Duration of Adjunctive Antidepressant Maintenance in Bipolar I Depression.

BACKGROUND: Antidepressants are used to treat acute depression in patients with bipolar I disorder, but their effect as maintenance treatment after the remission of depression has not been well studied. METHODS: We conducted a multisite, double-blind, randomized, placebo-controlled trial of maintenance of treatment with adjunctive escitalopram or bupropion XL as compared with discontinuation of antidepressant therapy in patients with bipolar I disorder who had recently had remission of a depressive episode. Patients were randomly assigned in a 1:1 ratio to continue treatment with antidepressants for 52 weeks after remission or to switch to placebo at 8 weeks. The primary outcome, assessed in a time-to-event analysis, was any mood episode, as defined by scores on scales measuring symptoms of hypomania or mania, depression, suicidality, and mood-episode severity; additional treatment or hospitalization for mood symptoms; or attempted or completed suicide. Key secondary outcomes included the time to an episode of mania or hypomania or depression. RESULTS: Of 209 patients with bipolar I disorder who participated in an open-label treatment phase, 150 who had remission of depression were enrolled in the double-blind phase in addition to 27 patients who were enrolled directly. A total of 90 patients were assigned to continue treatment with the prescribed antidepressant for 52 weeks (52-week group) and 87 were assigned to switch to placebo at 8 weeks (8-week group). The trial was stopped before full recruitment was reached owing to slow recruitment and funding limitations. At 52 weeks, 28 of the patients in the 52-week group (31%) and 40 in the 8-week group (46%) had a primary-outcome event. The hazard ratio for time to any mood episode in the 52-week group relative to the 8-week group was 0.68 (95% confidence interval [CI], 0.43 to 1.10; P = 0.12 by log-rank test). A total of 11 patients in the 52-week group (12%) as compared with 5 patients in the 8-week group (6%) had mania or hypomania (hazard ratio, 2.28; 95% CI, 0.86 to 6.08), and 15 patients (17%) as compared with 35 patients (40%) had recurrence of depression (hazard ratio, 0.43; 95% CI, 0.25 to 0.75). The incidence of adverse events was similar in the two groups. CONCLUSIONS: In a trial involving patients with bipolar I disorder and a recently remitted depressive episode, adjunctive treatment with escitalopram or bupropion XL that continued for 52 weeks did not show a significant benefit as compared with treatment for 8 weeks in preventing relapse of any mood episode. The trial was stopped early owing to slow recruitment and funding limitations. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00958633.).

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 Update on Clinical Guidelines for Management of Major Depressive Disorder in Adults: Réseau canadien pour les traitements de l'humeur et de l'anxiété (CANMAT) 2023 : Mise à jour des lignes directrices cliniques pour la prise en charge du trouble dépressif majeur chez les adultes.

BACKGROUND: The Canadian Network for Mood and Anxiety Treatments (CANMAT) last published clinical guidelines for the management of major depressive disorder (MDD) in 2016. Owing to advances in the field, an update was needed to incorporate new evidence and provide new and revised recommendations for the assessment and management of MDD in adults. METHODS: CANMAT convened a guidelines editorial group comprised of academic clinicians and patient partners. A systematic literature review was conducted, focusing on systematic reviews and meta-analyses published since the 2016 guidelines. Recommendations were organized by lines of treatment, which were informed by CANMAT-defined levels of evidence and supplemented by clinical support (consisting of expert consensus on safety, tolerability, and feasibility). Drafts were revised based on review by patient partners, expert peer review, and a defined expert consensus process. RESULTS: The updated guidelines comprise eight primary topics, in a question-and-answer format, that map a patient care journey from assessment to selection of evidence-based treatments, prevention of recurrence, and strategies for inadequate response. The guidelines adopt a personalized care approach that emphasizes shared decision-making that reflects the values, preferences, and treatment history of the patient with MDD. Tables provide new and updated recommendations for psychological, pharmacological, lifestyle, complementary and alternative medicine, digital health, and neuromodulation treatments. Caveats and limitations of the evidence are highlighted. CONCLUSIONS: The CANMAT 2023 updated guidelines provide evidence-informed recommendations for the management of MDD, in a clinician-friendly format. These updated guidelines emphasize a collaborative, personalized, and systematic management approach that will help optimize outcomes for adults with MDD.

The Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Recommendations for the Use of Racemic Ketamine in Adults with Major Depressive Disorder: Recommandations Du Groupe De Travail Du Réseau Canadien Pour Les Traitements De L'humeur Et De L'anxiété (Canmat) Concernant L'utilisation De La Kétamine Racémique Chez Les Adultes Souffrant De Trouble Dépressif Majeur.

OBJECTIVE: Patients with major depressive disorder often have limited response to first-line and second-line medications; hence, novel pharmacological treatments are needed for treatment-resistant depression (TRD). Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, has demonstrated rapid antidepressant effects in patients with TRD. The Canadian Network for Mood and Anxiety Treatments (CANMAT) convened a task force to review the evidence for efficacy and safety of racemic ketamine and to provide recommendations for its use in clinical practice. METHODS: A systematic review was conducted with computerized search of electronic databases up to January 31, 2020 using combinations of search terms, inspection of bibliographies, and review of other ketamine guidelines and consensus statements. The level of evidence and lines of treatment were assigned according to CANMAT criteria. Recommendations were given in question-answer format. RESULTS: Intravenous (IV) racemic ketamine given as a single infusion has Level 1 evidence for efficacy in adults with TRD. The evidence for multiple infusions, given as an acute series or as ongoing maintenance treatment, is limited to Level 3. Adverse events associated with ketamine infusions include behavioral (e.g., dissociative symptoms) and physiological (e.g., hypertension) events. There is only Level 3 or 4 evidence for non-IV formulations of racemic ketamine. Consensus recommendations are given for clinical administration of IV ketamine including patient selection, facility and personnel issues, monitoring, and maintaining response. CONCLUSIONS: Single-dose IV racemic ketamine is a third-line recommendation for adults with TRD. The need for repeated and maintenance ketamine infusions should be carefully assessed on a case-by-case basis with consideration of potential risks and benefits. Because of limited evidence for efficacy and risk for misuse and diversion, the use of oral and other formulations of racemic ketamine should be limited to specialists with ketamine-prescribing expertise and affiliations with tertiary or specialized centers.

Evaluating the use of electroconvulsive therapy in low-middle income countries: A narrative review.

BACKGROUND: Electroconvulsive therapy (ECT) is a well-accepted intervention for treatment-resistant, serious mental illnesses. Its acceptability, efficacy, and tolerability are well documented in high-income settings, but less so in lower- and middle-income countries (LMICs). This report is a narrative review of ECT practice in the latter setting. METHODS: A literature search was conducted using Medline and PubMed. Initial results yielded 81 publications in English. Following the screening, 19 papers were included to evaluate the information on ECT practice and perceptions. RESULTS: Reports from LMICs on efficacy, tolerability, and perceptions of ECT were relatively sparse. In general, they confirm its use mostly for treatment-resistant major mental illnesses (i.e., depression, schizophrenia, bipolar disorder). Both modified and unmodified forms of ECT are used and considered equally effective, although the former is better tolerated. Use of unmodified ECT remains significant in LMICs due to its low cost and limited resource requirements. In general, there is satisfaction with ECT and its outcomes. The education of patients and families, content process, and research have been noted as areas to improve. CONCLUSIONS: ECT is perceived as an effective intervention in LMICs, but use of unmodified ECT remains controversial. There is a need for the development and use of global guidelines to improve clinician training, knowledge sharing with patients and their families, and outcome research.

Proteoglycans in breast cancer, identification and characterization by LC-MS/MS assisted proteomics approach: A review.

