Remission Of Depressive Symptoms Research Articles

Cost-Effectiveness of Digital Mental Health Versus Usual Care During Humanitarian Crises in Lebanon: Pragmatic Randomized Trial

Background There is evidence from meta-analyses and systematic reviews that digital mental health interventions for depression, anxiety, and stress-related disorders tend to be cost-effective. However, no such evidence exists for guided digital mental health care in low and middle-income countries (LMICs) facing humanitarian crises, where the needs are highest. Step-by-Step (SbS), a digital mental health intervention for depression, anxiety, and stress-related disorders, proved to be effective for Lebanese citizens and war-affected Syrians residing in Lebanon. Assessing the cost-effectiveness of SbS is crucial because Lebanon’s overstretched health care system must prioritize cost-effective treatment options in the face of continuing humanitarian and economic crises. Objective This study aims to assess the cost-effectiveness of SbS in a randomized comparison with enhanced usual care (EUC). Methods The cost-effectiveness analysis was conducted alongside a pragmatic randomized controlled trial in 2 parallel groups comparing SbS (n=614) with EUC (n=635). The primary outcome was cost (in US $ for the reference year 2019) per treatment response of depressive symptoms, defined as >50% reduction of depressive symptoms measured using the Patient Health Questionnaire (PHQ). The secondary outcome was cost per remission of depressive symptoms, defined as a PHQ score <5 at last follow-up (5 months post baseline). The evaluation was conducted first from the health care perspective then from the societal perspective. Results Taking the health care perspective, SbS had an 80% probability to be regarded as cost-effective compared with EUC when there is a willingness to pay US $220 per additional treatment response or US $840 per additional remission. Taking the wider societal perspective, SbS had a >75% probability to be cost-saving while gaining response or remission. Conclusions To our knowledge, this study is the first cost-effectiveness analysis based on a large randomized controlled trial (n=1249) of a guided digital mental health intervention in an LMIC. From the principal findings, 2 implications flowed, from the (1) health care perspective and (2) wider societal perspective. First, our findings suggest that SbS is associated with greater health benefits, albeit for higher costs than EUC. It is up to decision makers in health care to decide if they find the balance between additional health gains and additional health care costs acceptable. Second, as seen from the wider societal perspective, there is a substantial likelihood that SbS is not costing more than EUC but is associated with cost-savings as SBS participants become more productive, thus offsetting their health care costs. This finding may suggest to policy makers that it is in the interest of both population health and the wider Lebanese economy to implement SbS on a wide scale. In brief, SbS may offer a scalable, potentially cost-saving response to humanitarian emergencies in an LMIC. Trial Registration ClinicalTrials.gov NCT03720769; https://clinicaltrials.gov/ct2/show/NCT03720769 International Registered Report Identifier (IRRID) RR2-10.2196/21585

Technical Report: Efficacy and Safety of Low-Intensity Transcranial Magnetic Stimulation in the Remission of Depressive Symptoms in Patients With Treatment-Resistant Depression in Mexico

Technical Report: Efficacy and Safety of Low-Intensity Transcranial Magnetic Stimulation in the Remission of Depressive Symptoms in Patients With Treatment-Resistant Depression in Mexico

Collaborative Care for Depression and Anxiety: Racial-Ethnic Differences in Treatment Engagement and Outcomes.

This study aimed to examine racial-ethnic differences in engagement with and clinical outcomes of a collaborative care model (CoCM) implemented in primary care outpatient clinics in an urban academic medical center. Adult patients (N=4,911) who screened positive for symptoms of depression, anxiety, or both on the Patient Health Questionnaire-9 or the Generalized Anxiety Disorder-7 scale and who identified as non-Hispanic Black, Hispanic, or non-Hispanic White were offered participation in a CoCM implementation. The primary outcome was treatment engagement, defined as receipt of any follow-up visit, minimally adequate 4-week follow-up (at least one visit), and minimally adequate 16-week follow-up (at least three visits) after initial assessment. Secondary outcomes were response and remission of depression or anxiety. After adjustment of analyses for sociodemographic covariates, Black and Hispanic participants were significantly less likely than White participants to have received any or minimally adequate follow-up. Black and Hispanic participants who received any or minimally adequate 16-week follow-up were more likely than White participants to demonstrate depression symptom response and remission of anxiety symptoms. This CoCM implementation appears to have been effective in treating depression and anxiety among Black and Hispanic patients. However, significant disparities in receipt of follow-up care were observed. Efforts must be made to improve the retention of patients from racial-ethnic minority groups in collaborative care.

