment guidelines for MDD recommend pharmacologic and nonpharmacologic therapies tailored to the patient's disease severity, level of function, and comorbid health conditions. While previous studies examined real-world pharmacologic treatment patterns and costs among patients with MDD, few have examined the use of nonpharmacologic treatments and their association with health care resource utilization (HCRU) and cost. OBJECTIVE: To describe prevalence and associations between patient/provider characteristics and treatment modality and characterize HCRU and cost by treatment modality for patients with newly diagnosed MDD. METHODS: Commercially insured US patients, aged 18-62 years with newly diagnosed MDD between January 1, 2017, and September 30, 2019, were retrospectively identified from the Healthcare Integrated Research Database. Eligible patients were continuously enrolled in the health plan for 1 year before and 2 years after the first MDD diagnosis (index date). Those with co-occurring schizophrenia, bipolar disorder, postpartum depression, substance use disorder, and any prior MDD treatments were excluded. Treatment modalities assessed in the 2-year post-index period included antidepressant only (Rx-only), nonpharmacologic only (non-Rx-only), both antidepressant and nonpharmacologic (combination), and no treatment. HCRU and costs were assessed in the 2-year post-index period by treatment modality. Regression models identified associations between patient/provider characteristics and treatment modality, and the relationship between treatment modality and MDD severity changes. RESULTS: In total, 12,657 patients were included (mean age: 36 years; 60% female). During follow-up, 34% of patients received Rx-only, 25% received non-Rx-only, 28% received combination, and 13% received no treatment. MDD severity at diagnosis (26% mild, 54% moderate, 20% severe) was available for 51% of patients. Post-index inpatient hospitalizations were 11% for those with Rx-only, 10% for non-Rx-only, 16% for combination, and 29% for no treatment, whereas all-cause mean monthly total costs were $792, $633, $786, and $1,292, respectively. In multinomial logistic regression, age, sex, geographic region and urbanicity of patient residence, socioeconomic status, diagnosing provider specialty, and initial diagnosis location were significantly associated (P < 0.05) with treatment modality. In multivariable logistic regression, recipients of Rx-only (odds ratio = 2.03, P < 0.01) or combination (odds ratio = 3.26, P < 0.01) had higher odds of improving MDD severity than patients who received no treatment. CONCLUSIONS: In this real-world sample of commercially insured patients, we observed variations in outcomes by treatment modality and an association between treatment modality and disease severity. Further research is needed to explore the underlying causal relationships between treatment modality and patient outcomes. Study Registration: https://doi.org/10.17605/OSF.IO/YQ6B3 DISCLOSURES: Dr Grabner is an employee of Carelon Research, which received funding from the Innovation and Value Initiative for the conduct of the study on which this manuscript is based. Ms Pizzicato and Mr Yang were employees of Carelon Research at the time the study was conducted. Dr Grabner is a shareholder of Elevance Health. Drs Xie and Chapman are employees of the Innovation and Value Initiative.

PCR113 Treatment Preferences Among Adults with Reduced Productivity Due to Depression

Productivity is often considered in economic evaluation, but its importance to adults living with major depressive disorder (MDD) is unclear. Our objective was to quantify preferences for MDD treatment among adults with reduced productivity due to their MDD.

P47 A Discrete Choice Experiment to Assess Patient-Informed Preferences for Major Depressive Disorder Treatment By Depression Severity

P47 A Discrete Choice Experiment to Assess Patient-Informed Preferences for Major Depressive Disorder Treatment By Depression Severity

Design, implementation and preliminary results of a type-2 hybrid cluster-randomized trial of integrating screening and treatment for major depressive disorder into specialty clinics providing opioid agonist therapies in Ukraine

IntroductionUkraine has a high prevalence of co-occurring disorders (COD), defined as having both substance use (SUD) and psychiatric disorders. Major depressive disorder (MDD) is the most prevalent psychiatric disorder among people with SUD. People with COD experience poor health outcomes, and international agencies propose integrated COD care. In Ukraine, treatment for SUD is delivered in specialized substance use clinics, without providing any other medical services for comorbidities, including MDD. Here we present the protocol, along the with the preliminary results of the MEDIUM project, including observations over the first 6 months. MethodsA cluster-randomized type-2 hybrid trial was conducted to integrate MDD treatment into specialty clinics providing opioid agonist therapies (OAT) in Ukraine. Twelve clinics in four regions underwent randomization to control (N = 1) vs experimental arms (N = 2) in each region. Clinicians at experimental sites received tele-education through modified project ECHO using a facilitated screening, evaluation, and treatment algorithm of depression, with or without financial incentives. Service-, patient- and provider-level data were collected for the analysis every 6 months for 24 months. Preliminary resultsFor service delivery outcomes, 4421 patients enrolled on OAT across all sites were assessed for MDD for screening (76.7%), evaluation with diagnosis (43.5%) and treatment (30.7%) for MDD; 13.8% continued treatment at least for 6 months. For patient-level outcomes, 1345 patients and 54 providers participated in serial surveys every six months. ConclusionThis study will be the first to explore integrated COD care in Ukraine and generate evidence on effective service integration and delivery strategies for people with COD receiving treatment at substance use clinics with broader implications for Eastern Europe and Central Asia region.

