Unipolar Major Depressive Disorder Research Articles

Seizure Duration and Electroconvulsive Therapy in Major Depressive Disorder

Electroconvulsive therapy (ECT), wherein a generalized epileptic seizure is induced, is a treatment for major depressive disorder (MDD). Currently, it is unclear whether there is an association between seizure length and treatment outcome. To explore the association between seizure duration, potential confounding variables, and ECT treatment outcome. This population-based cohort study obtained data from the Swedish National Quality Register for ECT. Patients treated for unipolar MDD with unilateral electrode placement between January 1, 2012, and December 31, 2019, were included. The electroencephalographic (EEG) seizure duration from the first ECT treatment session for each patient was used for analysis. Data analyses were performed between March 2021 and May 2024. The primary outcome was remission, defined as a cutoff score of less than 10 points on the self-assessment version of the Montgomery-Åsberg Depression Rating Scale within 1 week after ECT. Multivariate logistic regression analysis was performed to calculate odds ratios (ORs) between different seizure duration groups. Furthermore, the associations between concomitant use of pharmacological treatments, seizure duration, and remission rate were explored. Among the 6998 patients included, 4229 (60.4%) were female and the mean (SD) age was 55.2 (18.6) years. Overall, 2749 patients (39.3%) achieved remission after ECT. Patients with EEG seizure duration of 60 to 69 seconds had the highest remission rates compared with patients with seizure duration of less than 20 seconds (OR, 2.17; 95% CI, 1.63-2.88; P < .001). Anticonvulsant medications were associated with shorter seizure duration (eg, lamotrigine: β coefficient [SE], -6.02 [1.08]; P < .001) and lower remission rates (eg, lamotrigine: adjusted OR, 0.67; 95% CI, 0.53-0.84; P < .001). This study found an association between seizure length and remission from MDD. Use of anticonvulsant medication during ECT was associated with shorter seizure duration and lower remission rates after ECT.

Patient and provider perspectives on the phenomenon and effective treatment of treatment-resistant depression: A grounded theory

BackgroundTreatment-Resistant Depression (TRD) is a poorly understood but prevalent clinical phenomenon that lacks a widely accepted definition, explanatory model, or set of practice recommendations. It involves a chronic form of unipolar Major Depressive Disorder (MDD) that fails to respond to at least two first-line clinical treatments. TRD affects as many as 70 % of patients who fail to respond to their first trial of antidepressant medication and 60 % of patients who fail to respond to their first phase of psychotherapy. PurposeThis qualitative study aims to develop a model for understanding the phenomenon of unipolar TRD and the practices involved in its effective treatment. MethodsThis study involved a grounded theory analysis of interviews with four adult-American patients with unipolar TRD and five American providers who routinely treat such patients. ResultsA model of unipolar TRD was developed, explaining common etiological and maintaining factors of unipolar TRD and offering recommendations for guiding effective treatment. LimitationsThis study had a small sample size (N = 9) with limited sociodemographic diversity (all Americans; only two females; one racial/ethnic minority; no sexual minorities), which may limit its generalizability. ConclusionsNevertheless, its emergent theory underscores the importance of TRD patients cultivating positive views of medication and psychotherapy while collaborating with their providers to obtain psychoeducation, build mindfulness/coping skills, enhance social support, and re-engage with pleasurable activities. It recommends that mental health providers focus on processing TRD patients’ subjective experiences, validating patients’ frustrations, and monitoring and calibrating patients’ expectations.

Clinical characteristics and treatment exposure of patients with marked treatment-resistant unipolar major depressive disorder: A RECOVER trial report

