Exploring Clinical Subgroups of Participants with Major Depressive Disorder that may Benefit from Adjunctive Minocycline Treatment.

Objective: : To explore illness-related factors in patients with major depressive disorder (MDD) recipients of adjunctive minocycline (200 mg/day) treatment. The analysis included participants experiencing MDD from a 12-week, double blind, placebo-controlled, randomized clinical trial (RCT). Methods: : This is a sub-analysis of a RCT of all 71 participants who took part in the trial. The impact of illness chronicity (illness duration and number of depressive episodes), systemic illness (endocrine, cardiovascular and obesity), adverse effects and minocycline were evaluated as change from baseline to endpoint (12-week) using ANCOVA. Results: : There was a consistent but statistically non-significant trend on all outcomes in favour of the use of adjunctive minocycline for participants without systemic illness, less illness chronicity, and fewer adverse effects. Conclusion: : Understanding the relationship between MDD and illness chronicity, comorbid systemic illness, and adverse effects, can potentially better characterise those individuals who are more likely to respond to adjunctive anti-inflammatory medications.

Comorbidity between major depressive disorder and physical diseases: a comprehensive review of epidemiology, mechanisms and management.

Populations with common physical diseases - such as cardiovascular diseases, cancer and neurodegenerative disorders - experience substantially higher rates of major depressive disorder (MDD) than the general population. On the other hand, people living with MDD have a greater risk for many physical diseases. This high level of comorbidity is associated with worse outcomes, reduced adherence to treatment, increased mortality, and greater health care utilization and costs. Comorbidity can also result in a range of clinical challenges, such as a more complicated therapeutic alliance, issues pertaining to adaptive health behaviors, drug-drug interactions and adverse events induced by medications used for physical and mental disorders. Potential explanations for the high prevalence of the above comorbidity involve shared genetic and biological pathways. These latter include inflammation, the gut microbiome, mitochondrial function and energy metabolism, hypothalamic-pituitary-adrenal axis dysregulation, and brain structure and function. Furthermore, MDD and physical diseases have in common several antecedents related to social factors (e.g., socioeconomic status), lifestyle variables (e.g., physical activity, diet, sleep), and stressful live events (e.g., childhood trauma). Pharmacotherapies and psychotherapies are effective treatments for comorbid MDD, and the introduction of lifestyle interventions as well as collaborative care models and digital technologies provide promising strategies for improving management. This paper aims to provide a detailed overview of the epidemiology of the comorbidity of MDD and specific physical diseases, including prevalence and bidirectional risk; of shared biological pathways potentially implicated in the pathogenesis of MDD and common physical diseases; of socio-environmental factors that serve as both shared risk and protective factors; and of management of MDD and physical diseases, including prevention and treatment. We conclude with future directions and emerging research related to optimal care of people with comorbid MDD and physical diseases.

Distress, burden, and wellbeing in siblings of people with mental illness: a mixed studies systematic review and meta-analysis.

BACKGROUND: Family members of people with mental illness (MI) may experience a host of psychological adversities such as increased stress, burden, and reduced wellbeing. However, relatively little is known about siblings. This study aimed to characterise the experience of distress (viz. depressive and anxiety symptoms), burden, and wellbeing in siblings of people with MI. METHODS: Studies reporting on quantitative measures of depression, anxiety, burden, or wellbeing in siblings; and/or qualitative findings on siblings' experience were eligible. The literature search was conducted up until 20th October 2022. RESULTS: Sixty-two studies comprising data from 3744 siblings were included. The pooled mean percentage of depressive symptoms fell in the mild range at 15.71 (k = 28, N = 2187, 95% CI 12.99-18.43) and anxiety symptoms fell in the minimal range at 22.45 (k = 16, N = 1122, 95% CI 17.09-27.80). Moderator analyses indicate that siblings of people with a schizophrenia spectrum disorder experience greater depressive symptoms than siblings of people with other types of MI (ß = -16.38, p < 0.001). Qualitative findings suggest that individuals may be particularly vulnerable during their siblings' illness onset and times of relapse. Limited communication, confusion about MI, and the need to compensate may contribute to siblings' distress and/or burden. Siblings' experience of wellbeing and caregiving were closely related. CONCLUSION: This review highlights the complex psychological experience of siblings and the need for greater research and clinical support for this important yet often overlooked cohort.