PURPOSE: Proteoglycans (PGs) are negatively charged macromolecules containing a core protein and single or several glycosaminoglycan chains attached by covalent bond. They are distributed in all tissues, including extracellular matrix (ECM), cell surface, and basement membrane. They are involved in major pathways and cell signalling cascades which modulate several vital physiological functions of the body. They have also emerged as a target molecule for cancer treatment and as possible biomarkers for early cancer detection. Among cancers, breast cancer is a highly invasive and heterogenous type and has become the major cause of mortality especially among women. So, this review revisits the studies on PGs characterization in breast cancer using LC-MS/MS-based proteomics approach, which will be further helpful for identification of potential PGs-based biomarkers or therapeutic targets. EXPERIMENTAL DESIGN: There is a lack of comprehensive knowledge on the use of LC-MS/MS-based proteomics approaches to identify and characterize PGs in breast cancer. RESULTS: LC-MS/MS assisted PGs characterization in breast cancer revealed the vital PGs in breast cancer invasion and progression. In addition, comprehensive profiling and characterization of PGs in breast cancer are efficiently carried out by this approach. CONCLUSIONS: Proteomics techniques including LC-MS/MS-based identification of proteoglycans is effectively carried out in breast cancer research. Identification of expression at different stages of breast cancer is a major challenge, and LC-MS/MS-based profiling of PGs can boost novel strategies to treat breast cancer, which involve targeting PGs, and also aid early diagnosis using PGs as biomarkers.

Randomized, Placebo-Controlled Effectiveness Study of Quetiapine XR in Comorbid Depressive and Anxiety Disorders.

Objective: Quetiapine is approved as an adjunctive treatment for major depressive disorder (MDD) and as monotherapy for bipolar depression. It is often used off-label for treating anxiety conditions and as an augmentation agent for treatment-resistant depression. However, its benefit in depression with comorbid anxiety disorders has not been systematically evaluated. The current study evaluated the benefit and tolerability of quetiapine as augmentation to first-line antidepressants for MDD comorbid with anxiety disorders.Methods: In this multicenter trial (June 2008-June 2013), 76 adults (aged 18-65 years) with a primary diagnosis of unipolar depression comorbid with at least 1 anxiety disorder (per DSM-IV-TR criteria) received flexible-dose quetiapine extended-release (XR) 50-300 mg/d or placebo as add-on for 12 weeks in a 2:1 ratio. Depression, anxiety, life satisfaction, and adverse events were assessed.Results: Depression, anxiety, and function improved significantly in both groups. On primary outcome measures, quetiapine was superior to placebo in improving depression (17-item Hamilton Depression Rating Scale score: mean difference = -3.64; 95% CI, -7.01 to -0.27) and anxiety symptoms (Hamilton Anxiety Rating Scale score: mean difference = -4.02; 95% CI, -7.41 to -0.64), as well as Clinical Global Impressions-Severity of Illness scale score (mean difference = -0.64; 95% CI, -1.13 to -0.15). On secondary measures including the Montgomery-Asberg Depression Rating Scale, Beck Depression Inventory, Penn State Worry Questionnaire, and Quality of Life Satisfaction and Enjoyment Questionnaire, quetiapine produced a greater degree of improvement compared to placebo, but group differences were not statistically significant. Quetiapine was well tolerated, with mostly minor and no serious adverse effects.Conclusions: Quetiapine augmentation may be a useful intervention for MDD with comorbid anxiety.Trial Registration: ClinicalTrials.gov Identifier: NCT00688818.

Treatments for child and adolescent attention deficit hyperactivity disorder in low and middle-income countries: A narrative review.