BackgroundRECOVER is a randomized sham-controlled trial of vagus nerve stimulation and the largest such trial conducted with a psychiatric neuromodulation intervention. ObjectiveTo describe pre-implantation baseline clinical characteristics and treatment history of patients with unipolar, major depressive disorder (MDD), overall and as a function of exposure to interventional psychiatric treatments (INTs), including electroconvulsive therapy, transcranial magnetic stimulation, and esketamine. MethodsMedical, psychiatric, and treatment records were reviewed by study investigators and an independent Study Eligibility Committee prior to study qualification. Clinical characteristics and treatment history (using Antidepressant Treatment History [Short] Form) were compared in those qualified (N = 493) versus not qualified (N = 228) for RECOVER, and among the qualified group as a function of exposure to INTs during the current major depressive episode (MDE). ResultsUnipolar MDD patients who qualified for RECOVER had marked TRD (median of 11.0 lifetime failed antidepressant treatments), severe disability (median WHODAS score of 50.0), and high rate of baseline suicidality (77% suicidal ideation, 40% previous suicide attempts). Overall, 71% had received at least one INT. Compared to the no INT group, INT recipients were younger and more severely depressed (QIDS-C, QIDS-SR), had greater suicidal ideation, earlier diagnosis of MDD, and failed more antidepressant medication trials. ConclusionsRECOVER-qualified unipolar patients had marked TRD and marked treatment resistance with most failing one or more prior INTs. Treatment with ≥1 INTs in the current MDE was associated with earlier age of MDD onset, more severe clinical presentation, and greater treatment resistance relative to patients without a history of INT. Trial registrationClinicalTrials.gov Identifier NCT03887715.

Geographical distance predicts psychiatric treatment retention for Hispanic women with comorbid major depression and breast cancer.

Depression is among the most common comorbid psychiatric disorders of patients with breast cancer. Depression decreases patient quality of life and, if untreated, can adversely affect cancer treatment. We sought to identify treatment barriers for women with breast cancer receiving psychotherapy for depression. Findings may help policy makers and researchers determine funding and design of future studies involving this population, especially in communities with high rates of health disparities. We used data from a randomized trial for women with breast cancer and current DSM-IV non-psychotic unipolar major depressive disorder (MDD). Patients were randomly assigned to 12weeks of one of three psychotherapies and attrition was assessed by whether subjects completed 12 weekly treatment sessions. We used descriptive analyses and logistic regression to identify treatment barriers. R shiny was used to determine study patient residences. Of 134 randomized patients, 84 (62.7%) were Hispanic. Fifty-nine patients (44%) either did not start or dropped out of treatment, 49 (83.1%) of them being Hispanic. Being a Hispanic woman, less educated, and geographically distant from treatment significantly predicted attrition. Single Hispanic mothers had significantly higher attrition risk than married and/or childless women. Identifying barriers to treatment is important to improve treatment adherence for patients with concurrent diagnoses of breast cancer and MDD, especially for traditionally underserved minorities. Additional support such as affordable tele-medicine, multi-language assistance, financial aid for transportation and child-care, and allocation of more funds to address some identified barriers deserve consideration to improve treatment adherence and outcomes.

Childhood Clinical Features Preceding the Onset of Bipolar Versus Major Depressive Disorders During Adolescence

Objective: To identify childhood psychopathological features that predict the onset of adolescent Bipolar (BD) versus Unipolar Major Depressive Disorder (UD) during adolescence. Method: We analyzed clinical data from 495 juveniles diagnosed with DSM-5 UD (n = 359), and BD (n = 136), using bivariate analysis and multivariate logistic regression model. Results: BD subjects exhibited earlier onset of any psychiatric feature compared to UD. Antecedents associated with later BD were: oppositional defiant > specific phobias > ADHD > obsessive compulsive (OCD). Antecedents selectively associated with later UD were: social anxiety and separation anxiety. Factors significantly and independently associated with later BD diagnosis were: [a] emotional dysregulation at onset of the mood disorder; [b] first depressive episode with mixed features; [c] antecedent ADHD; [d] antecedent OCD, and [e] antecedent oppositional-defiance. Conclusion: Identifying developmental differences in BD and UD symptoms can aid clinicians in early identification and treatment planning for bipolar disorder in youth.

