Depressed Patients Research Articles

MicroRNA-specific targets for neuronal plasticity, neurotransmitters, neurotrophic factors, and gut microbes in the pathogenesis and therapeutics of depression

Depression is of great concern because of the huge burden, and it is impacted by various epigenetic modifications, e.g., histone modification, covalent modifications in DNA, and silencing mechanisms of non-coding protein genes, e.g., microRNAs (miRNAs). MiRNAs are a class of endogenous non-coding RNAs. Alternations in specific miRNAs have been observed both in depressive patients and experimental animals. Also, miRNAs are highly expressed in the central nervous system and can be delivered to different tissues via tissue-specific exosomes. However, the mechanism of miRNAs' involvement in the pathological process of depression is not well understood. Therefore, we summarized and discussed the role of miRNAs in depression. Conclusively, miRNAs are involved in the pathology of depression by causing structural and functional changes in synapses, mediating neuronal regeneration, differentiation, and apoptosis, regulating the gut microbes and the expression of various neurotransmitters and BDNF, and mediating inflammatory and immune responses. Moreover, miRNAs can predict the efficacy of antidepressant medications and explain the mechanism of action of antidepressant drugs and aerobic exercise to prevent and assist in treating depression.

Identification of Potential Diagnostic Markers for Depressive Disorders using Urinary Biomarkers of N-Methylnicotinamide and Hippuric Acid

Introduction: The diagnostic methodology for depressive disorders, relying on symptom clusters, has inherent limitations in ensuring heterogeneity levels. Consequently, this presents a notable risk of inevitable diagnostic errors in mental health assessments. Therefore, advocating for objective diagnostic approaches through empirical testing in clinical settings becomes crucial for individuals dealing with depressive disorders. This study aims to identify the effectiveness of urine as a diagnostic support for depressive disorders using the N-Methylnicotinamide and Hippuric Acid biomarkers. Methods: This study used 13 urine samples from patients with depressive disorders and 13 normal urine samples. It used ELISA methods with observational analytic and cross-sectional designs. Results: The results showed that the N-methylnicotinamide biomarker had a relationship with depressive disorders with a correlation value of 0.867, while hippuric acid obtained a correlation value of 0.692. Besides, the N-Methylnicotinamide and Hippuric Acid biomarkers showed differences in the urine of depressive disorder and normal patients with significance values of 0.000 and 0.001 for the N-Methylnicotinamide and Hippuric Acid biomarkers, respectively. In addition, the Relative Operating Characteristics curve analysis showed that these two biomarkers had good sensitivity and specificity values in assisting the diagnosis of depressive disorders. N-methylnicotinamide has a sensitivity of 92.3% and a specificity of 100%, while hippuric acid has a sensitivity of 76.9% and a specificity of 84.6%. Conclusions: Significant differences in the biomarkers of N-methylnicotinamide and hippuric acid in the urine of depressed patients compared to normal patients. Therefore, these biomarkers can be the empirical laboratory methods to support the diagnosis of depressive.

Effectiveness of 8-week TReatment with vortioxetine on depressive symptoms in major depressive disorder patients with comorbid generalized anxiety disorder in UAE (TRUE)

BackgroundMajor Depressive Disorder (MDD) is a leading cause of disability and results in excessive utilization of healthcare resources worldwide. The Middle East and North Africa (MENA) region shows a high prevalence of depressive disorders. Generalized Anxiety Disorder (GAD) and MDD have the highest rate of comorbidity of all mood and anxiety disorders, ranging from 40 to 98% in drug studies. Comorbid GAD results in more significant impairment in MDD and increases the severity of symptoms. Although several clinical trials supported the safety and effectiveness of vortioxetine, no data regarding these aspects has been revealed in the MENA region. This study aimed to assess the safety and efficacy of vortioxetine in patients with comorbid GAD in the United Arab Emirates (UAE).MethodIn a multicenter observational study, 118 patients with confirmed anxiety and depressive disorders were evaluated over four visits (baseline visit, two weeks, four weeks, and eight weeks) using MADRS and HAM-A scales to assess depression and anxiety severity, respectively by calculating mean change and the percent using Kendall’s W test.ResultsA significant mean difference in MADRS score was observed, with a gradual decrease of mean MADRS total scores over the assessment weeks (p < 0.001) as well as in HAM-A scores, from severe to moderate-severe anxiety through the four visits (p < 0.001). Furthermore, only one case was reported as a serious side effect. Nausea and insomnia were the most predominant side effects reported among the studied population.ConclusionVortioxetine was found effective and safe among patients with MDD and comorbid GAD.