Minocycline as Treatment for Psychiatric and Neurological Conditions: A Systematic Review and Meta-Analysis.

Minocycline has anti-inflammatory, antioxidant, and anti-apoptotic properties that explain the renewed interest in its use as an adjunctive treatment for psychiatric and neurological conditions. Following the completion of several new clinical trials using minocycline, we proposed an up-to-date systematic review and meta-analysis of the data available. The PICO (patient/population, intervention, comparison and outcomes) framework was used to search 5 databases aiming to identify randomized controlled trials that used minocycline as an adjunctive treatment for psychiatric and neurological conditions. Search results, data extraction, and risk of bias were performed by two independent authors for each publication. Quantitative meta-analysis was performed using RevMan software. Literature search and review resulted in 32 studies being included in this review: 10 in schizophrenia, 3 studies in depression, and 7 in stroke, with the benefit of minocycline being used in some of the core symptoms evaluated; 2 in bipolar disorder and 2 in substance use, without demonstrating a benefit for using minocycline; 1 in obsessive-compulsive disorder, 2 in brain and spinal injuries, 2 in amyotrophic lateral sclerosis, 1 in Alzheimer's disease, 1 in multiple systems atrophy, and 1 in pain, with mixes results. For most of the conditions included in this review the data is still limited and difficult to interpret, warranting more well-designed and powered studies. On the other hand, the studies available for schizophrenia seem to suggest an overall benefit favoring the use of minocycline as an adjunctive treatment.

Adjunctive minocycline for major depressive disorder: A sub-study exploring peripheral immune-inflammatory markers and associated treatment response.

Background: Adjunctive minocycline shows promise in treating affective and psychotic disorders; however, the therapeutic mechanism remains unclear. Identifying relevant biomarkers may enhance the efficacy of novel adjunctive treatment candidates. We thus investigated the peripheral immune-inflammatory profile in a randomized controlled trial (RCT) of minocycline in major depressive disorder (MDD). Methods: This sub-study investigated serum samples from a RCT evaluating minocycline (200 mg/day, 12 weeks) in addition to treatment as usual for MDD (ACTRN12612000283875). Of the original sample (N = 71), serum assays were conducted in 47 participants (placebo n = 24; minocycline n = 23) targeting an array of 46 immune-inflammatory analytes including cytokines, chemokines, and acute-phase reactants. General estimating equations (GEE) were used to assess whether analyte concentration at baseline (effect modification) and change in analytes (change association) influenced change in Montgomery-Åsberg Depression Rating Scale (MADRS) score over time. The Benjamini-Hochberg approach was applied when adjusting for false discovery rates (FDR). Results: GEE models revealed several interaction effects. After adjusting for FDR several change association-models survived correction. However, no such models remained significant for effect modification. Three-way group × time × marker interactions were significant for complement C3 (B = -10.46, 95%CI [-16.832, -4.095], q = 0.019) and IL-1Ra (B = -9.008, 95%CI [-15.26, -2.751], q = 0.036). Two-way group × biomarker interactions were significant for ICAM-1/CD54 (B = -0.387, 95%CI [-0.513, -0.26], q < 0.001) and IL-8/CXCL8 (B = -4.586, 95%CI [-7.698, -1.475], q = 0.036) indicating that increases in the serum concentration of these analytes were associated with an improvement in MADRS scores in the minocycline group (compared with placebo). Conclusions: Change in complement C3, IL-1Ra, IL-8/CXCL8, and ICAM-1 may be associated with greater change in depressive scores following adjunctive minocycline treatment in MDD. Further investigations are needed to assess the utility of these biomarkers.

Psychological distress in siblings of people with mental illness: A systematic review and meta-analysis.