Gut microbiome in atypical depression

BackgroundRecent studies showed that immunometabolic dysregulation is related to unipolar major depressive disorder (MDD) and that it more consistently maps to MDD patients endorsing an atypical symptom profile, characterized by energy-related symptoms including increased appetite, weight gain, and hypersomnia. Despite the documented influence of the microbiome on immune regulation and energy homeostasis, studies have not yet investigated microbiome differences among clinical groups in individuals with MDD. MethodsFifteen MDD patients with atypical features according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5)-5, forty-four MDD patients not fulfilling the DSM-5 criteria for the atypical subtype, and nineteen healthy controls were included in the study. Participants completed detailed clinical assessment and stool samples were collected. Samples were sequenced for the prokaryotic 16S rRNA gene, in the V3-V4 variable regions. Only samples with no antibiotic exposure in the previous 12 months and a minimum of >2000 quality-filtered reads were included in the analyses. ResultsThere were no statistically significant differences in alpha- and beta-diversity between the MDD groups and healthy controls. However, within the atypical MDD group, there was an increase in the Verrucomicrobiota phylum, with Akkermansia as the predominant bacterial genus. LimitationsCross-sectional data, modest sample size, and significantly increased body mass index in the atypical MDD group. ConclusionsThere were no overall differences among the investigated groups. However, differences were found at several taxonomic levels. Studies in larger longitudinal samples with relevant confounders are needed to advance the understanding of the microbial influences on the clinical heterogeneity of depression.

NIRS-aided differential diagnosis among patients with major depressive disorder, bipolar disorder, and schizophrenia

BackgroundTo establish a clinically applicable neuroimaging-guided diagnostic support system that uses near-infrared spectroscopy (NIRS) for differential diagnosis at the individual level among major depressive disorder (MDD), bipolar disorder (BPD), and schizophrenia (SZ). MethodsA total of 192 participants were recruited, including 40 patients with MDD, 38 patients with BPD, 65 patients with SZ, and 49 healthy individuals. We analyzed the spatiotemporal characteristics of hemodynamic responses in the frontotemporal cortex during a verbal fluency test (VFT) measured by NIRS to assess the accuracy of single-subject classification for differential diagnosis among the three psychiatric disorders. The optimal threshold of the frontal centroid value (54 seconds) was utilized on the basis of the findings of the Japanese study. ResultsThe application of the optimal threshold of the frontal centroid value (54 seconds) allowed for the accurate differentiation of patients with unipolar MDD (72.5%) from BPD (78.9%) or SZ (84.6%). ConclusionThese results suggest that the NIRS-aided differential diagnosis of major psychiatric disorders can be a promising biomarker in Taiwan. Future multi-site studies are needed to validate our findings.

Determinants and Outcomes of Suicidal Behavior Among Patients With Major Depressive Disorder

Major depressive disorder (MDD) is an important risk factor of suicidal behavior, but the added burden of suicidal behavior and MDD on the patient and societal level, including all-cause mortality, is not well studied. Also, the contribution of various prognostic factors for suicidal behavior has not been quantified in larger samples. To describe the clinical and societal outcomes, including all-cause mortality, of suicidal behavior in patients with MDD and to explore associated risk factors and clinical management to inform future research and guidelines. This population-based cohort study used health care data from the Stockholm MDD Cohort. Patients aged 18 years or older with episodes of MDD diagnosed between January 1, 2012, and December 31, 2017, in any health care setting were included. The dates of the data analysis were February 1 to November 1, 2022. Patients with MDD with and without records of suicidal behavior. The main outcome was all-cause mortality. Secondary outcomes were comorbid conditions, medications, health care resource utilization (HCRU), and work loss. Using Region Stockholm registry variables, a risk score for factors associated with suicidal behavior within 1 year after the start of an MDD episode was calculated. A total of 158 169 unipolar MDD episodes were identified in 145 577 patients; 2240 (1.4%) of these episodes, in 2219 patients, included records of suicidal behavior (mean [SD] patient age, 40.9 [18.6] years; 1415 episodes [63.2%] in women and 825 [36.8%] in men). A total of 11 109 MDD episodes in 9574 matched patients with MDD without records of suicidal behavior were included as controls (mean [SD] patient age, 40.8 [18.5] years; 7046 episodes [63.4%] in women and 4063 [36.6%] in men). The all-cause mortality rate was 2.5 per 100 person-years at risk for the MDD-SB group and 1.0 per 100 person-years at risk for the MDD-non-SB group, based on 466 deaths. Suicidal behavior was associated with higher all-cause mortality (hazard ratio, 2.62 [95% CI, 2.15-3.20]), as well as with HCRU and work loss, compared with the matched controls. Patients with MDD and suicidal behavior were younger and more prone to have psychiatric comorbid conditions, such as personality disorders, substance use, and anxiety, at the start of their episode. The most important factors associated with suicidal behavior within 1 year after the start of an MDD episode were history of suicidal behavior and age, history of substance use and sleep disorders, and care setting in which MDD was diagnosed. This cohort study's findings suggest that high mortality, morbidity, HCRU, and work loss associated with MDD may be substantially accentuated in patients with MDD and suicidal behavior. Use of medication aimed at decreasing the risk of all-cause mortality during MDD episodes should be systematically evaluated to improve long-term outcomes.