Novel multi-layered MXene as laser desorption ionization mass spectrometry matrix for rapid detection of small biomolecules

Five two-dimensional multi-layered MXenes namely MO2C, Ti2C, V2C, Nb2C and Ta2C were synthesized by a one-step exfoliation process and evaluated as laser desorption ionization mass spectrometry (LDI-MS) matrices for fast detection of small biomolecules for the first time. Among them, Nb2C exhibited the best performance due to its high carrier mobility, strong photo-induced charge transfer resonance and good UV absorption ability. A simple, universal and efficient LDI-MS platform was established for small biomolecule analysis based on the Nb2C matrix. Key factors that affect LDI-MS efficacy were investigated and the established method demonstrated ultraclean MS background, high sensitivity with detection limits low to fmol level and good reproducibility. The Nb2C-based LDI-MS platform was successfully applied in the rapid determination of 13 amino acids (AAs) in human serum and 3 AAs, as potential biomarkers, were found to be significantly down-regulated in major depressive disorder patients. This work proved the feasibility of Nb2C MXene as an LDI-MS matrix and provided a promising and universal platform for the rapid detection of small molecules in biomedical research.

Safety and efficacy of individual target transcranial magnetic stimulation to stimulate the most negative correlate of DLPFC-pgACC in the treatment of major depressive disorder: study protocol of a double-blind, randomised controlled trial

IntroductionMajor depressive disorder (MDD) is a common mental disorder that is characterised by high morbidity, high rates of relapse, high rates of disability and, in severe cases, suicide ideas or...

Characteristics of Severe Late-Life Depression in the Prodromal Phase of Neurodegenerative Dementia

ObjectiveLate-life depression (LLD) is associated with neurodegenerative disease. The clinical characteristics of patients with LLD who develop neurodegenerative dementia or mild cognitive impairment (MCI) have not been thoroughly investigated. There has also been evidence that the severity of depression affects the transition to dementia. However, the clinical characteristics of the most severely depressed patients who receive the electroconvulsive therapy (ECT) and subsequently transition to a diagnosis of neurodegenerative disease remain unclear. MethodWe conducted a retrospective chart review of patients who received ECT between April 2012 and September 2022 at our academic hospital. We compared the clinical characteristics of individuals who transitioned to a diagnosis of neurodegenerative diseases and those whose diagnoses remained stable over a follow-up period of more than one year. ResultsOf the 94 patients who underwent ECT, 12 (13%) were diagnosed with neurodegenerative disease 20 months after their last ECT session. These patients had an older age of onset (p = 0.01) , fewer melancholic features (p = 0.03) , and fewer family histories of psychiatric disorders (p = 0.01) than those whose diagnoses did not change. ConclusionsIt is clinically important to consider the potential transition of older individuals with severe depression to neurodegenerative dementia or MCI, especially in cases characterized by an older age of onset, lack of melancholic features, or absence of a family history of psychiatric disorders.

Disruptions in segregation mechanisms in fMRI-based brain functional network predict the major depressive disorder condition

This study investigates the functional brain network in major depressive disorder using network theory and a consensus network approach. At the macroscopic level, we found significant differences in connectivity measures such as node strength and clustering coefficient, with healthy controls exhibiting higher values. This is consistent with disruptions in functional brain network segregation in patients with major depressive disorder. Consensus network analysis revealed that the central executive and salience networks were predominant in healthy controls, whereas depressed patients showed greater overlap with the default mode network. No differences were found in network efficiency measures, indicating comparable brain network integration between healthy controls and major depressive disorder groups. Importantly, the clustering coefficient emerged as an effective diagnostic biomarker for depression, achieving high sensitivity (90%), specificity (92%), and overall precision (90%). Further analysis at the mesoscale level uncovered unique functional connections distinguishing healthy controls and major depressive disorder groups. Our findings underscore the utility of analyzing functional networks from the macroscale to the mesoscale, and provide insight into overcoming the challenges associated with intersubject variability and the multiple comparisons problem in network analysis.

