Culturally Adapted Cognitive Behaviour Therapy (CaCBT) to Improve Community Mental Health Services for Canadians of South Asian Origin: A Qualitative Study.

BACKGROUND: South Asian (SA) Canadians are disproportionately affected by higher rates of mood and anxiety disorders. SA Canadians with depression report significant barriers to accessing mental health care and the highest proportion of unmet mental health needs. The Mental Health Commission of Canada (MHCC) advocates for culturally and linguistically relevant services for SA Canadians. Culturally adapted cognitive behavior therapy (CaCBT) has shown to be more effective than standard cognitive behavior therapy (CBT). Adapting CBT for the growing SA population in Canada will ensure equitable access to effective, culturally-appropriate mental health interventions. METHOD: The study used a qualitative design to elicit stakeholder consultation via in-depth interviews. This study is reported using the criteria included in Consolidated Criteria for Reporting Qualitative Studies (COREQ). The analysis follows an ethnographic approach and was informed by the principles of emergent design. RESULTS: Five themes were identified from the analysis, (i) Awareness and preparation: factors that impact the individual's understanding of therapy and mental illness. (ii) Access and provision: SA Canadians' perception of barriers, facilitators, and access to treatment. (iii) Assessment and engagement: experiences of receiving helpful treatment. (iv) Adjustments to therapy: modifications and suggestions to standard CBT. (v) Ideology and ambiguity: racism, immigration, discrimination, and other socio-political factors. CONCLUSIONS: Mainstream mental health services need to be culturally appropriate to better serve SA Canadians experiencing depression and anxiety. Services must understand the family dynamics, cultural values and socio-political factors that impact SA Canadians to reduce attrition rates in therapy.

Psychosocial and pharmacological interventions for personality disorders in low- and middle-income countries: A systematic review.

Personality disorders (PDs) have a global prevalence of 7.8% and are associated with increased rates of morbidity and mortality. Most research on PDs has been conducted in High Income Countries (HICs). We conducted a systematic review to investigate the effectiveness of psychosocial and pharmacological interventions for personality disorders (PDs) in individuals from Low- and Middle-Income Countries (LMICs.) We systematically searched MEDLINE, Embase, APA PsycInfo, Web of Science, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and The Cochrane Library from inception to January 5, 2023. Inclusion criteria were quantitative studies and grey literature where participants received a psychosocial or pharmacological intervention for PD. Exclusion criteria were qualitative studies, review articles, studies in which PD was not the primary condition, and articles not available in English. The Cochrane Risk of Bias tool version 2.0 and Joanna Briggs Institute instruments were used to measure risk of bias. Studies were pooled by type of study, PD investigated, type of intervention, assessment methods, and outcomes. Sixteen studies met inclusion criteria and were included. Fifteen were intervention studies related to borderline PD. Only one studied mixed PDs. Twelve studies were of psychotherapy, one pharmacotherapy, one combination of both, and two neurostimulation. Most of the studies showed improvement in symptoms though data was largely collected using self-report measures. There were only six RCTs. There is a dearth of literature on interventions for PDs in LMICs and funding bodies should prioritize research in LMICs. Systematic Review Registration Number: PROSPERO CRD42021233415.

Prevalence of suicidal ideation and suicide attempts in individuals with psychosis and bipolar disorder in South Asia: systematic review and meta-analysis.