Serum neuroactive metabolites of the tryptophan pathway in patients with acute phase of affective disorders.

Many studies showed disrupted tryptophan metabolism in patients with affective disorders. The aims of this study were to explore the differences in the metabolites of tryptophan pathway (TP) and the relationships between TP metabolites and clinical symptoms, therapeutic effect in patients with bipolar disorder with acute manic episode (BD-M), depressive episode (BD-D) and major depressive disorder (MDD). Patients with BD-M (n=52) and BD-D (n=39), MDD (n=48) and healthy controls (HCs, n=49) were enrolled. The serum neuroactive metabolites levels of the TP were measured by liquid chromatography-tandem mass spectrometry. Hamilton Depression Scale-17 item (HAMD-17) and Young Mania Rating Scale (YMRS) were used to evaluate depressive and manic symptoms at baseline and after 8 weeks of antidepressants, mood stabilizers, some also received antipsychotic medication. The levels of tryptophan (TRP) and kynurenic acid (KYNA) were significantly lower and the ratios of tryptophan/kynurenine (TRP/KYN), 5-hydroxytryptamine/tryptophan (5-HT/TRP), quinolinic acid/kynurenic acid (QUIN/KYNA) were higher in BD-M, BD-D, MDD vs. HC. The levels of QUIN and the ratios of QUIN/KYNA were higher in BD-M than in BD-D, MDD, and HCs. The 5-hydroxyindoleacetic acid (5-HIAA) levels of patients with MDD were significantly higher than those in BD-M and BD-D. Binary logistic regression analysis showed the lower peripheral KYNA, the higher the QUIN level, and the higher the risk of BD-M; the lower peripheral KYNA and the higher KYN/TRP and 5-HT/TRP, the higher the risk of BD-D; and the lower the peripheral KYNA level and the higher the KYN/TRP and 5-HT/TRP, the higher the risk of MDD. Correlation analysis, showing a significant association between tryptophan metabolites and improvement of clinical symptoms, especially depression symptoms. Patients with affective disorders had abnormal tryptophan metabolism, which involved in 5-HT and kynurenine pathway (KP) sub-pathway. Tryptophan metabolites might be potential biomarkers for affective disorders and some metabolites have been associated with remission of depressive symptoms.

Adjunctive cariprazine for major depressive disorder: a systematic review and meta-analysis.

Converging evidence has suggested that treatment augmentation with a second-generation atypical antipsychotic (SGA) may improve treatment outcomes in major depressive disorder (MDD) patients after an incomplete response to a first-line antidepressant. Cariprazine is a recently approved SGA for MDD augmentation. Herein, we evaluate both continuous (ie, change in depressive symptom severity scores over time) and categorical (ie, remission and response rates) outcomes. Following a full-text review, four randomized controlled trials (RCTs) were included in our meta-analysis, while five studies were included for a qualitative review. Risk ratios (RRs) were calculated for all included randomized controlled studies to determine the relative response and remission rates of cariprazine compared to placebo augmentation. The RR for all-cause dropout was also determined as a proxy for overall acceptability. Two studies found a statistically significant treatment response using cariprazine augmentation. One study observed depressive symptom remission for cariprazine compared to placebo. Our random-effects model revealed moderate antidepressant effects of cariprazine, with a standardized mean difference (SMD) in Montgomery-Åsberg Depression Rating Scale (MADRS) scores of -1.79 (95% CI): -2.89, -0.69). Our pooled response RR and remission RR were calculated as 1.21 (95% CI: 1.05, 1.39, P=0.008) and 0.99 (95% CI: 0.84, 1.17, P=0.91), respectively. The RR for response was statistically significant (P<0.05). However, the RR for remission was not statistically significant. The findings from our meta-analysis include a variable magnitude of effects. Evidence suggests cariprazine may be an effective treatment for MDD; however, further results are needed to clarify this relation.