Anxiety and Depression Among Patients with Diabetes in Saudi Arabia and Egypt.

Mental stress plagued type II diabetes (T2DM) patients. The psychological and emotional issues related to diabetes and its effects include depression, anxiety, poor diet, and hypoglycemia fear. Compare the impact of diabetes on depression and anxiety in Egyptian and Saudi diabetics. The diabetes, gastroenterology, and hepatology sections of University of Ha'il Clinic, KSA, and the Theodor Bilharz Research Institute, Egypt, conducted this retrospective study. Everyone gave informed consent before participating. Interviews with male and female outpatients and inpatients were conducted from June 2021 to December 2022. The self-administered validated Generalized Anxiety Disorder-7 (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9) scale measured sociodemographic characteristics and symptoms of depression and anxiety. In patients with diabetes, the prevalence of depression was higher in KSA [34.8%] than in Egypt [18%], while anxiety was higher in Egypt [40%] than in KSA [29.1%]. Most depressed patients were 31-55 years old (61.2%) from KSA and 97.8% (41-55 years old) from Egypt. Female anxiety was 70.7% in KSA and 51.0% in Egypt, with no significant difference. The duration of diabetes in depressed patients was 5-10 years ([46.9%, Saudis] vs. [57.8%, Egyptians]), while anxious patients (5-10 years [39.0%, Saudis] vs. >20 years [65.0%, Egyptians]) were mainly type-2. Most depressive patients had an HbA1c (59.2%) from 7-10% (Saudis) and 77.8% [>10% Egyptians] compared to anxiety patients (46.3%) and 48.0% [>10% Egyptians]. Depressed and anxious patients from both nations had higher glucose, triglycerides, and cholesterol levels. Saudis and Egyptians with obesity had higher rates of sadness (75.5% vs. 68.9%) and anxiety (82.9% vs. 69.0%). Treatment adherence and serum glucose monitoring were not significantly different from depression in diabetes individuals in both ethnicities. Anxiety was more common among Egyptian patients because of overcrowding, working whole days to fulfill life requirements, and the unavailability of health insurance to all citizens. Meanwhile, in KSA, obesity, unhealthy food, and less exercise reflect the high percentage of depression among patients with diabetes. The detection of depression and anxiety in the context of DM should be critical for the physical health and quality of life of Saudi and Egyptian diabetics. Further investigation is warranted to encompass anxiety and depression within the scope of future research.

Plasma Brain-Derived Neurotrophic Factor (BDNF) Levels and BDNF Promoters’ DNA Methylation in Workers Exposed to Occupational Stress and Suffering from Psychiatric Disorders

Introduction: Decreased plasma BDNF (pBDNF) levels have been proposed as a biomarker in the illness phases of mood disorders. This cross-sectional study aimed to evaluate the pBDNF and BDNF promoters’ DNA methylation levels in workers exposed to occupational stress and suffering from work-related stress disorders. Methods: the pBDNF and BDNF exon I and IV promoters’ methylation levels were measured by specific immunoassays and methylation-sensitive high-resolution melting (MS-HRM) in 62 patients with adjustment disorders (AD), 79 patients with major depressive disorder (MDD) and 44 healthy controls. Occupational stress was evaluated in the patients and controls using the Job Content Questionnaire (JCQ). Results: the pBDNF levels were significantly higher in the MDD (p &lt; 0.001) and AD (p &lt; 0.0001) patients than in the controls. The MDD patients showed significantly lower pBDNF levels than the AD ones (p = 0.01). The BDNF exon I and IV promoters’ methylation levels were significantly higher in the MDD patients than in the AD ones (exon I promoter: p = 0.0001, exon IV promoter: p &lt; 0.0001) and controls (exon I promoter: p = 0.0001, exon IV promoter: p &lt; 0.0001). In the patients, but not in the controls, the BDNF promoters’ methylation levels showed significant negative correlations with occupational stress. Conclusions: BDNF could play a key role in the pathophysiology of stress-related disorders and the peripheral elevation of it observed in patients exposed to occupational stress could suggest a protective mechanism for neurons from stress-mediated damage. The elevation of the pBDNF levels, even in MDD, may characterize a “reactive” subtype of depressive episode, while the significant elevation of the BDNF promoters’ methylation levels in depressed patients could indicate a predisposition to more severe illness under stress. Further research is needed, focusing on biomarkers for stress-related disorders as a potential tool for the diagnosis and prevention of occupational diseases.