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder that affects approximately 2-7 % of children globally and is associated with a myriad of difficulties that have long-term consequences. Most children and adolescents live in low- and middle-income countries (LMICs), but there are few reports and no consolidation of findings on ADHD treatment outcomes in this population. We conducted a review of ADHD treatment literature for children and adolescents living in LMICs. METHODS: Studies were identified using databases (PsychoINFO, Pubmed, MEDLINER, EMBASE, Global Health, Academic Search Complete, Google Scholar). The initial search produced 139 articles. These were filtered for language, title, abstract, and full-text keyword identification to yield a final 20 articles to be included in this review. RESULTS: Reports on outcomes of both psychological and pharmacological treatment were relatively sparse, particularly the former, which mostly referred to parent training and multimodal programs in pre-school children. Most evidence exists for the benefit of methylphenidate-IR with a few reports on other agents, including clonidine, atomoxetine, and lisdexamfetamine. Methylphenidate is the most common agent to treat ADHD in youth in LMICs. Younger age, combined subtype, and comorbid oppositional defiant disorder were associated with poorer treatment outcome. CONCLUSION: Access to treatment for ADHD is overall limited in LMICs and varied among individual countries. Pharmacological treatments were generally more available than psychological interventions. Several barriers including stigma, cost, and lack of resources were reported to impact treatment acceptance. More research in LMICs is needed to improve and expand mental health services in these regions.

Characteristics of psychomotor retardation distinguishes patients with depression using multichannel near-infrared spectroscopy and finger tapping task.

BACKGROUND: Psychomotor retardation (PMR) is frequently noted as a characteristic feature of major depressive disorder (MDD). In patients with depression, it is characterized by retardation of speech, emotion, thinking, and cognition. This study explored the activation pattern of the prefrontal cortex (PFC) during the finger-tapping task (FTT) in subjects with MDD, aiming to provide additional understanding on the connection between PMR and PFC activation pattern in depression through the use of near-Infrared Spectroscopy (NIRS). We hypothesized that, through use of NIRS during the FTT, motor retardation in depression would generate a distinct PFC activation pattern, allowing for differentiation between patients with MDD and healthy controls (HCs). METHODS: Thirty-five patients with MDD and thirty-nine HCs underwent NIRS evaluation during performance of the FTT. The FTT included both left-finger tapping and right-finger tapping performed by a computer screen. Each participant was assessed using a 45-channel NIRS and various clinical scales. FINDINGS: During the left-FTT, the left orbitofrontal cortex (OFC) showed higher oxy-hemoglobin (Oxy-Hb) activation in the MDD group when compared to the HCs. During the right-FTT, the right dorsolateral prefrontal cortex (DLPFC) demonstrated lower Oxy-Hb activation, and the dorsomedial prefrontal cortex (DMPFC) showed higher Oxy-Hb activation in the MDD group versus the HC group. CONCLUSION: Our results demonstrated different activation patterns of the PFC between the MDD and HC groups, using FTT as a motor performance task. In particular, the OFC, the DLPFC and the DMPFC areas hold promise as new useful sites for such differentiation in future investigations.

Association of intranasal esketamine, a novel 'standard of care' treatment and outcomes in the management of patients with treatment-resistant depression: protocol of a prospective cohort observational study of naturalistic clinical practice.

INTRODUCTION: Esketamine is the S-enantiomer of racemic ketamine and has been approved by the Food and Drug Administration for the management of treatment resistant depression, demonstrating effective and long-lasting benefits. The objective of this observational study is to elucidate the association of intranasal (IN) esketamine with beneficial and negative outcomes in the management of treatment resistant major depressive disorder. METHODS AND ANALYSIS: This is a multicentre prospective cohort observational study of naturalistic clinical practice. We expect to recruit 10 patients per research centre (6 centres, total 60 subjects). After approval to receive IN esketamine as part of their standard of care management of moderate to severe treatment resistant depression, patients will be invited to participate in this study. Association of esketamine treatment with outcomes in the management of depression will be assessed by measuring the severity of depression symptoms using the Montgomery-Åsberg Depression Rating Scale (MADRS), and tolerability by systematically tracking common side effects of ketamine treatment, dissociation using the simplified 6-Item Clinician Administered Dissociative Symptom Scale and potential for abuse using the Likeability and Craving Questionnaire (LCQ). Change in depressive symptoms (MADRS total scores) over time will be evaluated by within-subject repeated measures analysis of variance. We will calculate the relative risk associated with the beneficial (reduction in total scores for depression) outcomes, and the side effect and dropout rates (tolerability) of adding IN esketamine to patients' current pharmacological treatments. Covariate analysis will assess the impact of site and demographic variables on treatment outcomes. ETHICS AND DISSEMINATION: Approval to perform this study was obtained through the Health Sciences Research Ethics Board at Queen's University. Findings will be shared among collaborators, through departmental meetings, presented on different academic venues and publishing our manuscript.