BACKGROUND: Suicidal ideation and attempts are growing public health concerns globally. Evidence from high-income countries suggests that individuals with psychosis and bipolar disorder are at increased risk of suicidal ideation and attempts, but there is a scarcity of evidence from South Asia. AIMS: To estimate the prevalence of suicidal ideation and attempts in individuals with psychosis and bipolar disorder in South Asia. METHOD: In this systematic review and meta-analysis, four databases (PsycINFO, Web of Science, EMBASE and Medline) were searched until December 2022. Pooled prevalence was estimated with random-effects models. Heterogeneity was quantified with the I2-statistic. RESULTS: The pooled sample size across the 21 studies was 3745 participants, 1941 (51.8%) of which were male. The pooled prevalence of suicide attempts in South Asian people with either psychosis or bipolar disorder was 22% (95% CI 17-27; n = 15). The pooled prevalence of suicidal ideation with psychosis or bipolar disorder combined was 38% (95% CI 27-51; n = 10). Meta-regression, subgroup and sensitivity analysis showed that the pooled prevalence estimates for both suicide attempt and ideation remained unaffected by variations in critical appraisal ratings and study designs. Only one study reported data on suicide-related deaths. CONCLUSIONS: One in four individuals diagnosed with psychosis or bipolar disorder have reported suicide attempts, whereas up to one in three have experienced suicidal ideation. These findings underscore the urgent need for clinicians to regularly assess and monitor suicidal ideation and attempts among individuals with these disorders in South Asia.

Protocol for a systematic review and meta-analysis of coordinate-based network mapping of brain structure in bipolar disorder across the lifespan.

BACKGROUND: Studies about brain structure in bipolar disorder have reported conflicting findings. These findings may be explained by the high degree of heterogeneity within bipolar disorder, especially if structural differences are mapped to single brain regions rather than networks. AIMS: We aim to complete a systematic review and meta-analysis to identify brain networks underlying structural abnormalities observed on T1-weighted magnetic resonance imaging scans in bipolar disorder across the lifespan. We also aim to explore how these brain networks are affected by sociodemographic and clinical heterogeneity in bipolar disorder. METHOD: We will include case-control studies that focus on whole-brain analyses of structural differences between participants of any age with a standardised diagnosis of bipolar disorder and controls. The electronic databases Medline, PsycINFO and Web of Science will be searched. We will complete an activation likelihood estimation analysis and a novel coordinate-based network mapping approach to identify specific brain regions and brain circuits affected in bipolar disorder or relevant subgroups. Meta-regressions will examine the effect of sociodemographic and clinical variables on identified brain circuits. CONCLUSIONS: Findings from this systematic review and meta-analysis will enhance understanding of the pathophysiology of bipolar disorder. The results will identify brain circuitry implicated in bipolar disorder, and how they may relate to relevant sociodemographic and clinical variables across the lifespan.

Psilocybin for treatment-resistant depression without psychedelic effects: study protocol for a 4-week, double-blind, proof-of-concept randomised controlled trial.

BACKGROUND: Randomised controlled trials (RCTs) of psilocybin have reported large antidepressant effects in adults with major depressive disorder and treatment-resistant depression (TRD). Given psilocybin's psychedelic effects, all published studies have included psychological support. These effects depend on serotonin 2A (5-HT2A) receptor activation, which can be blocked by 5-HT2A receptor antagonists like ketanserin or risperidone. In an animal model of depression, ketanserin followed by psilocybin had similar symptomatic effects as psilocybin alone. AIMS: To conduct a proof-of-concept RCT to (a) establish feasibility and tolerability of combining psilocybin and risperidone in adults with TRD, (b) show that this combination blocks the psychedelic effects of psilocybin and (c) provide pilot data on the antidepressant effect of this combination (compared with psilocybin alone). METHOD: In a 4-week, three-arm, 'double dummy' trial, 60 adults with TRD will be randomised to psilocybin 25 mg plus risperidone 1 mg, psilocybin 25 mg plus placebo, or placebo plus risperidone 1 mg. All participants will receive 12 h of manualised psychotherapy. Measures of feasibility will include recruitment and retention rates; tolerability and safety will be assessed by rates of drop-out attributed to adverse events and rates of serious adverse events. The 5-Dimensional Altered States of Consciousness Rating Scale will be a secondary outcome measure. RESULTS: This trial will advance the understanding of psilocybin's mechanism of antidepressant action. CONCLUSIONS: This line of research could increase acceptability and access to psilocybin as a novel treatment for TRD without the need for a psychedelic experience and continuous monitoring.

Suicide and Self-Harm Among Immigrant Youth to Ontario, Canada From Muslim Majority Countries: A Population-Based Study.