Joint effects of depression and social determinants of health on mortality risk among U.S. adults: a cohort study

BackgroundUnfavorable social determinants of health (SDoH) are associated with depression. Both depression and SDoH are associated with increased risks of mortality, but their joint impacts on mortality risks remain unclear. This study aims to investigate the joint effects of depression and SDoH on mortality risk.MethodsUtilizing data from the National Health and Nutrition Examination Survey (NHANES) 2007–2018, 24,727 adults aged ≥ 20 were included. SDoH was assessed based on the 5 domains outlined in the U.S. Healthy People 2030 initiative. The cumulative number of unfavorable SDoH was calculated and categorized into low and high burden levels. The definition of depression was based on the Patient Health Questionnaire-9 (PHQ-9) scores ≥ 10. The joint associations of depression and SDoH with all-cause, cardiovascular disease (CVD), and cancer mortality were examined using Cox proportional hazard models.ResultsWe identified 2,377 (6.84%) all-cause deaths (CVD, 717; cancer, 606) during a median follow-up of 7.0 years. Depression was associated with increased mortality risks, and SDoH could explain 32.4% and 28.3% of the associations between depression and all-cause and CVD mortality, respectively. No significant interactions were observed between depression and SDoH on mortality. However, a low burden of unfavorable SDoH reduced the risk of all-cause mortality in depressed patients (hazard ratio [HR], 0.58; 95% confidence interval [CI]: 0.36–0.92). In the joint analysis, individuals with both depression and a high burden of unfavorable SDoH had the highest risks of all-cause and CVD mortality. Specifically, compared with individuals with no depression and a low burden of unfavorable SDoH, those with depression and a high burden of unfavorable SDoH had higher risks of all-cause (HR, 2.52; 95% CI: 2.01–3.18) and CVD mortality (HR, 2.79; 95% CI: 1.95–3.99).ConclusionAdults with both depression and a high burden of unfavorable SDoH had the highest risks of all-cause mortality and CVD mortality. The result suggests considering depression and SDoH jointly in developing targeted intervention strategies to improve survival outcomes and calls for larger cohort studies and clinical trials to validate our findings.

Interplay between Stressful Life Events and Interleukin-1β on 12-week Antidepressant Response in Depressive Patients

Interplay between Stressful Life Events and Interleukin-1β on 12-week Antidepressant Response in Depressive Patients

The Efficacy of Omega-3 Fatty Acids as the Monotherapy for Depression: A Randomized, Double-Blind, Placebo-Controlled Pilot Study.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have demonstrated protective effects in major depressive disorder (MDD) patients receiving antidepressant treatment. However, there have been a few double-blind randomized controlled trials focused on n-3 PUFAs as monotherapy in MDD, and the outcomes have been mixed. This study aimed to assess the clinical effects of n-3 PUFAs monotherapy in patients with MDD. A total of 60 patients with MDD participated in this 12-week double-blind randomized controlled trial. They were randomized to either the n-3 PUFAs group (n = 30; 3.2 g of eicosapentaenoic acid, EPA and docosahexaenoic acid, DHA per day) or the placebo group (n = 30; 3.2 g of soybean oil per day). The severity of depression was evaluated using the Hamilton Rating Scale for Depression (HRSD). The n-3 PUFAs group had a significantly lower HRSD score compared with the placebo group at week 4 (p = 0.004), week 6 (p = 0.006), week 8 (p = 0.004), and week 12 (p = 0.01). The n-3 PUFAs group showed slightly higher rates for both remission (26.7% vs. 10%, p = 0.095) and response (23.3% vs. 6.7%, p = 0.145) compared with the placebo group at week 12, but these differences did not reach statistical significance. These findings suggested that monotherapy of n-3 PUFAs could improve depression and potentially serve as an alternative option for MDD patients.