A real-world retrospective cohort study comparing two bilateral stimulation protocols of add-on rTMS in patients with treatment resistant depression and severe anxiety

BackgroundTranscranial magnetic stimulation (TMS) has been shown to improve response and remission in patients with treatment resistant depression. The objective of this study was to compare the efficacy of two bilateral rTMS protocols with different protocols in patients with treatment resistant depression and comorbid severe anxiety. MethodsA retrospective cohort study involving 67 patients who underwent two different bilateral TMS protocols and who met the specified eligibility criteria was conducted. Group 1 received stimulation with 85% RMT intermittent theta burst (iTBS) in the left DLPFC + 120% RMT (1 Hz) in the right DLPFC. Group 2 received stimulation with 100% RMT (iTBS) in the left DLPFC + 110% RMT (1 Hz) in the left DLPFC. ResultsAfter the magnetic stimulation treatment, 55% (n=22) achieved response to depression symptoms in group 1 and 62% (n=18) in group 2. Remission of depression symptoms was achieved in 13% in group 1 (n=5) and 24% in group 2 (n=7). There were no significant differences between the two protocols after TMS ConclusionsDifferent bilateral protocol parameters in individuals undergoing TMS may have an impact on symptom response and remission. Further studies with larger sample sizes are needed.

Longitudinal outcomes of a therapist-supported digital mental health intervention for depression and anxiety symptoms: A retrospective cohort study.

This study examined treatment outcomes (depression and anxiety symptoms) up to 24 months after completion of a therapist-supported digital mental health intervention (DMHI). The sample consisted of 380 participants who participated in an eight-week DMHI from February 6, 2017 to May 20, 2019. Participants reported depression and anxiety symptoms at eight timepoints from baseline to 24 months. Mixed-effects modelling was used to investigate symptom changes over time. The proportion of participants meeting criteria for treatment response, clinically significant change, and remission of depression and anxiety symptoms were calculated, including proportions demonstrating each outcome sustained up to each timepoint. Multivariate analyses yielded statistically significant reductions in depression (β = -5.40) and anxiety (β = -3.31) symptoms from baseline to end of treatment (8 weeks). Symptom levels remained significantly reduced from baseline through 24 months. The proportion of participants meeting criteria for clinical treatment outcomes remained constant over 24 months, although there were linear decreases in the proportions experiencing sustained clinical outcomes. Treatment gains were made for depression and anxiety symptoms at the end of treatment and up to 24 months. Future studies should determine the feasibility of integrating post-treatment programmes into DMHIs to address symptom deterioration.

Use of sertraline and agomelatine in hemodialysis patients: A case series report.

Major depressive disorder (MDD) is one of the most common psychiatric issues in hemodialysis population. However, the research on proper diagnostic tools and its treatment is still insufficient. The study was performed to investigate the safety and effectiveness of sertraline and agomelatine in a group of hemodialysis patients. 78 adult patients from one dialysis centre in Poland were included into the study. The Beck Depression Inventory II (BDI-II) was used to screen for depressive symptoms and was followed by the clinical interview with the psychiatrist. Nine patients diagnosed with major depressive disorder received antidepressant treatment with sertraline or agomelatine, according to the best clinical practice. The additional treatment with vortioxetine was used if the initial one was not effective. The time of observation was 24 weeks. The psychiatric follow up as well as the laboratory data were obtained during the course of observation. All patients receiving sertraline achieved remission of depressive symptoms. In patients receiving agomelatine no remission was observed despite dose augmentation. The side effects of antidepressants were mild and did not result in treatment discontinuation. No abnormalities in liver enzymes levels were observed. In five cases the significant decrease of haemoglobin level was noticed, with no cases of bleeding reported. In patients receiving sertraline the antidepressant effect was satisfactory. No remission of depressive symptoms was observed in patients taking agomelatine. The side effects of antidepressants were mild and transient. Further research on depression treatment in hemodialysis patients is needed, including newer medications.

