The Resistant Depression Response to Esketamine Assessing Metabolomics (ReDREAM) Project-Untargeted Metabolomics to Identify Biomarkers of Treatment Response to Intranasal Esketamine in Individuals with Treatment-Resistant Depression: A Study Protocol.

Objective: Treatment-resistant depression (TRD) affects around 20-30% of people with major depressive disorder. In 2019, esketamine nasal spray was approved for TRD by both the US Food and Drug Administration and the European Medicines Agency. While its clinical efficacy and safety are proven, the mechanisms underlying its antidepressant effect remain unclear. The use of metabolomics may allow understanding the metabolic effects of esketamine and predicting biological features associated with clinical response in TRD. Nonetheless, there is a lack of studies exploring the predictive value of metabolomics. The Resistant Depression Response to Esketamine Assessing Metabolomics (ReDREAM) project aims at identifying metabolic biosignatures that may represent novel correlates of response to esketamine treatment. Study Design: This is the protocol of an observational, prospective study. Methods: We plan to select 60 people with TRD from 3 clinical sites in Italy. The participants will be administered with esketamine nasal spray, following standard clinical practice, twice a week for 4 weeks ("induction phase"), then once a week for 4 additional weeks ("maintenance phase"). We will test the correlations between baseline metabolic profile and depressive symptom improvement at study endpoints (weeks 4 and 8) and we will explore the likelihood of different metabolic phenotypes between responders and non-responders. Expected results: An involvement of energy metabolism, amino acid metabolism, urea cycle, and nitric oxide synthesis in response to treatment with esketamine nasal spray is hypothesized. Conclusion: Unbiased data from untargeted metabolomics associated with clinical changes after esketamine treatment may contribute to define new paradigms for precision psychiatry-oriented, personalized care of TRD.

Anti-obesity Drugs for the Treatment of Binge Eating Disorder: Opportunities and Challenges.

Binge eating disorder (BED) is the most prevalent form of disordered eating, frequently associated with obesity. Both these conditions along with sharing overeating behaviour features can lead to substantial burden of disease and premature mortality. With limited specific evidence available on pharmacotherapy, since lisdexamfetamine is approved only in some countries, new drugs are urgently needed to provide physicians with efficacious prescribing choices when treating BED. Although unique mechanisms underlie psychopathological features of binge eating, including impulsivity, compulsivity, and emotional reactivity, anti-obesity drugs might represent an option for both weight management and symptom reduction in people with BED. The aim of this review is thus to provide a summary of available evidence on the efficacy of anti-obesity drugs for BED. After comprehensively searching for relevant studies in PubMed and the Cochrane Library, as well as for unpublished results in ClinicalTrials.gov, we included 14 clinical trials. Despite the limited sample size and the methodological variability, evidence from available studies suggests that most anti-obesity drugs, namely phentermine/topiramate, naltrexone/bupropion, liraglutide and semaglutide, though not orlistat, might variously achieve improvements for both body weight and severity and frequency of binge episodes. Findings from ongoing clinical trials are likely to provide further insight into the possible role of anti-obesity drugs for treating BED. Since these agents can hold the potential to be misused potentiating dietary restriction and pathological weight loss, it is crucial to promote responsible prescribing practices.

Understanding University Students' Perspectives towards Digital Tools for Mental Health Support: A Cross-country Study.

Background: Organisational and individual barriers often prevent university students from seeking mental health support. Digital technologies are recognised as effective in managing psychological distress and as a source of health-related information, thus representing useful options to address mental health needs in terms of accessibility and cost-effectiveness. However, university students' experiences and perspectives towards such interventions are little known. Objectives: We thus aimed to expand the existing base of scientific knowledge, focusing on this special population. Methods: Data were from the qualitative component of "the CAMPUS study", longitudinally assessing the mental health of students at the University of Milano-Bicocca (Italy) and the University of Surrey (UK). We conducted in-depth interviews and thematically analysed the transcripts using the framework approach. Results: An explanatory model was derived from five themes identified across 33 interviews (15 for Italy, 18 for the UK). Students perceived that social media, apps, and podcasts could deliver relevant mental health content, ranging from primary to tertiary prevention. Wide availability and anonymity were perceived as advantages that make tools suitable for preventive interventions, to reduce mental health stigma, and as an extension of standard treatment. These goals can be hindered by disadvantages, namely lower efficacy compared to face-to-face contact, lack of personalisation, and problematic engagement. Individual and cultural specificities might influence awareness and perspectives on the use of digital technologies for mental health support. Conclusion: Although considering some specific features, digital tools could be a useful instrument to support the mental health needs of students. Since personal contact remains crucial, digital tools should be integrated with face-to-face interventions through a multi-modal approach.