Antidepressant continuation and adherence in pregnancy, and risk of antenatal hospitalization for unipolar major depressive and/or anxiety disorders

BackgroundKnowledge about the effectiveness of antidepressants in pregnancy is limited. We aimed to evaluate the association of antidepressant continuation in pregnancy and adherence with the risk of antenatal hospitalization for depression/anxiety. MethodsIn a population-based study based on the healthcare databases of the Lombardy region, Italy (2010–2020), we included 17,033 live-birth pregnancies within 16,091 women with antidepressant use before pregnancy. Antidepressant exposure was classified as continued in pregnancy versus discontinued proximal to pregnancy. Outcome measure was antenatal hospitalization for depression/anxiety. Propensity score matching analysis was performed to control for measured confounding. Stratification by pre-pregnancy antidepressant adherence based on the proportion of days covered (PDC) with antidepressants served to address confounding by disease severity. We applied 60 days lag-time for antidepressant exposure to minimize the risk of protopathic bias. ResultsThere were 362 (2.1 %) antenatal hospitalizations for depression/anxiety. Among the matched pairs, the cumulative incidence was 3.5 (continued antidepressant) versus 2.1 (discontinued antidepressant) per 1000 person-months, yielding a hazard ratio (HR) of 1.76 (95 % confidence interval (CI): 1.34–2.33)). The HR declined to the null (1.02, 95 % CI: 0.62–1.69) in the stratified analysis of pregnancies with moderate-high adherence pre-pregnancy. Moderate-high adherence in pregnancy was associated with 85 % greater risk of the antenatal outcome, but the HR decreased with the 60 days lag-time (HR: 1.40, 95 % CI: 0.79–2.50). LimitationsLack of information regarding antidepressant dosage. ConclusionWe found no difference in risk for antenatal hospitalization for depression/anxiety with antidepressant continuation or higher adherence in pregnancy, relative to discontinuation or lower adherence.

Effectiveness of Genotype-Specific Tricyclic Antidepressant Dosing in Patients With Major Depressive Disorder

Evidence of the clinical benefit of pharmacogenetics-informed treatment (PIT) with antidepressants is still limited. Especially for tricyclic antidepressants (TCAs), pharmacogenetics may be of interest because therapeutic plasma concentrations are well defined, identification of optimal dosing can be time consuming, and treatment is frequently accompanied by adverse effects. To determine whether PIT results in faster attainment of therapeutic TCA plasma concentrations compared with usual treatment in patients with unipolar major depressive disorder (MDD). This randomized clinical trial compared PIT with usual treatment among 111 patients at 4 centers in the Netherlands. Patients were treated with the TCAs nortriptyline, clomipramine, or imipramine, with clinical follow-up of 7 weeks. Patients were enrolled from June 1, 2018, to January 1, 2022. At inclusion, patients had unipolar nonpsychotic MDD (with a score of ≥19 on the 17-item Hamilton Rating Scale for Depression [HAMD-17]), were aged 18 to 65 years, and were eligible for TCA treatment. Main exclusion criteria were a bipolar or psychotic disorder, substance use disorder, pregnancy, interacting comedications, and concurrent use of psychotropic medications. In the PIT group, the initial TCA dosage was based on CYP2D6 and CYP2C19 genotypes. The control group received usual treatment, which comprised the standard initial TCA dosage. The primary outcome was days until attainment of a therapeutic TCA plasma concentration. Secondary outcomes were severity of depressive symptoms (measured by HAMD-17 scores) and frequency and severity of adverse effects (measured by Frequency, Intensity, and Burden of Side Effects Rating scores). Of 125 patients randomized, 111 (mean [SD] age, 41.7 [13.3] years; 69 [62.2%] female) were included in the analysis; of those, 56 were in the PIT group and 55 were in the control group. The PIT group reached therapeutic concentrations faster than the control group (mean [SD], 17.3 [11.2] vs 22.0 [10.2] days; Kaplan-Meier χ21 = 4.30; P = .04). No significant difference in reduction of depressive symptoms was observed. Linear mixed-model analyses showed that the interaction between group and time differed for the frequency (F6,125 = 4.03; P = .001), severity (F6,114 = 3.10; P = .008), and burden (F6,112 = 2.56; P = .02) of adverse effects, suggesting that adverse effects decreased relatively more for those receiving PIT. In this randomized clinical trial, PIT resulted in faster attainment of therapeutic TCA concentrations, with potentially fewer and less severe adverse effects. No effect on depressive symptoms was observed. These findings indicate that pharmacogenetics-informed dosing of TCAs can be safely applied and may be useful in personalizing treatment for patients with MDD. ClinicalTrials.gov Identifier: NCT03548675.