Can cognitive inflexibility reduce symptoms of anxiety and depression? Promoting the structural nested mean model in psychotherapy research

ABSTRACT Objective To estimate the causal effect of executive functioning on the remission of depression and anxiety symptoms in an observational dataset from a vocational rehabilitation program. It is also an aim to promote a method from the causal inference literature and to illustrate its value in this setting. Method With longitudinal (four-time points over 13 months) data from four independent sites, we compiled a dataset with 390 participants. At each time point, participants were tested on executive function and self-reported symptoms of anxiety and depression. We used g-estimation to evaluate whether objectively tested cognitive flexibility affected depressive/anxious symptoms and tested for moderation. Multiple imputations were used to handle missing data. Results The g-estimation showed a strong causal effect of cognitive inflexibility reducing depression and anxiety and modified by education level. In a counterfactual framework, a hypothetical intervention that could lower cognitive flexibility seemed to cause improvement in mental distress at the subsequent time-point (negative sign) for low education. The less flexibility, the larger improvement. For high education, the same but weaker effect was found, with a change in sign, negative during the intervention and positive during follow-up. Discussion An unexpected and strong effect was found from cognitive inflexibility on symptom improvement. This study demonstrates how to estimate causal psychological effects with standard software in an observational dataset with substantial missing and shows the value of such methods.

Enhanced rich club connectivity in mild or moderate depression after nonpharmacological treatment: A preliminary study.

It has been suggested that the rich club organization in major depressive disorder (MDD) was altered. However, it remained unclear whether the rich club organization could be served as a biomarker that predicted the improvement of clinical symptoms in MDD. The current study included 29 mild or moderate patients with MDD, who were grouped into a treatment group (receiving cognitive behavioral therapy or real-time fMRI feedback treatment) and a no-treatment group. Resting-state MRI scans were obtained for all participants. Graph theory was employed to investigate the treatment-related changes in network properties and rich club organization. We found that patients in the treatment group had decreased depressive symptom scores and enhanced rich club connectivity following the nonpharmacological treatment. Moreover, the changes in rich club connectivity were significantly correlated with the changes in depressive symptom scores. In addition, the nonpharmacological treatment on patients with MDD increased functional connectivity mainly among the salience network, default mode network, frontoparietal network, and subcortical network. Patients in the no-treatment group did not show significant changes in depressive symptom scores and rich club organization. Those results suggested that the remission of depressive symptoms after nonpharmacological treatment in MDD patients was associated with the increased efficiency of global information processing.

Temporal Network of Depressive Symptoms across College Students with Distinct Depressive Trajectories during the COVID-19 Pandemic

Background. There are marked differences in how individuals respond and adapt to depressive symptoms over time during the strain of public health emergencies; however, few studies have examined the interrelations between depressive symptoms in distinct depressive trajectories from the COVID-19 outbreak period to the COVID-19 control period. Therefore, this study conducted cross-lagged panel networks to investigate the temporal relationships between depressive symptoms across distinct depressive trajectories from the COVID-19 outbreak period (T1) to the COVID-19 control period (T2). Methods. A total of 35,516 young participants from the College Students’ Behavior and Health Cohort during the COVID-19 pandemic were included in the current study. Depressive symptoms were self-reported using the nine-item Patient Health Questionnaire. Unique longitudinal relationships between symptoms during the COVID-19 pandemic were estimated using a cross-lagged panel network. Results. Longitudinal relationships across distinct depressive trajectories were unique during the COVID-19 pandemic. Specifically, suicidal ideation at T1 in the chronic- and delayed-dysfunction groups was most predictive of other symptoms at T2, whereas “sleep” at T1 in the recovery group and “lack of energy” at T1 in the resistance group may be strongly related to the remission of other depressive symptoms at T2. Conclusions. These exploratory findings demonstrate the directionality of relationships underlying individual symptoms in the youth and highlight suicidal ideation, sleep, and energy as potential influencers of other depressive symptoms across distinct depressive trajectories. Targeting those symptoms during the outbreak period of COVID 19 would theoretically have been beneficial in preventing and/or reducing the likelihood of spontaneous depression during the subsequent control period.

Longitudinal Patterns of Engagement and Clinical Outcomes: Results From a Therapist-Supported Digital Mental Health Intervention.