OBJECTIVE: To examine the association between Muslim religious affiliation and suicide and self-harm presentations among first- and second-generation immigrant youth. METHODS: We performed a population-based cohort study involving individuals aged 12 to 24 years, living in Ontario, who immigrated to Canada between 1 January 2003 and 31 May 2017 (first generation) and those born to immigrant mothers (second generation). Health administrative and demographic data were used to analyze suicide and self-harm presentations. Sex-stratified logistic regression models generated odds ratios (OR) for suicide and negative binomial regression models generated rate ratios (aRR) for self-harm presentations, adjusting for refugee status and time since migration. RESULTS: Of 1,070,248 immigrant youth (50.1% female), there were 129,919 (23.8%) females and 129,446 (24.2%) males from Muslim-majority countries. Males from Muslim-majority countries had lower suicide rates (3.8/100,000 person years [PY]) compared to males from Muslim-minority countries (5.9/100,000 PY) (OR: 0.62, 95% CI, 0.42-0.92). Rates of suicide between female Muslim-majority and Muslim-minority groups were not different (Muslim-majority 1.8/100,000 PY; Muslim-minority 2.2/100,000 PY) (OR: 0.82, 95% CI, 0.46-1.47). Males from Muslim-majority countries had lower rates of self-harm presentations than males from Muslim-minority (<10%) countries (Muslim majority: 12.2/10,000 PY, Muslim-minority: 14.1/10,000 PY) (aRR: 0.82, 95% CI, 0.75, 0.90). Among female immigrants, rates of self-harm presentations were not different among Muslim-majority (30.1/10,000 PY) compared to Muslim-minority (<10%) (32.9/10,000 PY) (aRR: 0.93, 95% CI, 0.87-1.00) countries. For females, older age at immigration conferred a lower risk of self-harm presentations. CONCLUSION: Being a male from a Muslim-majority country may confer protection from suicide and self-harm presentations but the same was not observed for females. Approaches to understanding the observed sex-based differences are warranted.

Systematic review of structured care pathways in major depressive disorder and bipolar disorder.

BACKGROUND: Structured care pathways (SCPs) consist of treatment algorithms that patients advance through with the goal of achieving remission or response. These SCPs facilitate the application of current evidence and adequate treatment, which potentially benefit patients with mood disorders. The aim of this systematic review was to provide an updated synthesis of SCPs for the treatment of depressive disorders and bipolar disorder (BD). METHOD: PubMed, PsycINFO, and Embase were searched through June 2022 for peer-reviewed studies examining outcomes of SCPs. Eligibility criteria included being published in a peer-reviewed journal in the English language, reporting of intervention used in the SCP, and having quantitative outcomes. Studies Cochrane risk of bias tool was used to assess quality of RCTs. RESULTS: Thirty-six studies including 15,032 patients were identified for qualitative synthesis. Six studies included patients with BD. The studies were highly heterogeneous in design, outcome measures, and algorithms. More than half of the studies reported superiority of SCPs over treatment as usual, suggesting that the standardized structure and consistent monitoring inherent in SCPs may be contributing to their effectiveness. We also found accumulating evidence supporting feasibility of SCPs in different settings, although dropout rates were generally higher in SCPs. The studies included were limited to being published in peer-reviewed journals in English language. The heterogeneity of studies did not allow quantitative evaluation. CONCLUSIONS: The findings of our study suggest that SCPs are equally or more effective than treatment as usual in depression and BD. Further studies are required to ascertain their effectiveness, particularly for BD, and to identify factors that influence their feasibility and success.

Single-dose psilocybin for a treatment-resistant episode of major depression: Impact on patient-reported depression severity, anxiety, function, and quality of life.