OBJECTIVE: The objective of this study was to characterise the prevalence and/or severity of psychological distress (namely, depression and anxiety symptoms) in siblings of people with mental illness (MI) and to examine correlates of distress in siblings of people with MI. METHOD: Studies comparing distress in individuals with and without a sibling with MI were eligible. Studies reporting on correlates of distress in siblings were also eligible. A search of MEDLINE Complete, PsycINFO and Embase was conducted up until 17 March 2022. RESULTS: Fifteen studies comprising 2304 siblings and 2263 comparison individuals were included. Meta-analyses indicated individuals with a sibling with MI experience significantly greater depressive symptoms (Hedges's g = 0.53, 95% CI = [0.32, 0.73], siblings n = 1962, comparison individuals n = 2248) and anxiety symptoms (Hedges's g = 0.40, 95% CI = [0.19, 0.61], siblings n = 653, comparison individuals n = 533) than those without. The sibling relationship, siblings' locus of control, interpersonal functioning and their appraisal of the impacts of MI were identified as important and potentially modifiable correlates. CONCLUSION: Individuals with a sibling with MI experience greater depressive and anxiety symptoms than those without and would likely benefit from support. Future studies are required to elucidate the mechanisms underlying distress in siblings.

Cost-Utility and Cost-effectiveness of MoodSwings 2.0, an Internet-Based Self-management Program for Bipolar Disorder: Economic Evaluation Alongside a Randomized Controlled Trial.

BACKGROUND: Internet-delivered psychosocial interventions can overcome barriers to face-to-face psychosocial care, but limited evidence supports their cost-effectiveness for people with bipolar disorders (BDs). OBJECTIVE: This study aimed to conduct within-trial cost-effectiveness and cost-utility analyses of an internet-based intervention for people with BD, MoodSwings 2.0, from an Australian health sector perspective. METHODS: MoodSwings 2.0 included an economic evaluation alongside an international, parallel, and individually stratified randomized controlled trial comparing an internet-based discussion forum (control; group 1), a discussion forum plus internet-based psychoeducation (group 2), and a discussion forum plus psychoeducation and cognitive behavioral tools (group 3). The trial enrolled adults (aged 21 to 65 years) with a diagnosis of BD assessed by telephone using a structured clinical interview. Health sector costs included intervention delivery and additional health care resources used by participants over the 12-month trial follow-up. Outcomes included depression symptoms measured by the Montgomery-Åsberg Depression Rating Scale (MADRS; the trial primary outcome) and quality-adjusted life years (QALYs) calculated using the short-form 6-dimension instrument derived from the 12-item version of the short-form health survey. Average incremental cost-effectiveness (cost per MADRS score) and cost-utility (cost per QALY) ratios were calculated using estimated mean differences between intervention and control groups from linear mixed effects models in the base case. RESULTS: In total, 304 participants were randomized. Average health sector cost was lowest for group 2 (Aus $9431, SD Aus $8540; Aus $1=US $0.7058) compared with the control group (Aus $15,175, SD Aus $17,206) and group 3 (Aus $15,518, SD Aus $30,523), but none was statistically significantly different. The average QALYs were not significantly different among the groups (group 1: 0.627, SD 0.062; group 2: 0.618, SD 0.094; and group 3: 0.622, SD 0.087). The MADRS scores were previously shown to differ significantly between group 2 and the control group at all follow-up time points (P<.05). Group 2 was dominant (lower costs and greater effects) compared with the control group for average incremental cost per point decrease in MADRS score over 12 months (95% CI dominated to Aus $331). Average cost per point change in MADRS score for group 3 versus the control group was dominant (95% CI dominant to Aus $22,585). Group 2 was dominant (95% CI Aus $43,000 to dominant) over the control group based on lower average health sector cost and average QALY benefit of 0.012 (95% CI -0.009 to 0.033). Group 3, compared with the control group, had an average incremental cost-effectiveness ratio of dominant (95% CI dominated to Aus $19,978). CONCLUSIONS: Web-based psychoeducation through MoodSwings 2.0 has the potential to be a cost-effective intervention for people with BD. Additional research is needed to understand the lack of effectiveness for the addition of cognitive behavioral tools with the group 3 intervention.

Coping with COVID-19: Exploring coping strategies, distress, and post-traumatic growth during the COVID-19 pandemic in Australia.