Digital mental health interventions (DMHIs) are an effective treatment modality for common mental disorders like depression and anxiety; however, the role of intervention engagement as a longitudinal "dosing" factor is poorly understood in relation to clinical outcomes. We studied 4978 participants in a 12-week therapist-supported DMHI (June 2020-December 2021), applying a longitudinal agglomerative hierarchical cluster analysis to the number of days per week of intervention engagement. The proportion of people demonstrating remission in depression and anxiety symptoms during the intervention was calculated for each cluster. Multivariable logistic regression models were fit to examine associations between the engagement clusters and symptom remission, adjusting for demographic and clinical characteristics. Based on clinical interpretability and stopping rules, four clusters were derived from the hierarchical cluster analysis (in descending order): a) sustained high engagers (45.0%), b) late disengagers (24.1%), c) early disengagers (22.5%), and d) immediate disengagers (8.4%). Bivariate and multivariate analyses supported a dose-response relationship between engagement and depression symptom remission, whereas the pattern was partially evident for anxiety symptom remission. In multivariable logistic regression models, older age groups, male participants, and Asians had increased odds of achieving depression and anxiety symptom remission, whereas higher odds of anxiety symptom remission were observed among gender-expansive individuals. Segmentation based on the frequency of engagement performs well in discerning timing of intervention disengagement and a dose-response relationship with clinical outcomes. The findings among the demographic subpopulations indicate that therapist-supported DMHIs may be effective in addressing mental health problems among patients who disproportionately experience stigma and structural barriers to care. Machine learning models can enable precision care by delineating how heterogeneous patterns of engagement over time relate to clinical outcomes. This empirical identification may help clinicians personalize and optimize interventions to prevent premature disengagement.

An interdisciplinary multimodal integrative healthcare program for depressive and anxiety disorders.

Although multimodal interventions are recommended in patients with severe depressive and/or anxiety disorders, available evidence is scarce. Therefore, the current study evaluates the effectiveness of an outpatient secondary care interdisciplinary multimodal integrative healthcare program, delivered within a transdiagnostic framework, for patients with (comorbid) depressive and/or anxiety disorders. Participants were 3,900 patients diagnosed with a depressive and/or anxiety disorder. The primary outcome was Health-Related Quality of Life (HRQoL) measured with the Research and Development-36 (RAND-36). Secondary outcomes included: (1) current psychological and physical symptoms measured with the Brief Symptom Inventory (BSI) and (2) symptoms of depression, anxiety, and stress measured with the Depression Anxiety Stress Scale (DASS). The healthcare program consisted of two active treatment phases: main 20-week program and a subsequent continuation-phase intervention (i.e., 12-month relapse prevention program). Mixed linear models were used to examine the effects of the healthcare program on primary/secondary outcomes over four time points: before start 20-week program (T0), halfway 20-week program (T1), end of 20-week program (T2) and end of 12-month relapse prevention program (T3). Results showed significant improvements from T0 to T2 for the primary variable (i.e., RAND-36) and secondary variables (i.e., BSI/DASS). During the 12-month relapse prevention program, further significant improvements were mainly observed for secondary variables (i.e., BSI/DASS) and to a lesser extent for the primary variable (i.e., RAND-36). At the end of the relapse prevention program (i.e., T3), 63% of patients achieved remission of depressive symptoms (i.e., DASS depression score ≤ 9) and 67% of patients achieved remission of anxiety symptoms (i.e., DASS anxiety score ≤ 7). An interdisciplinary multimodal integrative healthcare program, delivered within a transdiagnostic framework, seems effective for patients suffering from depressive and/or anxiety disorders with regard to HRQoL and symptoms of psychopathology. As reimbursement and funding for interdisciplinary multimodal interventions in this patient group has been under pressure in recent years, this study could add important evidence by reporting on routinely collected outcome data from a large patient group. Future studies should further investigate the long-term stability of treatment outcomes after interdisciplinary multimodal interventions for patients suffering from depressive and/or anxiety disorders.

665-P: Longitudinal Impact of Daily Experienced Diabetes Distress and Affective Symptoms on the Incidence and Remission of Depressive Symptoms—Results of the DIA-LINK 1 and 2 Studies