Polyunsaturated fatty acids changes during electroconvulsive therapy in major depressive disorder

Polyunsaturated fatty acids (PUFAs) have important electrochemical properties and have been implicated in the pathophysiology of major depressive disorder (MDD) and its treatment. However, the relation of PUFAs with electroconvulsive therapy (ECT) has never been investigated. Therefore, we aimed to explore the associations between PUFA concentrations and response to ECT in patients with MDD. We included 45 patients with unipolar MDD in a multicentre study. To determine PUFA concentrations, we collected blood samples at the first (T0) and twelfth (T12) ECT-session. We assessed depression severity using the Hamilton Rating Scale for Depression (HAM-D) at T0, T12 and at the end of the ECT-course. ECT-response was defined as ‘early response’ (at T12), ‘late response’ (after ECT-course) and ‘no’ response (after the ECT-course). The PUFA chain length index (CLI), unsaturation index (UI) and peroxidation index (PI) and three individual PUFAs (eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA] and nervonic acid [NA]) were associated with response to ECT using linear mixed models. Results showed a significant higher CLI in ‘late responders’ compared to ‘non responders’. For NA, ‘late responders’ showed significantly higher concentrations compared to ‘early’- and ‘non responders’. In conclusion, this study provides the first indication that PUFAs are associated with the efficacy of ECT. This indicates that PUFAs' influence on neuronal electrochemical properties and neurogenesis may affect ECT outcomes. Thereby, PUFAs form a potentially modifiable factor predicting ECT outcomes, that warrants further investigation in other ECT-cohorts.

Accuracy of the Arabic HCL - 32 and MDQ in detecting patients with bipolar disorder

BackgroundStudies about the two most used and validated instruments for the early detection of Bipolar Disorder (BD), the 32 - item Hypomania Checklist (HCL - 32) and the Mood Disorder Questionnaire (MDQ), are scarce in non-Western countries. This study aimed to explore the reliability, factor structure, and criterion validity of their Arabic versions in a sample of Tunisian patients diagnosed with mood disorders.MethodsThe sample included 59 patients with BD, 86 with unipolar Major Depressive Disorder (MDD) and 281 controls. Confirmatory factor analysis was applied to show that a single global score was an appropriate summary measure of the screeners in the sample. Receiver Operating Characteristic analysis was used to assess the capacity of the translated screeners to distinguish patients with BD from those with MDD and controls.ResultsReliability was good for both tools in all samples. The bifactor implementation of the most reported two-factor model had the best fit for both screeners. Both were able to distinguish patients diagnosed with BD from putatively healthy controls, and equally able to distinguish patients diagnosed with BD from patients with MDD.ConclusionBoth screeners work best in excluding the presence of BD in patients with MDD, which is an advantage in deciding whether or not to prescribe an antidepressant.