Objective: This study aimed to explore coping strategies, distress, and post-traumatic growth among Australians with and without a history of a mental health diagnosis during the COVID-19 pandemic. Materials and methods: Australians (N = 381) completed an online survey between 4-August 2020 and 25-October-2020. Coping strategies, distress, and post-traumatic growth were ascertained via the Brief COPE, Depression Anxiety and Stress Scale (DASS-21), and Post-Traumatic Growth Inventory (PTGI), respectively. Linear regression was conducted to examine the relationship between the Brief COPE, DASS-21, and PTGI, adjusting for sociodemographic factors. Models were conducted separately for those with/without a history of a mental health diagnosis. Results: Higher distress was found among those with a history of a mental health diagnosis. Significant differences in the types of coping strategies associated with distress and post-traumatic growth were identified between the groups, however, behavioral disengagement and self-blame consistently predicted depression, anxiety, and stress. For those with a history of a mental health diagnosis, positive reframing decreased anxiety. Self-distraction was associated with post-traumatic growth across both groups. Conclusion: There are important differences in the way people with and without a history of a mental health diagnosis cope with the COVID-19 pandemic.

Exploring interleukin-6, lipopolysaccharide-binding protein and brain-derived neurotrophic factor following 12 weeks of adjunctive minocycline treatment for depression.

This study aimed to explore effects of adjunctive minocycline treatment on inflammatory and neurogenesis markers in major depressive disorder (MDD). Serum samples were collected from a randomised, placebo-controlled 12-week clinical trial of minocycline (200 mg/day, added to treatment as usual) for adults (n = 71) experiencing MDD to determine changes in interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP) and brain derived neurotrophic factor (BDNF). General Estimate Equation modelling explored moderation effects of baseline markers and exploratory analyses investigated associations between markers and clinical outcomes. There was no difference between adjunctive minocycline or placebo groups at baseline or week 12 in the levels of IL-6 (week 12; placebo 2.06 ± 1.35 pg/ml; minocycline 1.77 ± 0.79 pg/ml; p = 0.317), LBP (week 12; placebo 3.74 ± 0.95 µg/ml; minocycline 3.93 ± 1.33 µg/ml; p = 0.525) or BDNF (week 12; placebo 24.28 ± 6.69 ng/ml; minocycline 26.56 ± 5.45 ng/ml; p = 0.161). Higher IL-6 levels at baseline were a predictor of greater clinical improvement. Exploratory analyses suggested that the change in IL-6 levels were significantly associated with anxiety symptoms (HAMA; p = 0.021) and quality of life (Q-LES-Q-SF; p = 0.023) scale scores. No other clinical outcomes were shown to have this mediation effect, nor did the other markers (LBP or BDNF) moderate clinical outcomes. There were no overall changes in IL-6, LBP or BDNF following adjunctive minocycline treatment. Exploratory analyses suggest a potential role of IL-6 on mediating anxiety symptoms with MDD. Future trials may consider enrichment of recruitment by identifying several markers or a panel of factors to better represent an inflammatory phenotype in MDD with larger sample size.

Mindfulness-based online intervention to improve quality of life in late-stage bipolar disorder: A randomized clinical trial.

Objective: Adjunctive psychological interventions improve outcomes in bipolar disorder (BD), but people in latter stages likely have different clinical needs. The objective here was to test the hypothesis that for people with ≥10 episodes of BD, a brief online mindfulness-based intervention (ORBIT 2.0) improves quality of life (QoL) relative to a Psychoeducation control. Method: A rater-masked, pragmatic superiority randomized clinical trial compared ORBIT 2.0 with active control. Both interventions were 5-week coach-supported programs with treatment as usual continued. Inclusion criteria included age 18-65 years, confirmed diagnosis of BD, and history of ≥10 episodes. Measures were collected at baseline, postintervention, and 3- and 6-month follow-ups. The main outcome was QoL, measured on the Brief Quality of Life in Bipolar Disorder (Brief QoL.BD) at 5 weeks, using intention-to-treat analyses. Results: Among N = 302 randomized participants, the primary hypothesis was not supported (Treatment × Time ß = -0.69, 95% CI [-2.69, 1.31], p = .50). The main effect of Time was not significant in either condition, indicating no improvement in either group. Recruitment was feasible, the platform was safe, both interventions were highly acceptable, but usage was suboptimal. Post hoc analyses found both interventions effective for participants not in remission from depression at baseline. Conclusions: In people with late-stage BD, an online mindfulness-based intervention was not superior to psychoeducational control in improving QoL. Online delivery was found to be safe and acceptable. Future interventions may need to be higher intensity, address engagement challenges, and target more symptomatic individuals. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

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.