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A Genotypes and Serotonin Reuptake Inhibitor Antidepressants.

Serotonin reuptake inhibitor antidepressants, including selective serotonin reuptake inhibitors (SSRIs; i.e., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline), serotonin and norepinephrine reuptake inhibitors (i.e., desvenlafaxine, duloxetine, levomilnacipran, milnacipran, and venlafaxine), and serotonin modulators with SSRI-like properties (i.e., vilazodone and vortioxetine) are primary pharmacologic treatments for major depressive and anxiety disorders. Genetic variation in CYP2D6, CYP2C19, and CYP2B6 influences the metabolism of many of these antidepressants, which may potentially affect dosing, efficacy, and tolerability. In addition, the pharmacodynamic genes SLC6A4 (serotonin transporter) and HTR2A (serotonin-2A receptor) have been examined in relation to efficacy and side effect profiles of these drugs. This guideline updates and expands the 2015 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and SSRI dosing and summarizes the impact of CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A genotypes on antidepressant dosing, efficacy, and tolerability. We provide recommendations for using CYP2D6, CYP2C19, and CYP2B6 genotype results to help inform prescribing these antidepressants and describe the existing data for SLC6A4 and HTR2A, which do not support their clinical use in antidepressant prescribing.

Cariprazine (Vraylar) for adjunctive treatment of depression.

The FDA has approved the second-generation antipsychotic drug cariprazine (Vraylar — Abbvie) for adjunctive treatment of major depressive disorder (MDD) in adults. Cariprazine was previously approved for treatment of schizophrenia and bipolar depression, and for acute treatment of manic or mixed episodes associated with bipolar I disorder.

The Pharmacokinetics and Bioequivalence of Desvenlafaxine Succinate in Chinese Healthy Subjects Under Fasting and Fed States.

Desvenlafaxine succinate is a selective serotonin-norepinephrine reuptake inhibitor for the treatment of major depressive disorder. The pharmacokinetic profile of desvenlafaxine succinate at the clinically recommended dose of 50mg in Chinese healthy subjects has been reported rarely. The objective of this study was to evaluate the pharmacokinetics and bioequivalence of desvenlafaxine succinate in Chinese healthy subjects. A single-dose, open-label, randomized, two-way crossover study with a 7-day washout period was conducted. A total of 88 individuals were incorporated to show bioequivalence of a generic and a reference drug, with 48 individuals in the fasting state and 40 receiving a high-fat diet. Finally, 46 and 38 individuals completed the fasting and the fed study, respectively. The 90% confidence intervals of the adjusted geometric mean ratios for maximum plasma concentration, area under the concentration-time curve from time zero to the last measurable concentration, and area under the concentration-time curve from time zero to infinity all fell in the bioequivalent interval of 80%-125% in both the fasting and fed states. A total of 33 adverse events were reported, and all were mild or moderate in severity. In summary, the generic and reference formulations were bioequivalent, with no observable safety differences in the fasting/fed state.

Effect of fluvoxamine on plasma interleukin-6 in patients with major depressive disorder: a prospective follow-up study.

Major depressive disorder (MDD) is associated with low-grade inflammation, and anti-inflammatory treatment can help improve depressive symptoms. A recent study found that fluvoxamine (FLV) can reduce Interleukin-6 (IL-6) production via sigma-1 receptor in inflammation models. However, the anti- IL-6 effect of FLV in treating patients with MDD and whether it can contribute to antidepressant effects remain unclear. A total of 65 patients with MDD and 34 healthy controls were recruited at baseline, and 50 patients completed the FLV treatment for 2 months. We assessed depression and anhedonia and collected plasma IL-6 levels at baseline, 1 month, and 2 months after baseline. This study evaluated the changes in clinical measures and IL-6 during treatment and analyzed their association. Further subgroup analyses were conducted in patients with MDD with high, medium, or low IL-6. Depression and anhedonia were significantly improved in patients with MDD, while the IL-6 did not significantly change after the FLV treatment. However, IL-6 significantly declined after the FLV treatment among patients with MDD with higher baseline IL-6. No significant associations were found between the changes in depressive symptoms and IL-6. Our study provided preliminary evidence suggesting that the anti-IL-6 effect of FLV might not play a vital role in its antidepressant treatment, at least in patients with MDD with low inflammation. However, for patients with MDD with higher IL-6, FLV can help reduce IL-6 significantly in the antidepressant treatment, which may help guide the individual treatment of MDD with higher IL-6 levels. https://clinicaltrials.gov/ct2/show/NCT04160377, identifier NCT04160377.