Association of Treatment-Resistant Depression With Patient Outcomes and Health Care Resource Utilization in a Population-Wide Study

The totality of the societal and individual impact of treatment-resistant depression (TRD) is unknown, as is the potential to prognosticate TRD. The generalizability of many observational studies on TRD is limited. To estimate the burden of TRD in a large population-wide cohort in an area with universal health care by including data from both health care types (psychiatric and nonpsychiatric) and, further, to develop a prognostic model for clinical use. This cohort study, a population-based observational study, assessed data from the Stockholm MDD Cohort for episodes of major depressive disorder (MDD) between 2010 and 2017 that fulfilled predefined criteria for TRD (≥3 consecutive antidepressant treatments). Data analysis was performed from August 2020 to May 2022. Outcomes were psychiatric and nonpsychiatric comorbid conditions, antidepressant treatments, health care resource utilization, lost workdays, all-cause mortality, and intentional self-harm and, in the prognostic model, TRD. A total of 158 169 unipolar MDD episodes (in 145 577 patients) were identified between January 1, 2012, and December 31, 2017 (64.7% women; median [IQR] age, 42 years [30-56]). Of these, 12 793 episodes (11%) fulfilled criteria for TRD. The median (IQR) time from the start of MDD episode to TRD was 552 days (294-932). Selective serotonin reuptake inhibitor was the most common class of antidepressant treatment in all treatment steps, and 5907 patients (46.2%) received psychotherapy at some point before initiation of the third pharmacological antidepressant treatment. Compared with matched non-TRD episodes, TRD episodes had more inpatient bed-days (mean, 3.9 days; 95% CI, 3.6-4.1, vs 1.3 days; 95% CI, 1.2-1.4) and more lost workdays (mean, 132.3 days; 95% CI, 129.5-135.1, vs 58.7 days; 95% CI, 56.8-60.6) 12 months after the index date. Anxiety, stress, sleep disorder, and substance use disorder were all more common comorbid conditions in TRD episodes. Intentional self-harm was more than 4 times more common in TRD episodes. The all-cause mortality rate for patients with MDD with TRD episodes was 10.7/1000 person-years at risk, compared with 8.7/1000 person-years at risk for patients with MDD without TRD episodes (hazard ratio, 1.23; 95% CI, 1.07-1.41). Median time from start of the first antidepressant treatment to start of the second, and from start of the second antidepressant treatment to start of the third, was 165 and 197 days, respectively. The severity of MDD, defined using the self-rating Montgomery-Åsberg Depression Rating Scale (MADRS-S) at time of MDD diagnosis, was found to be the most important prognostic factor for TRD (C index = 0.69). In this cohort study, TRD was a common variant of MDD when including patients from both health care types, which is associated with a high disease burden for both patients and society. The median time between initiation of new antidepressant treatments was longer than recommended in current treatment guidelines, suggesting room for more structured and timely depression care.

Dissecting the depressed mood criterion in adult depression: The heterogeneity of mood disturbances in major depressive episodes

BackgroundMood disturbances have historically remained a core criterion in diagnosing major depressive episode. DSMs have illustrated this criterion with depressed, hopeless, discouraged, cheerless, and irritable mood, suggesting interchangeability. Extant research has examined individual forms of mood disturbance to depression severity. Less examined is the heterogeneity in mood disturbances and its implication to their association to depression presentations and outcomes. MethodThe current study used a nationally representative sample of U.S. adults with unipolar major depressive disorder to study the association between specific forms of mood disturbances to depression severity, chronicity, or symptoms, above and beyond other forms, as well as their relations to functional impairment, suicidal outcomes, and psychiatric comorbidity via generalized linear models. ResultsCheerless and hopeless mood were associated with depression severity. Hopeless and irritable mood were associated with depression chronicity. Different forms of mood disturbance showed differential relations to depressive symptoms. Cheerless, hopeless, and irritable mood were associated with depression-specific functional interference, incremental to depression severity. Cheerless, hopeless, and discouraged mood were associated with passive suicidal ideation. Hopeless mood was associated with active suicidal ideation. Hopeless and irritable mood were associated with both suicide plan and suicide attempt. Different forms of mood disturbance demonstrated differential associations to comorbid psychiatric conditions. DiscussionThe relations between different forms of mood disturbances and various aspects of depression are nuanced. Theoretically, these relations highlight the potential utility in acknowledging the complexity and heterogeneity in mood disturbances. Clinically, our results suggest potential utility in routinely monitoring mood disturbances.