BACKGROUND: COMP360 is a proprietary, synthetic formulation of psilocybin being developed for treatment-resistant depression (TRD), a burdensome, life-threatening illness with high global impact. Here, we expand upon the previous report of primary outcomes from a phase 2 study of COMP360 in individuals with TRD-the largest randomised controlled clinical trial of psilocybin-to discuss findings of the exploratory efficacy endpoints. METHODS: In this phase 2, double-blind trial, 233 participants with TRD were randomised to receive a single dose of psilocybin 25 mg, 10 mg, or 1 mg (control), administered alongside psychological support from trained therapists. Efficacy measures assessed patient-reported depression severity, anxiety, positive and negative affect, functioning and associated disability, quality of life, and cognitive function. RESULTS: At Week 3, psilocybin 25 mg, compared with 1 mg, was associated with greater improvements from Baseline total scores in all measures. The 10 mg dose produced smaller effects across these measures. LIMITATIONS: Interpretation of this trial is limited by the absence of an active comparator and the possibility of functional unblinding in participants who received a low dose of psilocybin. CONCLUSIONS: Three weeks after dosing, psilocybin 25 mg and, to a lesser degree, 10 mg improved measures of patient-reported depression severity, anxiety, affect, and functioning. These results extend the primary findings from the largest randomised clinical trial of psilocybin for TRD to examine other outcomes that are of importance to patients.

Brief App-Based Cognitive Behavioral Therapy for Anxiety Symptoms in Psychiatric Inpatients: Feasibility Randomized Controlled Trial.

BACKGROUND: Psychiatric inpatients often have limited access to psychotherapeutic education or skills for managing anxiety, a common transdiagnostic concern in severe and acute mental illness. COVID-19-related restrictions further limited access to therapy groups on inpatient psychiatric units. App-based interventions may improve access, but evidence supporting the feasibility of their use, acceptability, and effectiveness in psychiatric inpatient settings is limited. MindShift CBT is a free app based on cognitive behavioral therapy principles with evidence for alleviating anxiety symptoms in the outpatient setting. OBJECTIVE: We aimed to recruit 24 participants from an acute general psychiatric inpatient ward to a 1-month randomized control study assessing the feasibility and acceptability of providing patients with severe and acute mental illness access to the MindShift CBT app for help with managing anxiety symptoms. METHODS: Recruitment, data collection, analysis, and interpretation were completed collaboratively by clinician and peer researchers. Inpatients were randomized to two conditions: treatment as usual (TAU) versus TAU plus use of the MindShift CBT app over 6 days. We collected demographic and quantitative data on acceptability and usability of the intervention. Symptoms of depression, anxiety, and psychological distress were measured in pre- and poststudy surveys for preliminary signals of efficacy. We conducted individual semistructured interviews with participants in the MindShift CBT app group at the end of their trial period, which were interpreted using a standardized protocol for thematic analysis. RESULTS: Over 4 weeks, 33 inpatients were referred to the study, 24 consented to participate, 20 were randomized, and 11 completed the study. Of the 9 randomized participants who did not complete the study, 7 were withdrawn because they were discharged or transferred prior to study completion, with a similar distribution among both conditions. Among the enrolled patients, 65% (13/20) were admitted for a psychotic disorder and no patient was admitted primarily for an anxiety disorder. The average length of stay was 20 days (SD 4.4; range 3-21) and 35% (7/20) of patients were involuntarily admitted to hospital. Small sample sizes limited accurate interpretation of the efficacy data. Themes emerging from qualitative interviews included acceptability and usability of the app, and patient agency associated with voluntary participation in research while admitted to hospital. CONCLUSIONS: Our study benefitted from collaboration between peer and clinician researchers. Due to rapid patient turnover in the acute inpatient setting, additional flexibility in recruitment and enrollment is needed to determine the efficacy of using app-based psychotherapy on an acute psychiatric ward. Despite the limited sample size, our study suggests that similar interventions may be feasible and acceptable for acutely unwell inpatients. Further study is needed to compare the efficacy of psychotherapeutic apps with existing standards of care in this setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT04841603; https://clinicaltrials.gov/ct2/show/NCT04841603.

Astrocytes in the Neuropathology of Bipolar Disorder: Review of Current Evidence.