Evidence from preclinical and clinical metabolomics studies on the antidepressant effects of ketamine and esketamine.

The antidepressant effects of ketamine and esketamine are well-documented. Nonetheless, most of the underlying molecular mechanisms have to be uncovered yet. In the last decade, metabolomics has emerged as a useful means to investigate the metabolic phenotype associated with depression as well as changes induced by antidepressant treatments. This mini-review aims at summarizing the main findings from preclinical and clinical studies that used metabolomics to investigate the metabolic effects of subanesthetic, antidepressant doses of ketamine and esketamine and their relationship with clinical response. Both animal and human studies report alterations in several metabolic pathways - including the tricarboxylic acid cycle, glycolysis, the pentose phosphate pathway, lipid metabolism, amino acid metabolism, the kynurenine pathway, and the urea cycle - following the administration of ketamine or its enantiomers. Although more research is needed to clarify commonalities and differences in molecular mechanisms of action between the racemic compound and its enantiomers, these findings comprehensively support an influence of ketamine and esketamine on mitochondrial and cellular energy production, membrane homeostasis, neurotransmission, and signaling. Metabolomics may thus represent a promising strategy to clarify molecular mechanisms underlying treatment-resistant depression and related markers of clinical response to ketamine and esketamine. This body of preclinical and clinical evidence, if further substantiated, has the potential to guide clinicians towards personalized approaches, contributing to new paradigms in the clinical management of depression.

Long-acting injectable antipsychotics for the treatment of bipolar disorder: evidence from mirror-image studies.

Clinical trials and real-world data have shown that long-acting injectable antipsychotics (LAIs) might be an effective therapeutic option also for people with bipolar disorder (BD). However, complementing evidence from mirror-image studies investigating LAIs in BD is scattered and has not been systematically evaluated so far. We thus performed a review of observational mirror-image studies testing the effectiveness of LAI treatment on clinical outcomes in people with BD. Embase, MEDLINE, and PsycInfo electronic databases were systematically searched (via Ovid) up to November 2022. We included six mirror-image studies that compared relevant clinical outcomes between the 12-months after (post-treatment period) and the 12-months before (pre-treatment period) the initiation of a LAI treatment in adults with BD. We found that LAI treatment is associated with a significant reduction in days spent in hospital and number of hospitalizations. Moreover, LAI treatment seems to be associated with a significant decrease in the proportion of individuals with at least one hospital admission, even though data on this outcome were reported by just two studies. In addition, studies consistently estimated a significant reduction of hypo-/manic relapses after LAI treatment initiation, while the effect of LAIs for depressive episodes is less clear. Finally, LAI treatment initiation was associated with a lower number of emergency department visits in the year after LAI initiation. The findings of this review seem to suggest that the use of LAIs is an effective strategy to improve major clinical outcomes in people with BD. Nonetheless, additional research, based on standardized assessments of prevalent polarity and relapses, is needed to identify the clinical characteristics of individuals with BD who are most likely to benefit from a LAI treatment.

Mental Health and COVID-19 in University Students: Findings from a Qualitative, Comparative Study in Italy and the UK.

INTRODUCTION: COVID-19 restrictions introduced several changes in university academic and social experience. Self-isolation and online teaching have amplified students' mental health vulnerability. Thus, we aimed to explore feelings and perspectives about the impact of the pandemic on mental health, comparing students from Italy and the UK. METHODS: Data were collected from the qualitative portion of "the CAMPUS study", longitudinally assessing mental health of students at the University of Milano-Bicocca (Italy) and the University of Surrey (UK). We conducted in-depth interviews and thematically analysed the transcripts. RESULTS: The explanatory model was developed from four themes identified across 33 interviews: anxiety exacerbated by COVID-19; putative mechanisms leading to poor mental health; the most vulnerable subgroups; and coping strategies. Generalised and social anxiety resulted from COVID-19 restrictions by being associated with loneliness, excessive time online, unhealthy management of time and space and poor communication with the university. Freshers, international students, and people on the extremes of the introversion/extroversion spectrum, were identified as vulnerable, while effective coping strategies included taking advantage of free time, connection with family and mental health support. The impact of COVID-19 was mostly related to academic issues by students from Italy, whereas to the drastic loss of social connectedness by the UK sample. CONCLUSIONS: Mental health support for students has an essential role, and measures that encourage communication and social connectedness are likely to be beneficial.