Prevalence and correlates of suicidal ideation among the general population in China during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is a major threat to the public. However, the comprehensive profile of suicidal ideation among the general population has not been systematically investigated in a large sample in the age of COVID-19. METHODS: A national online cross-sectional survey was conducted between February 28, 2020 and March 11, 2020 in a representative sample of Chinese adults aged 18 years and older. Suicidal ideation was assessed using item 9 of the Patient Health Questionnaire-9. The prevalence of suicidal ideation and its risk factors was evaluated. RESULTS: A total of 56,679 participants (27,149 males and 29,530 females) were included. The overall prevalence of suicidal ideation was 16.4%, including 10.9% seldom, 4.1% often, and 1.4% always suicidal ideation. The prevalence of suicidal ideation was higher in males (19.1%) and individuals aged 18-24 years (24.7%) than in females (14.0%) and those aged 45 years and older (11.9%). Suicidal ideation was more prevalent in individuals with suspected or confirmed infection (63.0%), frontline workers (19.2%), and people with pre-existing mental disorders (41.6%). Experience of quarantine, unemployed, and increased psychological stress during the pandemic were associated with an increased risk of suicidal ideation and its severity. However, paying more attention to and gaining a better understanding of COVID-19-related knowledge, especially information about psychological interventions, could reduce the risk. CONCLUSIONS: The estimated prevalence of suicidal ideation among the general population in China during COVID-19 was significant. The findings will be important for improving suicide prevention strategies during COVID-19.

Differentiating between bipolar and unipolar depression using prefrontal activation patterns: Promising results from functional near infrared spectroscopy (fNIRS) findings.

BACKGROUND: Bipolar depression (BD) is a unique, severe and prevalent mental illness that shares many similarities in symptoms with unipolar depression (UD). Improving precision of their diagnoses would enhance treatment outcome and prognosis for both conditions. This study aims to provide evidence from functional Near-Infrared Spectroscopy (fNIRS) as a potential tool to differentiate UD and BD based on their differences in hemodynamic change in the prefrontal cortex during verbal fluency tasks (VFT). METHODS: We enrolled 179 participants with clinically confirmed diagnoses, including 69 UD patients, 68 BD patients and 42 healthy controls(HC). Every participant was assessed using a 45-channel fNIRS and various clinical scales. FINDINGS: Compared with HC, region-specific fNIR leads show UD patients had significant lower hemodynamic activation in 4 particular pre-frontal regions: 1) the left dorsolateral prefrontal cortex (DLPFC), 2) orbitofrontal cortex (OFC), 3) bilateral ventrolateral prefrontal cortex (VLPFC) and 4) left inferior frontal gyrus (IFG). In contrast, BD vs. HC comparisons showed only significant lower hemodynamic activation in the LIFG area. Furthermore, compared to BD patients, UD patients showed decreased hemodynamic activation changes in the VLPFC region. CONCLUSION: Our results show significant frontal lobe activation pattern differences between UD and BD groups. fNIRS can be a potential tool to increase diagnostic precision for these conditions. In particular, the VLPFC area holds promise to be a useful site for such differentiation for further investigations.