We analyzed whether daily experience of diabetes distress and affective symptoms, assessed with ecological momentary assessment (EMA) can predict incidence or remission of elevated depressive symptoms in people with type 1 and type 2 diabetes. In the DIA-LINK studies, 203 people with type 1 and 193 people with type 2 diabetes participated. In the 17-day EMA phase, participants completed daily prompts assessing different affective symptoms and diabetes distress. 358 participants completed the CES-Depression questionnaire at baseline and 3 months later. Incidence and remission of elevated depressive symptoms were defined by a cut-off score of 22. Area under receiver operating characteristics curves were used to analyse the predictive performance of EMA variables on incidence and remission of depressive symptoms. Incidence of elevated depressive symptoms was 18.3% while 32.3% showed a remission. Predictive performances of 15 different EMA variables are shown in Table 1. Daily experience of diabetes distress and affective symptoms can predict incidence and remission of elevated depressive symptoms. These variables could be used for designing just-in-time adaptive interventions for preventing elevated depressive symptoms in people with diabetes experiencing daily emotional burden of living with diabetes. Disclosure D.Ehrmann: Advisory Panel; Roche Diabetes Care, mySugr, Dexcom, Inc., Speaker's Bureau; Berlin-Chemie AG, Dexcom, Inc. A.J.Schmitt: None. B.Olesen: Advisory Panel; AstraZeneca, Evivamed, Berlin-Chemie AG, Speaker's Bureau; Medtronic, Medtrixx. B.Kulzer: Advisory Panel; Berlin-Chemie AG, Abbott Diabetes, Bayer Inc., Dexcom, Inc., Novo Nordisk, Insulet Corporation, embecta, Research Support; Sanofi, Roche Diabetes Care. N.Hermanns: Advisory Panel; Insulet Corporation, Research Support; Sanofi-Aventis Deutschland GmbH, Roche Diagnostics, Becton, Dickinson and Company, Speaker's Bureau; Dexcom, Inc., Berlin-Chemie AG. Funding German Center for Diabetes Research (FKZ82DZD1102A)

Long term efficacy of psilocybin in patients with cancer and major depressive disorder (MDD).

12021 Background: Up to 25% of people living with cancer have depression. Existing psychological interventions have limited efficacy in treating depression. Psilocybin, a 5-hydroytrptamintergic psychedelic, coupled with group therapy is safe and effective in ameliorating symptoms of depression (Agrawal et al, ASCO 2022). Response to psilocybin treatment was observed in 83.3% of patients at 8 weeks, and 50% of patients showed full remission of depressive symptoms. This study evaluates the efficacy of psilocybin-assisted group therapy in relieving depression in cancer patients over 18 months. Methods: Adults with curable or metastatic cancer and MDD (according to DSM-5) underwent psychological assessments at baseline. They were treated with single-dose psilocybin 25 mg administered simultaneously in group cohorts of 3-4, supported with group and individual psychological therapy, and evaluated at 8 weeks and 18 months. Primary objectives were long-term effectiveness on depression and anxiety severity (as measured by change in Montgomery Asberg Depression Rating Scale [MADRS] and Hamilton Depression Rating Scale [HAM-A] scores by independent rater assessments) as well as clinical response (≥50% decrease in MADRS total score from baseline to 18 months) and remission (defined as patients with a MADRS total score ≤10 at 18 months). Results: Of 30 patients enrolled in the parent study, 2 died and 4 were lost to follow-up. Clinical response was demonstrated in 18/28 patients (64.2%) from baseline to 18 months follow-up (see table); 16/28 patients (57.1%) demonstrated remission of depression at 18 months. In 24 evaluable patients, continued reduction in mean depression severity scores was also demonstrated from baseline to week 8 (MADRS by 20.6 points [95% CI 23.2, 18.0, p &lt; 0.001] and HAMA-A by 16.7 points [95% CI 19.7, 13.7, p &lt; 0.001]) and from baseline to 18 months (MADRS by 16.7 points [95% CI 20.4, 12.9, p &lt; 0.001] and HAMA-A by 14.4 points [95% CI 17.3, 11.4, p &lt; 0.001]). Conclusions: Long-term follow-up suggests continued robust clinical response and remission from depression with a single dose of psilocybin and simultaneous psychological support in patients with cancer and MDD. These findings indicate psilocybin may play a role in treatment of depression in cancer patients, and further investigations are ongoing. [Table: see text]

Difficult-To-Treat Depression. Scoping Review.