Measuring social environment factors of depressed inpatients: A cross-sectional study

Abstract The course and management of mental illness are both influenced by social contextual factors. Standardised questionnaires are required to monitor inpatients’ social environment and to design interventions. This study aims to describe the social environment of inpatients with depression using standardised instruments, and to analyse the instrument’s applicability. This cross-sectional study included depressed adult inpatients admitted to a German psychiatric hospital. We used three standardised questionnaires to evaluate social risk factors: the Lubben Social Network Scale (LSNS), the WHO Disability Assessment Schedule (WHODAS) and the Social Cohesion and Trust Scale (SCTS). The appropriateness of the questionnaires was assessed with a context-specific quality appraisal. Our study included 196 patients with depression having a mean age of 38.8 (SD = 13.7) years of whom 50% were female. A total of 164 (85%) of patients reported a family history of mental health problems, and 31 (38.8%) had experienced discrimination. Analyses of the LSNS and WHODAS showed that the prevalence of social isolation and disability was significantly higher among inpatients compared to the general population. The WHODAS scores were highest in patients aged 18-30, while social isolation was elevated but stable among different age groups (range 18.7- 19.4%). Both, the WHODAS and LSNS showed good clinical applicability, comparability, and test properties. A lack of validation in a young population of the LSNS was considered a weakness. The SCTS showed imperfections in its applicability and comparability. Depressed inpatients have a limited social network compared to the general population. We emphasise the importance of assessing the applicability of questionnaires representing social environment as the basis for developing interventions. We recommend systematic monitoring of social characteristics to identify potential targets of intervention and thereby facilitate the management of depression. Key messages • Hospitalised patients with depression have a decreased social functioning and a smaller social network compared to the general population. • Standardised social environment questionnaires should be consented and used to plan and enrich depression management.

Running therapy or antidepressants as treatments for immunometabolic depression in patients with depressive and anxiety disorders: A secondary analysis of the MOTAR study

BackgroundExercise promotes immunometabolic health and is increasingly recognized as an effective depression treatment. Exercise may be beneficial for patients with immunometabolic depression (IMD), who experience inflammatory and metabolic dysregulations and may respond less to antidepressants. This secondary analysis of the MOTAR study compared the effects of running therapy and antidepressants on IMD features among patients with depression and/or anxiety disorder. We additionally assessed whether baseline IMD moderated intervention effects on depression. MethodsParticipants received 16 weeks of group-based running therapy (N = 96) or escitalopram/sertraline (N = 45) in a partially randomized patient preference design. IMD features included atypical, energy-related symptom (AES) severity, inflammation index (CRP, IFN-γ, IL-6, TNF-α), metabolic syndrome index, three metabolite principle components (PC) (derived from 73 metabolites) and a composite IMD index. ResultsInterventions differed in changes in the metabolic syndrome index (d = 0.59, p = 0.026) and IMD index (d = 0.85, p < 0.001). While running therapy decreased both outcomes, the antidepressant group showed an increased IMD index. Although groups did not differ statistically significant in changes in AES severity, inflammation index, and metabolite PC1, results indicated a consistent trend towards greater improvement with running therapy across these outcomes as well (d = 0.38 to 0.52). Baseline IMD did not moderate intervention effects on depression outcomes. ConclusionsThis study suggests that exercise more effectively targets the IMD dimension than antidepressants. Patients with IMD did not benefit more from running therapy than antidepressants in terms of reductions in depression. Exercise should be considered an alternative or complementary treatment to particularly reduce IMD features in depressed patients. Trial registrationTrialregister.nl Number of identification: NTR3460.

Association of the GRIK4 rs1954787 polymorphism with clinical response in antidepressant-treated depressed patients: results from a prospective cohort and meta-analysis.