Minocycline for the treatment of mental health and neurological conditions: study protocol of a systematic review and meta-analysis.

INTRODUCTION: Due to the anti-inflammatory, antioxidant and anti-apoptotic properties of minocycline, clinical trials have evaluated the potential of this drug to treat several psychiatric and neurological disorders, including major depressive disorder, schizophrenia, bipolar disorder, stroke and amyotrophic lateral sclerosis. This protocol proposes a systematic review (and potential meta-analysis) that aims to identify and critically evaluate randomised controlled trials of minocycline for treating psychiatric and neurological disorders. METHODS AND ANALYSIS: PubMed, Embase, Cochrane Central Register of Controlled Clinical Trials, PsycINFO and Cumulative Index to Nursing and Allied Health Literature (CINAHL) will be used to identify randomised controlled trials that used minocycline to treat psychiatric and neurological disorders. Double-blind, randomised, controlled, clinical trials of participants aged 18 years or older and written in English will be included in the review. Data will be extracted by two independent reviewers. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines will be followed and the Cochrane Collaboration's 'Risk of Bias' tool will be used to assess the risk of bias in all studies included in the systematic review. The Grading of Recommendations, Assessment, Development and Evaluation system will be used to access the overall quality of the level of evidence of the studies. If sufficient evidence is identified, a meta-analysis will be conducted using the standardised mean difference approach and reported with 95% CIs. Heterogeneity of evidence will be evaluated using the I2 model. ETHICS AND DISSEMINATION: This systematic review will evaluate only published data; therefore, ethical approval is not required. The systematic review will be published in a peer-reviewed journal and presented at relevant research conferences. TRIAL REGISTRATION NUMBER: CRD42020153292.

Personality disorder and functioning in major depressive disorder: a nested study within a randomized controlled trial

Objective: This study aimed to determine if personality disorder (PD) predicted functional outcomes in patients with major depressive disorder (MDD). Methods: Data (n=71) from a double-blind, randomized, placebo-controlled 12-week trial assessing the efficacy of 200 mg/day adjunctive minocycline for MDD were examined. PD was measured using the Standardized Assessment of Personality Abbreviated Scale. Outcome measures included Clinical Global Impression - Improvement (CGI-I), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), Social and Occupational Functioning Scale (SOFAS), and Range of Impaired Functioning (RIFT). Analysis of covariance was used to examine the impact of PD (dichotomized factor [≥ 3] or continuous measure) on the outcome measures-treatment group correlation. Results: PD was identified in 69% of the sample. After adjusting for age, sex, and baseline scores for each of the outcome measures, there was no significant difference between participants with and without PD on week 12 scores for any of the outcome measures (all p > 0.14). Conclusion: In this secondary analysis of a primary efficacy study, PD was a common comorbidity among those with MDD, but was not a significant predictor of functional outcomes. This study adds to the limited literature on PD in randomized controlled trials for MDD. Clinical trial registration: ACTRN12612000283875.

Personality disorder and functioning in major depressive disorder: a nested study within a randomized controlled trial.

OBJECTIVE: This study aimed to determine if personality disorder (PD) predicted functional outcomes in patients with major depressive disorder (MDD). METHODS: Data (n=71) from a double-blind, randomized, placebo-controlled 12-week trial assessing the efficacy of 200 mg/day adjunctive minocycline for MDD were examined. PD was measured using the Standardized Assessment of Personality Abbreviated Scale. Outcome measures included Clinical Global Impression - Improvement (CGI-I), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), Social and Occupational Functioning Scale (SOFAS), and Range of Impaired Functioning (RIFT). Analysis of covariance was used to examine the impact of PD (dichotomized factor [≥ 3] or continuous measure) on the outcome measures-treatment group correlation. RESULTS: PD was identified in 69% of the sample. After adjusting for age, sex, and baseline scores for each of the outcome measures, there was no significant difference between participants with and without PD on week 12 scores for any of the outcome measures (all p > 0.14). CONCLUSION: In this secondary analysis of a primary efficacy study, PD was a common comorbidity among those with MDD, but was not a significant predictor of functional outcomes. This study adds to the limited literature on PD in randomized controlled trials for MDD. CLINICAL TRIAL REGISTRATION: ACTRN12612000283875.

