Best practice for integrating digital interventions into clinical care for young people at risk of suicide: a Delphi study.

BACKGROUND: Digital tools have the capacity to complement and enhance clinical care for young people at risk of suicide. Despite the rapid rise of digital tools, their rate of integration into clinical practice remains low. The poor uptake of digital tools may be in part due to the lack of best-practice guidelines for clinicians and services to safely apply them with this population. METHODS: A Delphi study was conducted to produce a set of best-practice guidelines for clinicians and services on integrating digital tools into clinical care for young people at risk of suicide. First, a questionnaire was developed incorporating action items derived from peer-reviewed and grey literature, and stakeholder interviews with 17 participants. Next, two independent expert panels comprising professionals (academics and clinical staff; n = 20) and young people with lived experience of using digital technology for support with suicidal thoughts and behaviours (n = 29) rated items across two consensus rounds. Items reaching consensus (rated as "essential" or "important" by at least 80% of panel members) at the end of round two were collated into a set of guidelines. RESULTS: Out of 326 individual items rated by the panels, 188 (57.7%) reached consensus for inclusion in the guidelines. The endorsed items provide guidance on important topics when working with young people, including when and for whom digital tools should be used, how to select a digital tool and identify potentially harmful content, and identifying and managing suicide risk conveyed via digital tools. Several items directed at services (rather than individual clinicians) were also endorsed. CONCLUSIONS: This study offers world-first evidence-informed guidelines for clinicians and services to integrate digital tools into clinical care for young people at risk of suicide. Implementation of the guidelines is an important next step and will hopefully lead to improved uptake of potentially helpful digital tools in clinical practice.

Proximity of alcohol outlets and presentation to hospital by young people after self-harm: A retrospective geospatial study using the integrated data infrastructure.

OBJECTIVES: There is a well-established association between alcohol use, misuse, intoxication and self-harm, the latter of which is associated with suicide. This study aimed to better understand the association between proximity to alcohol outlets and the likelihood of young people presenting to hospital following self-harm. METHODS: This was a nationwide retrospective geospatial study using data from the New Zealand Integrated Data Infrastructure using population-level data for 10-29-year-olds for the 2018 and 2017 calendar years. Presentations to hospital following self-harm were identified using the national minimum data set. Proximity to alcohol outlets was defined in road network distance (in kilometres) and ascertained using Integrated Data Infrastructure geospatial data. Alternative measures of proximity were employed in sensitivity analyses. Complete-case two-level random intercept logistic regression models were used to estimate the relationship between alcohol outlet proximity and hospital presentation for self-harm. Adjusted models included sex, age, ethnicity, area-level deprivation, urbanicity and distance to nearest medical facility. Analyses were also stratified by urbanicity. RESULTS: Of the 1,285,368 individuals (mean [standard deviation] age 20.0 [5.9] years), 7944 (0.6%) were admitted to hospital for self-harm. Overall, the odds of presenting to hospital for self-harm significantly decreased as the distance from the nearest alcohol outlet increased, including in adjusted models (adjusted odds ratio 0.980; 95% confidence interval = [0.969-0.992]); the association was robust to changes in the measure of alcohol proximity. The effect direction was consistent across all categorisations of urbanicity, but only statistically significant in large urban areas and rural areas. CONCLUSIONS: The findings of this study show a clear association between young people's access to alcohol outlets and presentation to hospital for self-harm and may provide a mandate for government policies and universal interventions to reduce young people's access to alcohol outlets. Further research regarding causative mechanisms is needed.

Prevalence and Correlates of Tobacco Use in Young People Presenting to Australian Primary Mental Health Services.