Effect of long-acting injectable antipsychotics on 1-year hospitalization in bipolar disorder: a mirror-image study.

Long-acting injectable (LAI) antipsychotics are often used for the long-term management also of bipolar disorder (BD). Nonetheless, evidence on their effect on pragmatic outcomes such as hospitalization risk in BD is inconsistent. We carried out a mirror-image study comparing rates and number of days of hospitalization, one year before and after the initiation of LAI treatment, in a sample of subjects with BD. Participants were selected from the STAR Network Depot Study, a pragmatic, observational, multicenter research involving a cohort of inpatients and outpatients consecutively started on LAI treatment. Variations in rates and in total number of days of hospitalization between the 12 months before and those after treatment initiation were analyzed. Among 461 individuals screened for eligibility, we included 71 adults with BD, initiated either on first- (FGA) or second-generation (SGA) LAIs. We found a significant decrease in terms of 12-month hospitalization rates (p < 0.001) and number of days (p < 0.001) after LAI initiation, without any effect by age, gender, alcohol/substance use disorders, and symptom severity. Subgroup analyses based on antipsychotic class, history of LAI treatment, and concomitant oral medications, confirmed the decreasing trend on both hospitalization rates and number of days. However, these reductions were not significant among participants who continued this treatment for less than 6 months. Comprehensively, this study supports the role of LAIs as effective maintenance treatment options for BD. Further research is needed to identify clinical characteristics of people with BD who would most benefit from long-acting formulations of antipsychotics.

Clinical correlates of comorbid attention deficit hyperactivity disorder in adults suffering from bipolar disorder: A meta-analysis.

OBJECTIVE: Attention deficit hyperactivity disorder is a frequent comorbid condition in adults with bipolar disorder. We performed a meta-analysis aimed at assessing sociodemographic and clinical correlates of attention deficit hyperactivity disorder in bipolar disorder. METHOD: We searched main electronic databases up to June 2021. Random-effects meta-analyses, with relevant meta-regression and quality-based sensitivity analyses, were carried out to estimate the association between attention deficit hyperactivity disorder and putative correlates, grading the quality of evidence. RESULTS: We included 43 studies, based on 38 independent samples. Attention deficit hyperactivity disorder participants were more likely to be males (odds ratio = 1.46; p < 0.001) and unemployed (odds ratio = 1.45; p = 0.045), and less likely to be married (odds ratio = 0.62; p = 0.014). They had an earlier onset of bipolar disorder (standardized mean difference = -0.36; p < 0.001); more mood episodes (standardized mean difference = 0.35; p = 0.007), particularly depressive (standardized mean difference = 0.30; p = 0.011) and mixed (standardized mean difference = 0.30; p = 0.031) ones; higher odds of using antidepressants (odds ratio = 1.80; p = 0.024) and attempted suicides (odds ratio = 1.83; p < 0.001) and lower odds of psychotic features (odds ratio = 0.63; p = 0.010). Moreover, they were more likely to have generalized anxiety disorder (odds ratio = 1.50; p = 0.019), panic disorder (odds ratio = 1.89; p < 0.001), social phobia (odds ratio = 1.61; p = 0.017), eating disorders (odds ratio = 1.91; p = 0.007), antisocial personality disorder (odds ratio = 3.59; p = 0.004) and substance (odds ratio = 2.29; p < 0.001) or alcohol (odds ratio = 2.28; p < 0.001) use disorders. Quality of the evidence was generally low or very low for the majority of correlates, except for bipolar disorder onset and alcohol/substance use disorders (high), and suicide attempts (moderate). CONCLUSION: Comorbid bipolar disorder/attention deficit hyperactivity disorder may have some distinctive clinical features including an earlier onset of bipolar disorder and higher comorbid alcohol/substance use disorder rates. Further research is needed to identify additional clinical characteristics of this comorbidity.