A randomized controlled trial of MoodSwings 2.0: An internet-based self-management program for bipolar disorder.

OBJECTIVES: MoodSwings 2.0 is an online self-guided intervention for bipolar disorder that includes educational modules, interactive tools, and discussion forums. The primary aim of the study was to determine if participation in MoodSwings 2.0 would result in decreased symptoms of depression and mania compared to the control condition. Secondary aims were to identify improvements in core depression symptoms, quality of life, medication adherence, functioning, and time to relapse. METHODS: This was a three-arm randomized controlled trial that compared two intervention arms against a peer support control group (forum). A total of 304 adults aged 21 to 65 years with a diagnosis of bipolar disorder were assigned to a forum-only control group (Group 1; n = 102), a forum plus modules treatment group (Group 2; n = 102), or a forum, modules, and tools treatment group (Group 3; n = 100), in addition to usual care. RESULTS: There was a significant intervention impact showing improvement on the primary outcome of depression for Group 2 compared to Group 1 (P = .05) with effect sizes (Cohen's d) ranging from 0.17 to 0.43. There was also a significant intervention impact showing improvement on the secondary outcome of core depression for Group 2 (P = .02) and Group 3 (P = .05), but worse physical functioning for Group 3 (P = .01), compared to Group 1. CONCLUSIONS: This study provides evidence of the efficacy of internet-based psychoeducation interventions for bipolar disorder in reducing depressive symptoms. Further investigation is needed to assess effectiveness in a public program.

Mental health information online: what we have learned from social media metrics in BuzzFeed's Mental Health Week / Informações de saúde mental on-line: o que aprendemos com as métricas de mídias sociais na Semana de Saúde Mental do BuzzFeed

Abstract Introduction The Internet has seen rapid growth in the number of websites focusing on mental health content. Considering the increased need for access to accurate information about mental health treatment, it is important to understand the promotion of this information online. Objective To analyze BuzzFeed's Mental Health Week (BFMHW) interactions on its own website and in related social media platforms (Facebook, Twitter and YouTube) using metrics of information delivery in mental health topics. Methods We extracted social media metrics from the 20 posts with the highest number of BuzzFeed interactions on the BFMHW website and from 41 videos available on the BFMHW playlist created by the BuzzFeed Video profile on YouTube. We analyzed the format and content used in BuzzFeed's publishing methods as well as the following social media metrics: exposure (presence online, views and time online), influence (likes) and engagement (comments, shares, replies and BuzzFeed interactions). Results Analysis of the variables revealed that audience engagement is associated with the number of medias in which the content is published: views on YouTube and shares on Facebook (0.71, p<0.001), total interactions on Facebook (0.66, p<0.001) and BuzzFeed number of total interactions (0.56, p<0.001). Conclusions Our results suggest that videos on YouTube may be an important information channel, including activity and engagement on other medias such as Facebook. Information may be more effective in reaching the audience if it is delivered in more than one media and includes personal experiences, some humor in content and detailed information about treatment.

Resumo Introdução O número de sites com foco em conteúdo de saúde mental vem crescendo rapidamente. Considerando a necessidade crescente de acesso a informações precisas sobre tratamento em saúde mental, é importante entender a promoção dessas informações on-line. Objetivo Analisar as interações da Semana de Saúde Mental do BuzzFeed (BuzzFeed's Mental Health Week - BFMHW) em seu próprio site e em plataformas de mídia social relacionadas (Facebook, Twitter e YouTube) usando métricas de entrega de informações em tópicos de saúde mental. Métodos Extraímos métricas de mídias sociais das 20 postagens com o maior número de interações no site da BFMHW e de 41 vídeos disponíveis na playlist da BFMHW criada pelo perfil BuzzFeed Video no YouTube. Analisamos o formato e o conteúdo usados nos métodos de publicação do BuzzFeed, bem como as seguintes métricas de mídias sociais: exposição (presença on-line, visualizações e tempo on-line), influência (curtidas) e engajamento (comentários, compartilhamentos, respostas e interações do BuzzFeed). Resultados A análise das variáveis revelou que o envolvimento do público está associado ao número de mídias em que o conteúdo é publicado: visualizações no YouTube e compartilhamentos no Facebook (0,71, p <0,001), interações totais no Facebook (0,66, p <0,001) e número de interações totais no BuzzFeed (0,56, p <0,001). Conclusões Nossos resultados sugerem que o YouTube pode ser um importante canal de informações, incluindo atividades e envolvimento em outras mídias, como o Facebook. As informações podem alcançar o público de forma mais eficaz se forem exibidas em mais de uma mídia e incluírem experiências pessoais, algum humor no conteúdo e informações detalhadas sobre o tratamento.