(1) Background: Approximately one-third of patients with bipolar disorder (BD) do not experience sustained remission with current treatments. Presently, astrocytes, i.e., glial cells that act as key regulators of neuroinflammation, have been a target for therapeutic development. Research regarding their role in the neuropathology of BD is limited. We conducted a scoping review on evidence linking astrocytes to the pathology of BD. (2) Methods: The search was conducted in MEDLINE for studies published from inception to August 2022. Studies of interest were data-extracted and reported based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocols. (3) Results: Overall, 650 publications were identified, of which 122 full texts were evaluated and 12 included. Four were in vitro, seven were ex vivo, and one study was both in vitro and in vivo. In vitro investigations focused on plasma levels of neuroinflammatory biomarkers S100B and glial fibrillary acidic protein (GFAP). Ex vivo investigations were post-mortem brain studies assessing astrocytes in regions of interest (i.e., anterior cingulate cortex, dorsolateral prefrontal cortex) using phosphorylated GFAP and ASCT-1. The in vivo and in vitro study evaluated morphological and chemical variations of YKL-40 between cohorts. (4) Conclusions: Reports indicate an association between astrocyte dysfunction and BD although larger studies are required to validate this association.

A century of research on psychedelics: A scientometric analysis on trends and knowledge maps of hallucinogens, entactogens, entheogens and dissociative drugs.

A scientometric analysis was realized to outline clinical research on psychedelics over the last century. Web of Science Core Collection was searched up to March 18, 2022, for publications on psychedelics. Network analyses and bibliometrics were combined, to identify research themes and trends with Bibliometrix and CiteSpace. The primary aim was to measure research trends evolution over time, and the secondary aims were to identify bibliometric performance and influence networks of publications, authors, institutions, and countries. Sensitivity analyses were conducted for 2016-2022, and 2021 time periods. We included 31,687 documents (591,329 references), which aggregated into a well-structured network with credible clustering. Research productivity was split into an early less productive period mainly focusing on safety issues, and a "psychedelic renaissance" after the 1990s. Major trends were identified for hallucinogens/entheogens, entactogens, novel psychoactive substances (NPS), and on dissociative substances. There was a translational evolution from the bench to the bedside, with phase 2 and 3 trials and/or evidence synthesis in particular. The most recent trends concerned NPS, ketamine-associated brain changes, and ayahuasca-assisted psychotherapy. The USA and Canada were the most productive settings for the research overall, and more recently this geographical distribution became more prominent, reflecting legislative context/policy making. A translational evolution of psychedelics has been occurring, that has brought approval of esketamine for depression and will likely lead to approval of additional psychedelics across mental and physical conditions. Toxicology screening tools for NPS are urgently needed, which in turn might follow the same translational evolution of psychedelics in the future.

Serotonergic psychedelics for depression: What do we know about neurobiological mechanisms of action?

Introduction: Current treatment options for major depressive disorder (MDD) have limited efficacy and are associated with adverse effects. Recent studies investigating the antidepressant effect of serotonergic psychedelics-also known as classic psychedelics-have promising preliminary results with large effect sizes. In this context, we conducted a review of the putative neurobiological underpinnings of the mechanism of antidepressant action of these drugs. Methods: A narrative review was conducted using PubMed to identify published articles evaluating the antidepressant mechanism of action of serotonergic psychedelics. Results: Serotonergic psychedelics have serotonin (5HT)2A agonist or partial agonist effects. Their rapid antidepressant effects may be mediated-in part-by their potent 5HT2A agonism, leading to rapid receptor downregulation. In addition, these psychedelics impact brain derived neurotrophic factor and immunomodulatory responses, both of which may play a role in their antidepressant effect. Several neuroimaging and neurophysiology studies evaluating mechanistic change from a network perspective can help us to further understand their mechanism of action. Some, but not all, data suggest that psychedelics may exert their effects, in part, by disrupting the activity of the default mode network, which is involved in both introspection and self-referential thinking and is over-active in MDD. Conclusion: The mechanisms of action underlying the antidepressant effect of serotonergic psychedelics remains an active area of research. Several competing theories are being evaluated and more research is needed to determine which ones are supported by the most robust evidence.