Major Depressive Disorder (MDD) is the leading cause of disability worldwide. Genetic factors influence the effect of its main treatment option, antidepressant drugs (ATD). The GRIK4 rs1954787(T>C) genetic polymorphism was associated with response following 1-3 months of ATD treatment in some studies, but not others. We aimed to analyze its association with clinical outcomes in a cohort of 6-month ATD-treated patients and meta-analysis. Clinical data were obtained at baseline and after 1 (M1), 3 (M3), and 6 (M6) months of ATD treatment in 390 patients of the METADAP cohort. Mixed-effects models were used to assess the association of the GRIK4 rs1954787 polymorphism with the Hamilton Depression Rating Scale (HDRS) score and response and remission rates across time. Meta-analyses of ATD treatment response were performed with previously meta-analyzed data and METADAP. Compared to C allele carriers at M3 (n = 200), TT homozygotes at M3 (n = 66) had higher HDRS scores (coef = 3.37, 95% CI [1.30-5.54], Padj = 0.0046) and lower remission rates (OR = 0.36, 95% CI [0.16-0.76], Padj = 0.029). At M6, greater differences between TT homozygotes (n = 53) and C allele carriers (n = 152) were observed for HDRS scores (coef = 4.68, 95% CI [2.17-7.18], Padj = 0.00091) and remission rates (OR = 0.26, 95% CI [0.12-0.54], Padj = 0.0016). Meta-analyses of response were significant when comparing C vs T alleles (OR = 1.31, 95% CI [1.06-1.62], P = 0.014) and CC vs TT genotypes (OR = 1.63, 95% CI [1.10-2.38], P = 0.019). Altogether, our results support an association of the GRIK4 rs1954787(T>C) polymorphism with clinical improvement following ATD treatment. This association should be further assessed in other longitudinal studies. Its position within the glutamatergic system may help in understanding the mechanism of ATD action.

Heart rate variability and insomnia in depressed patients with breast cancer

ObjectivesDepression is associated with unhealthy autonomic regulation. However, whether patients with breast cancer (BC) with different degrees of depression can be identified from linear and non-linear dynamics in the autonomic...

The role of gender factors influencing multiple dimensions of somatic symptoms in major depressive disorder patients with suicidal ideation: insights from the Chinese NSSD study

BackgroundThe study aimed to explore the influence of gender on the prevalence of various somatic symptoms and their associations with suicidal ideation (SI) among patients with major depressive disorder (MDD).MethodsWe recruited 3,275 patients with MDD from the National Survey on Symptomatology of Depression (NSSD), among whom 1,745 patients had SI. The clinical characteristics and the prevalence of somatic symptoms across 20 dimensions in MDD patients with SI were compared between male and female patients. Spearman correlation analysis and logistic regression analysis were used to explore the relationship between somatic symptoms and SI.ResultsIn patients with SI, 32.2% of female participants attributed the onset of MDD to physical concerns, whereas 27% of male patients held a similar perspective (P = 0.032). Female patients exhibited a higher prevalence of early insomnia (64.6% vs. 70.2%) and a lower prevalence of hypersomnia (17.2% vs. 12.9%) and urinary system symptoms (25.0% vs. 17.8%). Logistic regression analysis indicated that female patients displayed a broader range of somatic symptoms identified as risk factors for SI, including increased appetite, respiratory symptoms, circulatory system symptoms, limb pain, and various others.ConclusionThis study unveils gender-specific patterns in somatic symptoms among MDD patients with SI, highlighting the clinical significance of these symptoms in diagnosis and intervention. Understanding how physical concerns contribute to MDD, especially among females, underscores the need for tailored clinical approaches. Recognizing and addressing these symptoms could guide more effective suicide prevention strategies and enhance MDD management in clinical practice.

Different dorsolateral prefrontal activation during an emotionalautobiographical memory task between male and female depressed individuals: a fNIRS study.