Mental health information online: what we have learned from social media metrics in BuzzFeed's Mental Health Week.

INTRODUCTION: The Internet has seen rapid growth in the number of websites focusing on mental health content. Considering the increased need for access to accurate information about mental health treatment, it is important to understand the promotion of this information online. OBJECTIVE: To analyze BuzzFeed's Mental Health Week (BFMHW) interactions on its own website and in related social media platforms (Facebook, Twitter and YouTube) using metrics of information delivery in mental health topics. METHODS: We extracted social media metrics from the 20 posts with the highest number of BuzzFeed interactions on the BFMHW website and from 41 videos available on the BFMHW playlist created by the BuzzFeed Video profile on YouTube. We analyzed the format and content used in BuzzFeed's publishing methods as well as the following social media metrics: exposure (presence online, views and time online), influence (likes) and engagement (comments, shares, replies and BuzzFeed interactions). RESULTS: Analysis of the variables revealed that audience engagement is associated with the number of medias in which the content is published: views on YouTube and shares on Facebook (0.71, p<0.001), total interactions on Facebook (0.66, p<0.001) and BuzzFeed number of total interactions (0.56, p<0.001). CONCLUSIONS: Our results suggest that videos on YouTube may be an important information channel, including activity and engagement on other medias such as Facebook. Information may be more effective in reaching the audience if it is delivered in more than one media and includes personal experiences, some humor in content and detailed information about treatment.

Web-based intervention to improve quality of life in late stage bipolar disorder (ORBIT): randomised controlled trial protocol.

BACKGROUND: The primary objective of this randomised controlled trial (RCT) is to establish the effectiveness of a novel online quality of life (QoL) intervention tailored for people with late stage (≥ 10 episodes) bipolar disorder (BD) compared with psychoeducation. Relative to early stage individuals, this late stage group may not benefit as much from existing psychosocial treatments. The intervention is a guided self-help, mindfulness based intervention (MBI) developed in consultation with consumers, designed specifically for web-based delivery, with email coaching support. METHODS/DESIGN: This international RCT will involve a comparison of the effectiveness and cost-effectiveness of two 5-week adjunctive online self-management interventions: Mindfulness for Bipolar 2.0 and an active control (Psychoeducation for Bipolar). A total of 300 participants will be recruited primarily via social media channels. Main inclusion criteria are: a diagnosis of BD (confirmed via a phone-administered structured diagnostic interview), no current mood episode, history of 10 or more mood episodes, no current psychotic features or active suicidality, under the care of a medical practitioner. Block randomisation will be used for allocation to the interventions, and participants will retain access to the program for 6 months. Evaluations will be conducted at pre- and post- treatment, and at 3- and 6- months follow-up. The primary outcome measure will be the Brief Quality of Life in Bipolar Disorder Scale (Brief QoL.BD), collected immediately post-intervention at 5 weeks (T1). Secondary measures include BD-related symptoms (mania, depression, anxiety, stress), time to first relapse, functioning, sleep quality, social rhythm stability and resource use. Measurements will be collected online and via telephone assessments at baseline (T0), 5 weeks (T1), three months (T2) and six months (T3). Candidate moderators (diagnosis, anxiety or substance comorbidities, demographics and current treatments) will be investigated as will putative therapeutic mechanisms including mindfulness, emotion regulation and self-compassion. A cost-effectiveness analysis will be conducted. Acceptability and any unwanted events (including adverse treatment reactions) will be documented and explored. DISCUSSION: This definitive trial will test the effectiveness and cost-effectiveness of a novel QoL focused, mindfulness based, online guided self-help intervention for late stage BD, and investigate its putative mechanisms of therapeutic action. TRIAL REGISTRATION: ClinicalTrials.gov : NCT03197974 . Registered 23 June 2017.