Commentary on Cochrane review: "Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder".

Cochrane recently published a review of esketamine and other glutamate receptor modulators in depression. To address the limitations of the review, analyses of esketamine data were conducted to provide additional perspective to the reviewers' interpretation of their findings. Response rate, remission rate, and change from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score were determined using data from all esketamine phase 2/3 registration studies of treatment-resistant depression (TRD) and, separately, all esketamine phase 2/3 registration studies of major depressive disorder (MDD) and active suicidal ideation with intent. Outcomes were assessed at all timepoints (i.e., 24 h, 72 h (MDD with active suicidal intent only), and 1, 2, and 4 weeks). Enrollment criteria of the TRD studies were different than those of the studies of MDD and active suicidal ideation with intent, resulting in differences in patients' clinical characteristics and depression severity between the cohorts. Thus, we did not compare results between these cohorts (as was done in the Cochrane review). In the combined TRD studies, a statistically significant between-group difference favored esketamine plus antidepressant over antidepressant plus placebo at 24 h (based on response, remission, and change in MADRS score), 1 week (change in MADRS score), 2 weeks (response and change in MADRS score), and 4 weeks (response, remission, and change in MADRS score). In the combined studies of MDD and active suicidal ideation with intent, the between-group difference was statistically different, favoring esketamine plus standard-of-care over placebo plus standard-of-care, at 24 h (response, remission, and change in MADRS score), 72 h and 1 week (change in MADRS score), 2 weeks (response), and 4 weeks (response, remission, and change in MADRS score). For both study types, the between-group difference in outcomes was not statistically significant at the other timepoints. Esketamine improves response, remission, and depressive symptoms as early as 24 h post-first dose among patients with TRD and among patients with MDD and active suicidal ideation with intent.

Individual Prediction of Remission Based on Clinical Features Following Electroconvulsive Therapy

Objective: Previous prediction models for electroconvulsive therapy (ECT) responses have predominantly been based on neuroimaging data, which has precluded widespread application for severe cases in real-world clinical settings. The aims of this study were (1) to build a clinically useful prediction model for ECT remission based solely on clinical information and (2) to identify influential features in the prediction model.Methods: We conducted a retrospective chart review to collect data (registered between April 2012 and March 2019) from individuals with depression (unipolar major depressive disorder or bipolar disorder) diagnosed via DSM-IV-TR criteria who received ECT at Keio University Hospital. Clinical characteristics were used as candidate features. A light gradient boosting machine was used for prediction, and 5-fold cross-validation was performed to validate our prediction model.Results: In total, 177 patients with depression underwent ECT during the study period. The remission rate was 63%. Our model predicted individual patient outcomes with 71% accuracy (sensitivity, 86%; specificity, 46%). A shorter duration of the current episodes, lower baseline severity, higher dose of antidepressant medications before ECT, and lower body mass index were identified as important features for predicting remission following ECT.Conclusions: We developed a prediction model for ECT remission based solely on clinical information. Our prediction model demonstrated accuracy comparable to that in previous reports. Our model suggests that introducing ECT earlier in the treatment course may contribute to improvements in clinical outcomes.

Is there a 'bipolar iceberg' in UK primary care psychological therapy services?

Improving Access to Psychological Therapies (IAPT) is a primary care therapy service commissioned by England's National Health Service (NHS) for people with unipolar depression and anxiety-related disorders. Its scope does not extend to 'severe mental illness', including bipolar disorders (BD), but evidence suggests there is a high BD prevalence in ostensibly unipolar major depressive disorder (uMDD) samples. This study aimed to indicate the prevalence and characteristics of people with BD in a naturalistic cohort of IAPT patients. 371 participants were assessed before initiating therapy. Participants were categorised by indicated diagnoses: BD type-I (BD-I) or type-II (BD-II) as defined using a DSM diagnostic interview, bipolar spectrum (BSp, not meeting diagnostic criteria but exceeding BD screening thresholds), lifetime uMDD or other. Information about psychiatric history and co-morbidities was examined, along with symptoms before and after therapy. 368 patients provided sufficient data to enable classification. 10% of participants were grouped as having BD-I, 20% BD-II, 40% BSp, 25% uMDD and 5% other. BD and uMDD participants had similar demographic characteristics, but patients meeting criteria for BD-I/BD-II had more complex psychiatric presentations. All three 'bipolar' groups had particularly high rates of anxiety disorders. IAPT therapy receipt was comparable between groups, as was therapy response (F9704 = 1.113, p = 0.351). Notwithstanding the possibility that bipolar diathesis was overestimated, findings illustrate a high prevalence of BD in groups of people notionally with uMDD or anxiety. As well as improving the detection of BD, further substantive investigation is required to establish whether individuals affected by BD should be eligible for primary care psychological intervention.