Recently, several academics have recommended that the concept of difficult-to-treat depression (DTD) should be considered in some of the cases where achieving or maintaining remission of depressive symptoms is not possible. In 2020, a consensus statement, not based on a formal process and systematic review defined difficult-to-treat depression as "depression that continues to cause significant burden despite normal treatment efforts". In addition to addressing symptom control, interventions for DTD should also target other factors, including the management of psychiatric and medical comorbidities, psychosocial functioning, self-esteem, and self-management strategies. The purpose of this scoping review is to explore the scientific literature, which is still unclear and vague, regarding the pathophysiology and treatment of difficult-to-treat depression, providing a summary of its current conceptualization. This represents a cultural and scientific shift that offers clinicians and researchers valid and up-to-date study criteria, thus expanding upon the model of treatment-resistant depression (TRD). Consequently contributions, concepts, theories and gaps of the state of the art in the description of difficult-to-treat depression have been summarized here. A research study was conducted using PubMed, Scopus, PsycINFO, Cochrane Library, and Open Grey databases to identify and examine articles reporting key features related to the recent concept of difficult-to-treat depression. The research covered a period of time between January 1, 2013, and March 1, 2023. Based on a formal checklist, two researchers independently assessed the eligibility criteria to determine which studies to include or exclude in this search. Further data evaluations were conducted for the articles that were deemed to have the most comprehensive descriptions. The results of the research yielded a body of literature that provides a clear definition of difficult-to-treat depression and insights into its clinical application and research perspective. DTD represents a cultural and scientific shift that provides clinicians and researchers with valid and up-to-date study criteria that allow the extension of the treatment-resistant depression (TRD) model. The main difference lies in the operational process of assessment and intervention in the depressive syndrome in relation to the search for a therapeutic response. The results of this review show that DTD is a theoretically and clinically useful conceptualization for depressive syndromes that are not just simply resistant to treatment. This clinical condition entails a novel clinical therapeutic approach for specific patients and may be used throughout the world to help recognize this clinical condition while optimizing overall care for these patients. However, as we have highlighted, in the absence of RCTs and further observational studies, it is desirable that DTD be further investigated and defined..

Bifrontal electroconvulsive therapy leads to improvement of cerebral glucose hypometabolism in frontotemporal dementia with comorbid psychotic depression – a case report

BackgroundDifferentiating depression and dementia in elderly patients represents a major clinical challenge for psychiatrists. Pharmacological and non-pharmacological treatment options for both conditions are often used cautiously due to fear of adverse effects. If a clinically indicated therapy is not initiated due to fear of adverse effects, the quality of life of affected patients may significantly be reduced.Case presentationHere, we describe the case of a 65-year-old woman who presented to the department of psychiatry of a university hospital with depressed mood, pronounced anxiety, and nihilistic thoughts. While several pharmacological treatments remained without clinical response, further behavioral observation in conjunction with 18F-fluoro‐2‐deoxy‐D‐glucose positron emission tomography/computed tomography (18F-FDG PET/CT) revealed the diagnosis of frontotemporal dementia (FTD). To counter the pharmacological treatment resistance of psychotic depression, we decided to perform electroconvulsive therapy (ECT). Remarkably, ten sessions of ECT yielded an almost complete remission of depressive symptoms. In addition, the patient’s delusional ideas disappeared. A follow-up 18F-FDG PET/CT after the ECT series still showed a frontally and parieto-temporally accentuated hypometabolism, albeit with a clear regression compared to the previous image. The follow-up 18F-FDG PET/CT thus corroborated the diagnosis of FTD, while on the other hand it demonstrated the success of ECT.ConclusionsIn this case, ECT was a beneficial treatment option for depressive symptoms in FTD. Also, 18F-FDG PET/CT should be discussed as a valuable tool in differentiating depression and dementia and as an indicator of treatment response.

Selecting Antidepressants Based on Medical History and Stress Mechanism.