Targeting Metabolic Dysfunction for the Treatment of Mood Disorders: Review of the Evidence.

Major depressive disorder (MDD) and bipolar disorder (BD) are often chronic with many patients not responding to available treatments. As these mood disorders are frequently associated with metabolic dysfunction, there has been increased interest in novel treatments that would target metabolic pathways. The objectives of this scoping review were to synthesize evidence on the impact on mood symptoms of lipid lowering agents and anti-diabetics drugs, while also reviewing current knowledge on the association between mood disorders and dyslipidemia or hyperglycemia. We propose that metabolic dysfunction is prevalent in both MDD and BD and it may contribute to the development of these disorders through a variety of pathophysiological processes including inflammation, brain structural changes, hormonal alterations, neurotransmitter disruptions, alteration on brain cholesterol, central insulin resistance, and changes in gut microbiota. Current evidence is conflicting on the use of statins, polyunsaturated fatty acids, thiazolidinediones, glucagon-like peptide agonists, metformin, or insulin for the treatment of MDD and BD. Given the paucity of high-quality randomized controlled trials, additional studies are needed before any of these medications can be repurposed in routine clinical practice. Future trials need to enrich patient recruitment, include evaluations of mechanism of action, and explore differential effects on specific symptom domains such as anhedonia, suicidality, and cognition.

Relationship between childhood trauma, personality, social support and depression in women attending general medical clinics in a low and middle-income country.

BACKGROUND: Associations between childhood trauma, personality, and Major Depressive Disorder (MDD) have been well established in studies conducted in high-income countries. However, there are limited studies on these associations in low and middle-income countries (LMICs), where MDD is highly prevalent. We assessed the relationships between childhood trauma, personality, and MDD in women in Karachi, Pakistan. METHOD: In this cross-sectional study of 455 female patients attending general medical outpatient clinics, a diagnosis of MDD was confirmed using the Structured Clinical Interview for DSM-IV (SCID); retrospective reports of childhood trauma were collected using the childhood trauma questionnaire (CTQ); and Big Five personality traits were assessed using the NEO Personality Inventory Revised (NEO PI-R). Other measures included the Life Events Questionnaire (LEQ) and the Multidimensional Scale of Perceived Social Support (MSPSS). Factors independently associated with MDD were determined using logistic regression analyses. RESULTS: Of the 455 women recruited between August 1, 2011 and July 31, 2013, 242 (53%) had a diagnosis of MDD. Women with MDD were significantly more likely to be separated, had more stressful life events and higher CTQ scores. Higher perceived social support, conscientiousness and extraversion were independently associated with significantly reduced odds of MDD. There were no significant associations between CTQ scores and any of the NEO PI-R subscales. LIMITATIONS: Ratings of childhood trauma were based on retrospective recall. CONCLUSION: MDD and a history of childhood trauma were highly prevalent in Pakistani women attending general medical clinics. Interventions to prevent childhood trauma and promote social support in women may improve public mental health in LMICs like Pakistan.

An integrated parenting intervention for maternal depression and child development in a low-resource setting: Cluster randomized controlled trial.