N°229 – Is baseline high threshold on motor evoked potential a predictor of good rTMS response for the treatment of major depressive disorder?

N°229 – Is baseline high threshold on motor evoked potential a predictor of good rTMS response for the treatment of major depressive disorder?

Balancing the beautiful and the good in pursuit of biomarkers for depression.

Balancing the beautiful and the good in pursuit of biomarkers for depression.

Implementing Digital Cognitive-Behavioral Therapy for Major Depressive Disorder in Routine Psychiatric Appointments: A Pilot Project in a Rural Population.

Psychotherapy is well-established as an effective treatment for major depressive disorder (MDD). However, many individuals with MDD in rural areas of the United States do not have access to psychotherapy. Self-management (SM) strategies are now the standard of care for chronic medical conditions and may be a viable alternative for individuals without access to psychotherapy. The current article describes the implementation of a 13-week pilot project to integrate digital cognitive-behavioral therapy (dCBT) SM programs into routine psychiatric advanced practice nurse (APN) telehealth appointments in the rural United States. Eight participants completed the project. The project did not meet the benchmark of 20 participants to improve access to treatment; however, one half (n = 4) of participants reported clinically significant improvement in MDD symptoms over 6 weeks. For clients without access to psychotherapy, dCBT SM programs can be effective in improving individual client outcomes when implemented by APNs in routine telehealth appointments. [Journal of Psychosocial Nursing and Mental Health Services, 61(10), 44-51.].

White matter microstructure changes in adults with major depressive disorder: evidence from diffusion magnetic resonance imaging

Major depressive disorder (MDD) is a serious psychiatric disorder marked by low mood and anhedonia. Understanding the neural mechanism of MDD is essential for the treatment of depression. White matter fibres, connecting different computational units in the brain, have an important effect on brain function; however, the mechanism of white matter fibre abnormality in MDD is still unclear. Our study expected to find white matter abnormalities associated with the frontal lobe and hippocampus in individuals with MDD. Using diffusion tensor imaging data and tract-based spatial statistics, we investigated the microstructural differences in white matter fibre tracts between 30 adults with MDD compared with 31 healthy controls, and calculated the association between MDD-related microstructural changes and illness duration. It was found that patients with MDD showed reduced fractional anisotropy in the genu and body of the corpus callosum, right corona radiata and part of the thalamic radiations, suggesting lower fibrous myelination levels in these regions; the decreased fractional anisotropy in these regions was associated with longer illness duration. Our results suggest that MDD may be associated with microstructural damage of key fibre tracts, which could provide insights into the understanding and treatment of MDD.

Acupuncture for Major Depressive Disorder: A Data Mining-Based Literature Study.

Acupuncture has a long history of treating major depressive disorder (MDD), yet the acupoint selection of acupuncture for MDD varies greatly. This study aimed to explore the characteristics and principles of acupuncture for MDD by analyzing clinical trials of acupuncture for MDD using data mining techniques. In this study, clinical trials of acupuncture for MDD were retrieved and relevant data were extracted, and then the data were analyzed by data mining techniques. In addition, association rule mining, network analysis and hierarchical cluster analysis were used to determine the correlation between different acupoints. The results revealed that GV20, LR3, PC6, SP6 and GV29 were used most frequently; acupoints in the Yang meridian were used more often than those in the Yin meridian, with the most applied acupoints in the Governor Vessel; the percentage of specific acupoints applied was 69.39%, with the most applied being five-shu points; the frequency of acupoints used was highest in the lower limbs, while the head, face, and neck had the most acupoints used; GV29 combined with GV20 were the most used acupoint groups; the core acupoints used for MDD were GV20, PC6 and SP36; there were 5 acupoint groups according to the cluster analysis. The most used acupuncture method was manual acupuncture; the frequency of treatment was mostly 7 times per week and the duration of treatment was mostly 42 days. We discussed the current character of acupuncture treatment on MDD, including the frequency used of acupoints, the property of used acupoints, the acupoint combination, the acupuncture method, and the frequency and duration of treatment. These findings may provide new ideas for the clinical treatment of MDD. However, further clinical/experimental studies are needed to demonstrate the significance of this concept and approach.