Forcibly displaced persons and mental health: A survey of the experiences of Europe-wide psychiatry trainees during their training.

Many European countries have seen increasing refugee populations and asylum applications over the past decade. Forcibly displaced persons (FDPs) are known to be at higher risk of developing mental disorders and are in need of specific care. Thus, specific training for mental health professionals is recommended by international health organizations. The aim of this exploratory study was to assess the experience of clinical work with FDPs among psychiatric trainees in Europe and Central Asia as well as their interest and specific training received on this topic. An online questionnaire was designed by the Psychiatry Across Borders working group of the European Federation of Psychiatric Trainees (EFPT) and was distributed via email through local networks among European trainees from 47 countries between March 2017 and April 2019. Answers of 342 psychiatric trainees from 15 countries were included in the survey analysis. A majority of trainees (71%) had had contact with FDPs in the last year of their clinical work. Although three-quarters expressed a strong interest in the mental health of FDPs, only 35% felt confident in assessing and treating them. Specific training was provided to 25% of trainees; of this subset, only a quarter felt this training prepared them adequately. Skills training on transcultural competencies, post-traumatic stress disorder, and trauma management was regarded as essential to caring for refugees with confidence. Although psychiatric trainees are motivated to improve their skills in treating FDPs, a lack of adequate specific training has been identified. The development of practical skills training is essential. International online training courses could help meet this pressing need.

Digital mental health interventions for anxiety and depressive symptoms in university students during the COVID-19 pandemic: A systematic review of randomized controlled trials.

University students are particularly vulnerable to mental health issues, with anxiety and depression identified as the most common conditions. During the COVID-19 pandemic, social distancing, self-isolation, and difficulties linked to online teaching and learning have increased their burden of anxiety and depressive symptoms. Thus, the urgent need to intervene in favour of these vulnerable subjects, together with the difficulties in delivering in-person interventions because of lockdowns and restrictions, has led to prioritize digital mental health strategies. This study aimed at systematically reviewing the existing literature on digital mental health interventions targeting anxiety and depressive symptoms in university students during the COVID-19 emergency. Systematic searches of Medline, Embase, and PsycInfo databases identified eight randomized controlled trials. Regarding anxiety symptoms, digitally delivered cognitive behavioural therapy, dialectical behaviour therapy, and mind-body practice techniques emerged as valid strategies, while digital positive psychology and mindfulness-based interventions showed mixed results. On the other hand, digitally delivered dialectical behaviour therapy and positive psychology interventions have shown some efficacy in reducing depressive symptoms. Overall, the available literature, albeit of low quality, seems to support the role of digital interventions in promoting the mental health of university students during the COVID-19 pandemic.

Los estudiantes universitarios son particularmente vulnerables a los problemas de salud mental, siendo la ansiedad y la depresión las condiciones más comunes. Durante la pandemia de COVID-19, el distanciamiento social, el autoaislamiento y las dificultades relacionadas con la enseñanza y el aprendizaje en línea han aumentado su carga de ansiedad y síntomas depresivos. Así, la urgente necesidad de intervenir a favor de estos sujetos vulnerables, junto con las dificultades para realizar intervenciones presenciales a causa de los confinamientos y restricciones, ha llevado a priorizar estrategias de salud mental digital. Este estudio tuvo como objetivo revisar sistemáticamente la literatura existente sobre intervenciones digitales de salud mental dirigidas a la ansiedad y los síntomas depresivos en estudiantes universitarios durante la emergencia de COVID-19. Las búsquedas sistemáticas en las bases de datos Medline, Embase y PsycInfo identificaron ocho ensayos controlados aleatorios. Con respecto a los síntomas de ansiedad, la terapia cognitiva conductual, la terapia conductual dialéctica y las técnicas de práctica mente-cuerpo entregadas digitalmente surgieron como estrategias válidas, mientras que la psicología positiva digital y las intervenciones basadas en el mindfulness mostraron resultados mixtos. Por otro lado, la terapia conductual dialéctica y las intervenciones de psicología positiva proporcionadas digitalmente han demostrado cierta eficacia en la reducción de los síntomas depresivos. En general, la literatura disponible, aunque de baja calidad, parece respaldar el papel de las intervenciones digitales en la promoción de la salud mental de los estudiantes universitarios durante la pandemia de COVID-19.