Purpose At present, clinicians typically prescribe antidepressants based on the widely accepted "serotonin hypothesis."This study explores an alternative mechanism, the stress mechanism, for selecting antidepressants based on patients' medical history. Methods This study investigated clinicians' prescribing patterns for the 15 most common antidepressants, including amitriptyline, bupropion, citalopram, desvenlafaxine, doxepin, duloxetine, escitalopram, fluoxetine, mirtazapine, nortriptyline, paroxetine, ropinirole, sertraline, trazodone, and Venlafaxine. The least absolute shrinkage and selection operator (LASSO) logistic regression was used to identify factors that affect the remission of depression symptoms after receiving an antidepressant. Results The study found that a wide range of factors influenced the propensity of clinicians to prescribe antidepressants, with the number of predictors ranging from 51 to 206 variables. The prevalence of prescribing an antidepressant ranged from 0.5%for doxepin to 24% for the combinationof more than one antidepressant. The area under the receiver operating curves (AROC) ranged from 77.2% for venlafaxine to 90.5% for ropinirole, with an average AROC of 82% for predicting the propensity of medications. A variety of diagnoses and prior medications affected remission, in agreement that the central mechanism for the impact of medications on the brain is through stress reduction. For example, psychotherapy, whether done individually or in a group, whether done for a short or long time, and whether done with evaluation/assessment or not, had an impact on remission.Specifically, teenagers and octogenarians were less likely to benefit from bupropion, citalopram, escitalopram, fluoxetine, and sertraline compared to patients between 40 and 65 years old.The findings of this study suggest that considering a patient's medical history and individual characteristics is crucial for selecting the most effective antidepressant treatment. Conclusions Many studies have raised doubt about the serotonin hypothesis as the central mechanism for depression treatment. The identification of a wide range of predictors for prescribing antidepressants highlights the complexity of depression treatment and the need for individualized approaches that consider patients' comorbidities and previous treatments.The significant impact of comorbidities on the response to treatment makes it improbable that the mechanism of action of antidepressants is solely based on the serotonin hypothesis. It is hard to explain how comorbidities lead to the depletion of serotonin.These findings open up a variety of courses of action for the clinical treatment of depression, each addressing a different source of chronic stress in the brain. Overall, this study contributes to a better understanding of depression treatment and provides valuable insights for clinicians in selecting antidepressants based on patients' medical history.

Effectiveness and Tolerability of Intranasal Esketamine in Treatment-Resistant Depression: Report of Two Clinical Cases

IntroductionMajor depressive disorder (MDD) is a mental health disorder characterised by persistently low mood; anhedonia; feelings of worthlessness and guilt; altered appetite, weight and sleep and suicidal ideation. About one-third of patients do not respond to available antidepressants (AD). Treatment-resistant depression (TRD) is a clinical term used to define a lack of response to two or more AD in patients with MDD that do not respond to other lines of treatment either. TRD is associated with an increased risk of relapse, hospitalisation and suicide. Esketamine is a non-competitive NMDAR antagonist that acts as an antidepressant by modulating glutamatergic neurotransmission, disturbed in MDD patients. It has recently been approved by the European Commission as a fast-acting nasal spray therapy for depression and suicidal ideation after showing effectiveness in TRD patients (Papakostas et al. JCP 2020; 81 4).ObjectivesThe aim of this study is to determine the effectiveness, safety and tolerability of intranasal esketamine in two TRD-diagnosed patients and to assess their clinical evolution.MethodsA prospective study was conducted describing the evolution of two TRD patients treated with intranasal esketamine. We used The Hamilton Depression Rating Scale (HDRS) to quantify the severity of their symptoms and assess their recovery over time, analyzing the score change from baseline to endpoint as a primary outcome of the study. We also applied the Addensbrooke Cognitive Examination (ACE-III) as a tool to establish their cognitive condition before therapy and its evolution. Changes in dosage during treatment, adverse effects, time required for onset of action, clinical outcomes and other variables were also measured.ResultsIntranasal esketamine was administered twice a week during the first 4-week induction phase and weekly during the following 6-month maintenance phase. Dosage of antidepressant was determined depending on each patient’s age and clinical evolution, being 56 mg the initial dose for case 1 (57 years old) and 28 mg for case 2 (71 years old). This antidepressant was effective in both patients in a fast-acting way, with the onset of action occuring within the first two weeks. During the course of treatment, the HDRS score significantly decreased, associated with improvement and remission of depressive symptoms. Cognitive performance got better in both cases. None of the patients discontinued treatment due to adverse effects or lack of efficacy.ConclusionsOur data suggest that intranasal esketamine therapy is a good alternative in TRD patients, being effective, fast-acting and well-tolerated, with a manageable safety profile. Clinical stability was also observed in the medium-term follow-up after the end of treatment. This presents esketamine as a promising therapeutic and effective strategy in MDD patients who are either treatment-resistant or acutely suicidal.Disclosure of InterestNone Declared

Proportion of patients with severe PPD achieving response and remission of depressive and anxiety symptoms in the SKYLARK Study

Proportion of patients with severe PPD achieving response and remission of depressive and anxiety symptoms in the SKYLARK Study