BACKGROUND: Rates of depression among Pakistani mothers are high, leading to poor developmental outcomes in their children. This study tested the effectiveness of a manualized integrated parenting program; Learning through Play Plus (LTP+) for maternal depression in Karachi, Pakistan. METHODS: A cluster randomized control trial conducted from January 2014 to December 2015 across 120 villages in Karachi. A total of 774 depressed mothers aged 18-44 years with children aged 0-30 months old, were included. Villages were randomized to receive LTP+ added to treatment as usual (TAU) or TAU alone. Primary outcomes were severity of maternal depression at 3 and 6 months measured by the Edinburgh Postnatal Depression Scale and child socio-emotional development at 6 months measured by the Ages and Stages Questionnaire (ASQ). Secondary outcomes included maternal anxiety, quality of life, social support, parenting competence, and knowledge about child development. RESULTS: Mothers in the LTP+ group reported significantly lower depression scores compared to those in the TAU group (6.6 vs. 13.8, effect size [ES]: -7.2; 95% confidence interval [CI]: -8.2, -6.1) at 3 and 6 months (7.2 vs. 12.00; ES: -4.6; 95% CI: -5.9, -3.4). Child socio-emotional development at 6 months was significantly better in the LTP+ group on all domains of the ASQ. There were also statistically significant improvements on all secondary outcomes at 3- and 6-month follow-up. CONCLUSION: In low-resource settings like Pakistan, low-cost integrated parenting interventions delivered by lay health workers can provide effective treatment for depressed mothers, leading to improvements in child development.

Suicidality in patients with bipolar depression: Findings from a lower middle-income country.

The prevalence and risk factors of suicidal ideation in bipolar depression in low- and middle-income countries (LMICs) are poorly understood. This study is a secondary, cross-sectional analysis of a randomized controlled trial from Pakistan, a lower middle-income country. Participants included psychiatric outpatients aged 18 to 65 with a known diagnosis of bipolar disorder and currently in a depressive episode. Suicidality was assessed using the suicide item of the 17-item Hamilton Depression Rating Scale (HAM-D) and levels of severity were categorized as absent, mild/moderate, or severe. Biometric data and biomarkers were obtained. Descriptive statistics were used to describe prevalence and logistic regression applied to establish correlates to suicidal ideation. Among the 266 participants, 67% indicated suicidality of any level and 16% endorsed severe suicidality. Lower body mass index (BMI) (OR = 0.93, 95% CI = 0.88-0.98), higher HAM-D score (OR = 1.29, 95% CI = 1.16-1.43), lower C-reactive protein (CRP) level (OR = 0.53, 95% CI = 0.40-0.70), and increased number of inpatient hospitalizations (OR = 1.16, 95% CI = 1.03-1.31) were identified as significant predictors of suicidality in the fully adjusted regression model. Our findings add to the limited literature on suicidality in bipolar disorder in the LMIC context and suggest roles of biological variables such as BMI and CRP level in predicting suicidal ideation and potentially suicidal behaviours in bipolar depression.

The prevalence, odds and predictors of lifespan comorbid eating disorder among people with a primary diagnosis of bipolar disorders, and vice-versa: Systematic review and meta-analysis.

BACKGROUND: There are scarce and discrepant data about the prevalence and correlates of co-occurring eating disorders (EDs) among people with a primary diagnosis of bipolar disorder (BD), and vice-versa, compelling a systematic review and meta-analysis on the matter. METHODS: MEDLINE/PsycINFO databases were systematically searched for original studies documenting BD⇌ED comorbidity across the lifespan, from inception up until April 20th, 2020. Random-effects meta-analysis and meta-regression analyses were conducted, accounting for multiple moderators. RESULTS: Thirty-six studies involved 15,084 primary BD patients. Eleven studies encompassed 15,146 people with primary EDs. Binge eating disorder (BED) occurred in 12.5% (95%C.I.=9.4-16.6%, I2=93.48%) of BDs, while 9.1% (95%C.I.=3.3-22.6%) of BEDs endorsed BD. Bulimia Nervosa (BN) occurred in 7.4% (95%C.I.=6-10%) of people with BD, whereas 6.7% (95%C.I.=12-29.2%) of subjects with BN had a diagnosis of BD. Anorexia Nervosa (AN) occurred in 3.8% (95%C.I.=2-6%) of people with BDs; 2% (95%C.I.=1-2%) of BD patients had a diagnosis of AN. Overall, BD patients with EDs had higher odds of being female vs. non-ED controls. Several moderators yielded statistically significant differences both within- and between different types of BDs and EDs. LIMITATIONS: Scant longitudinal studies, especially across different EDs and pediatric samples. High heterogeneity despite subgroup comparisons. Limited discrimination of the quality of the evidence. CONCLUSIONS: The rates of BD⇌ED comorbidity vary across different diagnostic groups, more than they do according to the "direction" of BD⇌ED. Further primary studies should focus on the risks, chronology, clinical impact, and management of the onset of intertwined BD⇌ED across different ages, promoting a continuum approach.