Blood concentrations of neopterin and biopterin in subjects with depression: A systematic review and meta-analysis.

INTRODUCTION: Pteridines, such as neopterin, biopterin, and tetrahydrobiopterin (BH4), may be involved in depression pathophysiology owing to their links to immune-inflammatory response, oxidative and nitrosative stress, and monoaminergic transmission. Nonetheless, studies assessing pteridines in depression are inconsistent. We conducted a systematic review and meta-analysis of observational studies comparing blood pteridine concentrations between subjects with depression and healthy controls (HCs). METHODS: We searched Embase, MEDLINE, and PsycInfo for articles indexed through November 2021. Study quality was appraised, evaluating age and gender comparability between groups, sample representativeness, and methods to assess depression. Random-effects meta-analyses were carried out, generating pooled standardized mean differences (SMDs). Heterogeneity across studies was estimated using the I2 statistic. RESULTS: Twenty-four studies, involving 3075 subjects, were included. Individuals with depression showed blood neopterin concentrations higher than HCs (k = 19; SMD = 0.36; p < 0.001) with moderate heterogeneity across studies (I2 = 58.2%). No moderating role of age, gender, or type of blood sample was found. Sensitivity analyses showed no impact of inconsistency and quality of studies on findings. Neopterin concentrations were higher among individuals with major depressive disorder compared to HCs (SMD = 0.44; p < 0.001). This held true also when considering only drug-free subjects (SMD = 0.68; p = 0.003). No differences in biopterin concentrations were found between subjects with depression and HCs (k = 5; SMD = -0.35; p = 0.086), though this result was limited by inconsistency of findings (I2 = 77.9%) and quality of studies. Finally, no sufficient data were available for a meta-analysis on BH4. CONCLUSIONS: As a whole, our work partly supports the hypothesis of an imbalance of pteridine metabolism in depression.

Testing the Impact of Depressive and Anxiety Features on the Association between Attention-Deficit/Hyperactivity Disorder Symptoms and Academic Performance among University Students: A Mediation Analysis.

Attention deficit/hyperactivity disorder (ADHD) is associated with poor academic performance also among university students. This relationship may be made more complex by comorbid conditions. The aim of this study was to evaluate the mediating role of anxiety and depressive symptoms in the relationship between ADHD and academic performance. Data were drawn from the CAMPUS study (registration number: 0058642/21), an ongoing survey on university students' mental health. Using a logit model, mediation analyses were carried out to test whether the relationship between ADHD symptoms (assessed by ASRS-5) and academic performance might be mediated by depressive (assessed by PHQ-9) and anxiety (assessed by GAD-7) symptoms. Our results showed that worse academic performance is associated with ADHD symptoms (p < 0.001). However, about 24% of the overall association between ADHD symptoms and academic performance was mediated by depressive symptoms (indirect effect: 0.065, 95%CI 0.022; 0.100), whereas the contribution of anxiety symptoms to the model was not significant. Along with the association between ADHD symptoms and poor academic performance, our findings highlight the key mediating role of depressive symptoms, which may be targeted with tailored support, ultimately improving both the academic performance and the well-being of university students with ADHD.

Were anxiety, depression and psychological distress associated with local mortality rates during COVID-19 outbreak in Italy? Findings from the COMET study.

BACKGROUND: The mental health of the Italian population declined at the onset of the COVID-19 pandemic. However, nationwide population prevalence estimates may not effectively reproduce the heterogeneity in distress responses to the pandemic. In particular, contextual determinants specific to COVID-19 pandemic need to be considered. We thus aimed to explore the association between local COVID-19 mortality rates and mental health response among the general population. METHODS: We capitalised on data (N = 17,628) from a large, cross-sectional, national survey, the COMET study, run between March and May 2020. While psychological distress was measured by General Health Questionnaire-12 (GHQ-12), the Depression, Anxiety and Stress Scale-21 Items (DASS-21) was used to assess relevant domains. In addition, a Covid-19 mortality ratio was built to compare single regional mortality rates to the national estimate and official statistics were used to control for other area-level determinants. RESULTS: Adjusted ordered regression analyses showed an association between mortality ratio and moderate (OR = 1.10, 95%CI 1.03-1.18) and severe (OR = 1.11, 95%CI 1.03-1.21) DASS-21 anxiety levels. No effects of mortality ratio on GHQ-12 scores and DASS-21 depression and stress levels, uniformly high across the country, were estimated. CONCLUSIONS: Although we could not find any association between regional COVID-19 mortality ratio and depression or psychological distress, anxiety levels were significantly increased among subjects from areas with the highest mortality rates. Local mortality rate seems a meaningful driver for anxiety among the general population. Considering the potentially long-lasting scenario, local public health authorities should provide neighbouring communities with preventive interventions reducing psychological isolation and anxiety levels.