Mixed features in depression: frequency and associated factors

Introduction Mixed states in mood disorders present significant clinical and prognostic challenges. Although the DSM-5 has broadened diagnostic criteria for mixed states with the development of the ‘mixed features’ specifier and its application to unipolar depressive disorders, some mixed episodes might still be overlooked.Objectivesto evaluate the frequency and the factors associated with mixed depression according to the broader Koukopoulos criteria in a sample of patients with a major depressive episodeMethodsWe included 99 consecutive patients presenting for a major depressive episode of bipolar (n=10) or unipolar major depressive (n=89) disorder at our outpatient clinic. Major depression was ascertained using SCID- IV criteria, and mixed features were determined using Koukopoulos’ diagnostic criteriaResults Mean age of the sample was 35.5 years [14-58]. Women accounted for 63.6% of patients. Mixed features were found in 19.5% (n=19) of the sample, 80% (n=8) among patients with bipolar disorders (BD) and 12.3% (n=11) among those with major depressive disorder (MDD). Individuals with mixed features had more substance abuse (p=0.005) and more suicide attempts (p=0.01). Individuals receiving antipsychotics had a lower risk of mixed features (p=0.000) while antidepressant treatment did not have any affect. A family history of BD, psychosis, suicide and substance abuse were found in these patients. Mixed features in depression were more frequent in patients with BD than in MDD.ConclusionsOur study showed a high frequency of mixed features in depression, especially bipolar depression when Koukopoulos criteria are applied. Special attention should be given to these patients given the association with substance use and suicidalityDisclosureNo significant relationships.

Catatonia; A Case Study and Literature Review

IntroductionCatatonia is a state of apparent unresponsiveness to external stimuli in a person who is awake. More common in patients with unipolar major depression or bipolar disorder. Common signs: immobility, rigidity, mutism, posturing, excessive motor activity, stupor, negativism, staring, and echolalia. We will discuss a case of a 23 year old male with schizophrenia presented with catatonia and decompensation of his schizophrenia in the context of medication non-compliance. We will discuss findings from litrature pertaining to catatonia and treatment strategies.Objectives- To discuss catatonia, its incidence in different psychiatric disorders. - To discuss literature pertaining to catatonia. - To discuss different treatment strategiesMethods- Case studyResults- Signs of catatonia: immobility, mutism, withdrawal and refusal to eat, staring, negativism, posturing, rigidity, waxy flexibility/catalepsy, stereotypy, echolalia, or echopraxia, verbigeration. - Diagnosis: Clinical, Lorazepam challenge. Bush-Francis Catatonia Rating Scale (BFCRS) - BFCR scale is used as the screening tool. If 2 of the 14 are positive, prompts further evaluation and completion of the remaining 9 items. - Differential Diagnosis include; Neuroleptic Malignant Syndrome, Serotoninergic Syndrome, Malignant Hyperthermia, Akinetic Mutism, Delirium, Parkinson’s disease. - Lorazepam can be scheduled at interval doses until the catatonia resolves. - ECT in combination with benzodiazepines is used to treat malignant catatonia. - Possible complications are Physical trauma, malignant catatonia (autonomic instability, life-threatening), dehydration, pneumonia, pressure ulcers due to immobility, muscle contractions, DVT, PEConclusionsPsychiatrists need to be diligent in evaluating patients with Catatonia for other comorbid psychiatric conditions, addressing these conditions and conducting a thorough assessment and prompt treatment.DisclosureNo significant relationships.

For adults with unipolar major depressive disorder, how does ketamine compare with midazolam?

For adults with unipolar major depressive disorder, how does ketamine compare with midazolam?