Minocycline as adjunctive treatment for major depressive disorder: Pooled data from two randomized controlled trials.

BACKGROUND: Randomized controlled clinical trials that have investigated minocycline as an adjunctive treatment for major depressive disorder have proved promising. Data from two studies were pooled to evaluate more definitively whether the addition of minocycline to standard treatment for major depressive disorder leads to an improvement of depressive symptoms when compared with placebo. METHODS: Both studies were multi-site, double-blinded, placebo-controlled trials of minocycline 200 mg/day added to treatment as usual during a 12-week period. The primary outcome measure was change in depressive symptoms (Montgomery-Asberg Depression Rating Scale in Dean et al. and Hamilton Depression Rating Scale in Husain et al.). Secondary outcomes were change in depression severity (Montgomery-Asberg Depression Rating Scale for Dean et al. and 9-item Patient Health Questionnaire in Husain et al.), anxiety severity (Hamilton Anxiety Rating Scale in Dean et al. and Generalized Anxiety Disorder 7-item scale in Husain et al.) and functional status, which were also evaluated as potential mediators on the primary outcome. RESULTS: A total of 112 participants were included in the pooled data (Dean et al., n = 71; Husain et al., n = 41). A significant change from baseline to week 12 was noted in depressive symptoms - differential change (Placebo vs Minocycline): 9.0, 95% confidence interval = [4.2, 13.9], Cohen's D (95% confidence interval): 0.71 [0.29, 1.14], p < 0.001 - anxiety severity - differential change (Placebo vs Minocycline): 0.38, confidence interval = [0.00, 0.75], Cohen's D (95% confidence interval): 0.41 [0.00, 0.82], p = 0.050) and functional status - differential change (Placebo vs Minocycline): 1.0, 95% confidence interval = [0.4, 1.5], Cohen's D (95% confidence interval): 0.76 [0.34, 1.19], p = 0.001). Duration of illness, current use of benzodiazepine and pain medication were identified as moderators, whereas functional status as a mediator/predictor. CONCLUSION: The improvement of depressive symptoms, anxiety severity and functional status is promising and suggests that minocycline has potential as an adjunctive treatment for major depressive disorder. However, further studies are warranted to confirm therapeutic effects of minocycline in major depressive disorder. TRIAL REGISTRATIONS: NCT02263872, registered October 2014, and ACTRN12612000283875, registered March 2012.

Relative effectiveness of augmentation treatments for treatment-resistant depression: a systematic review and network meta-analysis.

Most interventions for treatment-resistant depression (TRD) are added as augmenters. We aimed to determine the relative effectiveness of augmentation treatments for TRD. This systematic review and network meta-analysis (NMA) sought all randomized trials of pharmacological and psychological augmentation interventions for adults meeting the most common clinical criteria for TRD. The NMA compared the intervention effectiveness of depressive symptoms for TRD augmentation. Of 36 included trials, 27 were suitable for inclusion in NMA, and no psychological trials could be included in the absence of a common comparator. Antipsychotics (13 trials), mood stabilizers (three trials), NMDA-targeting medications (five trials), and other mechanisms (3 trials) were compared against placebo. NMDA treatments were markedly superior to placebo (ES = 0.91, 95% CI 0.67 to 1.16) and head-to-head NMA suggested that NMDA therapies had the highest chance of being an effective treatment option compared to other pharmacological classes. This study provides the most comprehensive evidence of augmenters' effectiveness for TRD, and our GRADE recommendations can be used to guide guidelines to optimize treatment choices. Although conclusions are limited by paucity of, and heterogeneity between, trials as well as inconsistent reports of treatment safety. This work supports the use of NMDA-targeting medications such as ketamine.