Professionals' Digital Training for Child Maltreatment Prevention in the COVID-19 Era: A Pan-European Model.

The responsiveness of professionals working with children and families is of key importance for child maltreatment early identification. However, this might be undermined when multifaceted circumstances, such as the COVID-19 pandemic, reduce interdisciplinary educational activities. Thanks to technological developments, digital platforms seem promising in dealing with new challenges for professionals' training. We examined a digital approach to child maltreatment training through the ERICA project experience (Stopping Child Maltreatment through Pan-European Multiprofessional Training Programme). ERICA has been piloted during the pandemic in seven European centers involving interconnected sectors of professionals working with children and families. The training consisted of interactive modules embedded in a digital learning framework. Different aspects (technology, interaction, and organization) were evaluated and trainers' feedback on digital features was sought. Technical issues were the main barrier, however, these did not significantly disrupt the training. The trainers perceived reduced interaction between participants, although distinct factors were uncovered as potential favorable mediators. Based on participants' subjective experiences and perspectives, digital learning frameworks for professionals working with children and families (such as the ERICA model nested in its indispensable adaptation to an e-learning mode) can represent a novel interactive approach to empower trainers and trainees to tackle child maltreatment during critical times such as a pandemic, and as an alternative to more traditional learning frameworks.

Comparing 1-year effectiveness and acceptability of once-monthly paliperidone palmitate and aripiprazole monohydrate for schizophrenia spectrum disorders: Findings from the STAR Network Depot Study.

In this prospective study, we assessed the effectiveness and acceptability of paliperidone palmitate 1-month (PP1M) and aripiprazole monohydrate (AM) over 1-year follow-up. We included 195 subjects (117 treated with PP1M and 78 with AM) with schizophrenia spectrum disorders from real-world settings. We estimated no differences in hospitalization (Odds Ratio=1.59; p = 0.12), symptoms improvement (p = 0.90 adjusted for baseline severity), and discontinuation (Hazard Ratio=0.72; p = 0.20) at study endpoint. Although current evidence suggests the possible superiority of AM over PP1M, our findings showed comparable effectiveness between these drugs. Additional studies in real-world settings with direct comparisons between these two LAIs are needed.

Practical Guidance for the Use of Long-Acting Injectable Antipsychotics in the Treatment of Schizophrenia.

Schizophrenia is a severe mental illness causing a high degree of disability. First- and second-generation antipsychotics (FGAs and SGAs) represent key resources for its acute and long-term management. Since a poor adherence to oral treatments may negatively impact the course of the disorder, long-acting injectable antipsychotics (LAIs) are often used to reduce clinical relapses. Notwithstanding their potential beneficial features, LAIs use in clinical practice remains somewhat hampered by the limited amount of relevant systematic information. This review thus aims at providing a clinical, practical guidance for the use of LAIs in the treatment of schizophrenia. We synthetized main information on indications, dosage, and administration of LAIs approved by the US Food and Drug Administration (FDA) and/or in EU countries, as well as evidence from the most recent systematic reviews and meta-analyses. Currently available information, though heterogeneous, shows that LAIs can prevent relapses and rehospitalizations, improving clinical outcomes and favouring sustained remission among people with schizophrenia. The use of SGA LAIs is supported by more robust evidence than FGA LAIs. Along with their positive impact on the prevention of treatment discontinuation, some LAIs might also enhance individual global functioning and quality of life, without additional adverse events or health-care costs, as compared with oral antipsychotics. Although which LAIs can be considered a first-choice option, as well as their superiority over oral antipsychotics, remain unclear issues, this review offers a comprehensive overview of information available on the use of LAIs for people with schizophrenia, providing clinicians with practical guidance in terms of efficacy and acceptability of single agents. Literature gaps and future research needs are also described.