Depression in male and female are commonly associated with different prevalence, severity, and, in some cases, distinct syndromes or subtypes. However, only a small amount of research has been conducted to completely understand the underlying neuroanatomical mechanisms. The goal of the current study was to provide neural markers for specific depression therapies by demonstrating the differences in aberrant prefrontal activity between male and female depressed subjects during an emotional autobiographical memory test. The study included 127 young adults who were randomly assigned to one of two groups: male depression (62 participants) or female depression (65 participants). The average oxyhemoglobin levels in the dorsolateral prefrontal cortex throughout the emotional autobiographical memory task were assessed utilizing 53-channel functional near-infrared spectroscopy imaging equipment. The oxy-Hb activation in the left dorsolateral prefrontal cortex (lDLPFC) and right dorsolateral prefrontal cortex (rDLPFC) had no significant interaction between groups and emotional valences. A significant main effect was found between male and female, with female depression groups showing lower oxy-Hb activity in lDLPFC and rDLPFC than male depression groups. Male and female depression patients showed distinct brain activation in the DLPFC during an emotional autobiographical memory test, suggesting potential specific neurological indicators for varied somatic symptoms in male and female depression patients. These distinctions should be taken into account while creating preventive measures.

Extended course accelerated intermittent theta burst stimulation as a substitute for depressed patients needing electroconvulsive therapy.

In response to restrictions on electroconvulsive therapy (ECT) access during COVID-19, we designed a trial to assess the clinical outcomes service impacts, employing an extended course of accelerated intermittent theta burst stimulation (aiTBS), in patients with moderate to severe depression in need of ECT. This open label clinical trial was comprised of 3 phases: (i) an acute phase, where iTBS treatments were administered 8 times daily, for up to 10 days; (ii) a tapering phase of 2 treatment days per week for 2 weeks, followed by 1 treatment day per week for 2 weeks; and (iii) a symptom-based relapse prevention phase, whereby treatments were scheduled based on symptom re-emergence, for up to 6 months. Of the 155 patients who completed the acute phase of the study, the remission rate was 16.1%. The mean reduction from baseline on the HRSD-24 was 29.4% (p < 0.001) and the response rate was 25.2%. Of the 110 patients who completed the tapering phase, the mean reduction from baseline was 42.6% (p < 0.001) and response and remission rates were 49.6% and 34.8%, respectively. Of the 61 patients who were eligible for the relapse prevention phase, 43 completed, with a mean reduction from baseline of 60.1% (p < 0.001); 7 patients relapsed during this phase. This study demonstrated that an extended aiTBS protocol safely led to meaningful clinical outcomes in patients with severe depression, who otherwise would have received ECT, and thus reduced pressure on ECT services during the pandemic. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04384965 ( https://clinicaltrials.gov/study/NCT04384965?term=NCT04384965&rank=1 ).

Comorbidity, Treatment, and Service Utilization Patterns in Difficult-to-Treat Depression Patients: A Retrospective Study in a Portuguese Community Mental Health Team

Background and Objectives: Observational studies with data from real-world clinical practice with patients with difficult-to-treat depression (DTD) are rare. This study aims to collect observational data from the real-world clinical practice of a Portuguese community mental health team (CMHT) on the prevalence of DTD and to explore differences between DTD and non-DTD groups. Materials and Methods: We conducted a retrospective chart review study using data from Electronic Health Records (EHRs) of adult patients with psychiatric disorders followed by a CMHT from the Department of Psychiatry of the Coimbra Local Health Unit (between 1 December 2020–31 December 2022). The Dutch Measure for quantification of Treatment Resistance in Depression (DM-TRD) was used to assess the degree of treatment resistance and the Charlson Comorbidity Index (CCI) to measure medical comorbidity. Results: A quantity of 473 patients were referred to Cantanhede CMHT for a first assessment. Of these, 219 patients met the criteria for a primary diagnosis of any depressive disorder. Assistant psychiatrists identified 57 patients with DTD during follow-up (approximately 26%). The DTD group had higher rates of depressive episodes, greater depression severity, increased service use, higher DM-TRD scores, and a higher prevalence of comorbid anxiety symptoms, personality disorders, and severe medical comorbidities. The DTD group also had a higher prescription rate of antidepressants. Differences were observed in the use of antidepressant augmentation strategies and in the prescription of anticoagulant/antiplatelet drugs and analgesics, with higher prescription rates in the DTD group. We found correlations between DM-TRD and CCI scores, and between DM-TRD scores and all service use variables. Conclusions: Our results are consistent with a similar study in the United Kingdom, highlighting the need for a different approach to the management of DTD patients, who continue to live with a significant burden despite usual pharmacological and non-pharmacological treatments.