Staging in bipolar disorder: from theoretical framework to clinical utility.

Illness staging is widely utilized in several medical disciplines to help predict course or prognosis, and optimize treatment. Staging models in psychiatry in general, and bipolar disorder in particular, depend on the premise that psychopathology moves along a predictable path: an at-risk or latency stage, a prodrome progressing to a first clinical threshold episode, and one or more recurrences with the potential to revert or progress to late or end-stage manifestations. The utility and validity of a staging model for bipolar disorder depend on its linking to clinical outcome, treatment response and neurobiological measures. These include progressive biochemical, neuroimaging and cognitive changes, and potentially stage-specific differences in response to pharmacological and psychosocial treatments. Mechanistically, staging models imply the presence of an active disease process that, if not remediated, can lead to neuroprogression, a more malignant disease course and functional deterioration. Biological elements thought to be operative in bipolar disorder include a genetic diathesis, physical and psychic trauma, epigenetic changes, altered neurogenesis and apoptosis, mitochondrial dysfunction, inflammation, and oxidative stress. Many available agents, such as lithium, have effects on these targets. Staging models also suggest the utility of stage-specific treatment approaches that may not only target symptom reduction, but also impede illness neuroprogression. These treatment approaches range from prevention for at-risk individuals, to early intervention strategies for prodromal and newly diagnosed individuals, complex combination therapy for rapidly recurrent illness, and palliative-type approaches for those at chronic, late stages of illness. There is hope that prompt initiation of potentially disease modifying therapies may preclude or attenuate the cognitive and structural changes seen in the later stages of bipolar disorder. The aims of this paper are to: a) explore the current level of evidence supporting the descriptive staging of the syndromal pattern of bipolar disorder; b) describe preliminary attempts at validation; c) make recommendations for the direction of further studies; and d) provide a distillation of the potential clinical implications of staging in bipolar disorder within a broader transdiagnostic framework.

Adjunctive minocycline treatment for major depressive disorder: A proof of concept trial.

OBJECTIVE: Conventional antidepressant treatments result in symptom remission in 30% of those treated for major depressive disorder, raising the need for effective adjunctive therapies. Inflammation has an established role in the pathophysiology of major depressive disorder, and minocycline has been shown to modify the immune-inflammatory processes and also reduce oxidative stress and promote neuronal growth. This double-blind, randomised, placebo-controlled trial examined adjunctive minocycline (200 mg/day, in addition to treatment as usual) for major depressive disorder. This double-blind, randomised, placebo-controlled trial investigated 200 mg/day adjunctive minocycline (in addition to treatment as usual) for major depressive disorder. METHODS: A total of 71 adults with major depressive disorder ( Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition) were randomised to this 12-week trial. Outcome measures included the Montgomery-Asberg Depression Rating Scale (primary outcome), Clinical Global Impression-Improvement and Clinical Global Impression-Severity, Hamilton Anxiety Rating Scale, Quality of Life Enjoyment and Satisfaction Questionnaire, Social and Occupational Functioning Scale and the Range of Impaired Functioning Tool. The study was registered on the Australian and New Zealand Clinical Trials Register: www.anzctr.org.au , #ACTRN12612000283875. RESULTS: Based on mixed-methods repeated measures analysis of variance at week 12, there was no significant difference in Montgomery-Asberg Depression Rating Scale scores between groups. However, there were significant differences, favouring the minocycline group at week 12 for Clinical Global Impression-Improvement score - effect size (95% confidence interval) = -0.62 [-1.8, -0.3], p = 0.02; Quality of Life Enjoyment and Satisfaction Questionnaire score - effect size (confidence interval) = -0.12 [0.0, 0.2], p < 0.001; and Social and Occupational Functioning Scale and the Range of Impaired Functioning Tool score - 0.79 [-4.5, -1.4], p < 0.001. These effects remained at follow-up (week 16), and Patient Global Impression also became significant, effect size (confidence interval) = 0.57 [-1.7, -0.4], p = 0.017. CONCLUSION: While the primary outcome was not significant, the improvements in other comprehensive clinical measures suggest that minocycline may be a useful adjunct to improve global experience, functioning and quality of life in people with major depressive disorder. Further studies are warranted to confirm the potential of this accessible agent to optimise treatment outcomes.