Innovations in community-based mental health care: an overview of meta-analyses.

In the last four decades, mental health services for people with Severe Mental Illness (SMI) have seen asylums replaced by a balanced model of Community Mental Healthcare (CMH). Innovative approaches and strategies in the field of CMH have been extensively researched. However, this research has been hampered by issues limiting their capacity to inform clinicians and policymakers. We conducted an overview of meta-analyses of the effectiveness of innovative CMH models focussing on clinical and psychosocial outcomes in comparisons with standard care in adults with SMI. Based on the 12 eligible studies, we appraised, synthesised and graded the resulting evidence. There was moderate quality evidence that case management, Early Intervention Services (EIS) and caregiver-directed interventions were superior to standard care in reducing hospital admission. In relation to psychosocial outcomes, EIS showed high quality evidence of a small effect on global functioning. There was moderate quality evidence for a similar effect of Intensive Case Management, and for a large effect of family intervention. For quality of life, both EIS and self-management education had a small effect, with moderate quality. The level of research about effective CMH models is therefore substantial. However, several gaps related to innovative CMH not yet covered in meta-analytic synthesis, need to be filled.

Repurposed drugs as adjunctive treatments for mania and bipolar depression: A meta-review and critical appraisal of meta-analyses of randomized placebo-controlled trials.

Several drugs previously tested in clinical trials and approved for different indications have been repurposed for bipolar disorder. We carried out a systematic meta-review of meta-analyses of randomized placebo-controlled trials investigating repurposed drugs as adjunctive treatments for mania and bipolar depression. We performed a critical appraisal using 'A MeaSurement Tool to Assess systematic Reviews' Version 2 (AMSTAR 2). We synthesized results on efficacy, tolerability, and safety, assessing evidence quality according to the 'Grading of Recommendations, Assessment, Development and Evaluations' (GRADE) approach. Our systematic search identified nine eligible studies investigating 12 drugs, four for mania and eight for bipolar depression. The quality of reporting was heterogeneous according to AMSTAR 2. In mania, allopurinol (for symptoms reduction and remission at 4-8 weeks) and tamoxifen (for response and symptoms reduction at 4-6 weeks) showed higher efficacy than placebo, with low and very low quality of evidence, respectively. Concerning bipolar depression, modafinil/armodafinil (for response, remission, and symptoms reduction at 6-8 weeks) and pramipexole (for response and symptoms reduction at 6 weeks) were superior to placebo, despite the low quality of evidence. Results on the efficacy of celecoxib and N-acetylcysteine were of low quality and limited to certain outcomes. Overall, the lack of evidence of high and moderate quality does not allow us to draw firm conclusions on the clinical utility of repurposed drugs as adjunctive treatments for mania and bipolar depression, highlighting the need for additional research.

Efficacy of Cannabidiol for Δ-9-Tetrahydrocannabinol-Induced Psychotic Symptoms, Schizophrenia, and Cannabis Use Disorders: A Narrative Review.

Although cannabis' major psychoactive component, Δ-9-tetrahydrocannabinol (THC), has been linked to both earlier onset and poorer outcomes of psychotic disorders, Cannabidiol (CBD) seems to have different pharmacological mechanisms and potential therapeutic properties. However, no clinical study has investigated CBD for the treatment of co-occurring psychotic and cannabis use disorders so far, even though its utility seems grounded in a plausible biological basis. The aim of this work is thus to provide an overview of available clinical studies evaluating the efficacy of CBD for psychotic symptoms induced by THC, schizophrenia, and cannabis use disorders. After searching for relevant studies in PubMed, Cochrane Library, and ClinicalTrials.gov, we included 10 clinical studies. Available evidence suggests that CBD may attenuate both psychotic-like symptoms induced by THC in healthy volunteers and positive symptoms in individuals with schizophrenia. In addition, preliminary data on the efficacy of CBD for cannabis use disorders show mixed findings. Evidence from ongoing clinical studies will provide insight into the possible role of CBD for treating psychotic and cannabis use disorders.