INTRODUCTION: In Australian youth primary mental health settings it is unclear as to the rates and correlates of tobacco use at service entry. AIMS AND METHODS: We aimed to delineate the prevalence and correlates of recent tobacco use (eg, cigarettes, chewing tobacco, cigars, etc) in the past 3 months in young people at their first presentation to primary mental health services as a function of age. Cross-sectional self-report measures were collected using a tablet device from young people presenting to one of five Australian primary mental health (headspace) services. Logistic regression assessed correlates of past 3-month tobacco use in adolescents (12-17 years) and young adults (18-25 years). RESULTS: Regular (at least monthly) tobacco use in the past 3 months was found in 23.4% (n = 247, N = 1055) of the sample. Increasing age (odds ratio [OR] =1.47 per year; 95% confidence interval [CI]: 1.15 to 1.89), male sex (OR = 1.98; 95% CI: 1.02 to 3.83), being in a relationship (OR = 1.96; 95% CI: 1.01 to 3.82), and poorer functioning (OR = 0.95 per unit Social and Occupational Functioning Assessment Scale increase; 95% CI: 0.91 to 0.99) predicted regular tobacco use in adolescents, but not in young adults. Living in a regional location (OR = 2.10; 95% CI: 1.40 to 3.13) and not studying (OR = 0.47; 95% CI: 0.31 to 0.73) predicted tobacco use in young adults. Having a diagnosed mental illness other than depression and/or anxiety predicted tobacco use in both groups (adolescents OR = 2.49; 95% CI: 1.26 to 4.94; young adults OR = 1.80; 95% CI: 1.13 to 2.89). CONCLUSIONS: Nearly a quarter of young people with mental illness are using tobacco, supporting the need for early intervention approaches. Adapting treatment targets by age could improve the impact of interventions in adolescents versus young adults. Poor functioning and lack of engagement in education were associated with tobacco use in both age groups, respectively; however, more research is needed to determine the direction of these relationships. IMPLICATIONS: Young people with mental illness have a high prevalence of recent tobacco use and this is evident when they first present to youth primary mental health services. Youth-oriented mental health settings may provide a unique window for tobacco use prevention and early intervention to reduce smoking in people with mental illness, a priority population. Age-specific targeted approaches might be needed in adolescents and young adults.

Predictors of suicidal ideation severity among treatment-seeking young people with major depressive disorder: The role of state and trait anxiety.

OBJECTIVE: Depression and suicidal ideation are closely intertwined. Yet, among young people with depression, the specific factors that contribute to changes in suicidal ideation over time are uncertain. Factors other than depressive symptom severity, such as comorbid psychopathology and personality traits, might be important contributors. Our aim was to identify contributors to fluctuations in suicidal ideation severity over a 12-week period in young people with major depressive disorder receiving cognitive behavioural therapy. METHODS: Data were drawn from two 12-week randomised, placebo-controlled treatment trials. Participants (N = 283) were 15-25 years old, with moderate to severe major depressive disorder. The primary outcome measure was the Suicidal Ideation Questionnaire, administered at baseline and weeks 4, 8 and 12. A series of linear mixed models was conducted to examine the relationship between Suicidal Ideation Questionnaire score and demographic characteristics, comorbid psychopathology, personality traits and alcohol use. RESULTS: Depression and anxiety symptom severity, and trait anxiety, independently predicted higher suicidal ideation, after adjusting for the effects of time, demographics, affective instability, non-suicidal self-injury and alcohol use. CONCLUSIONS: Both state and trait anxiety are important longitudinal correlates of suicidal ideation in depressed young people receiving cognitive behavioural therapy, independent of depression severity. Reducing acute psychological distress, through reducing depression and anxiety symptom severity, is important, but interventions aimed at treating trait anxiety could also potentially be an effective intervention approach for suicidal ideation in young people with depression.

Understanding the complexity, patterns, and correlates of alcohol and other substance use among young people seeking help for mental ill-health.

PURPOSE: Use of alcohol and other substances is a multifaceted issue impacting young people across multiple life domains. This paper aims to elucidate patterns of substance use and associated demographic and clinical factors among young people seeking treatment for their mental health. METHODS: Young people (12-25 years old) were recruited from five youth-specific primary mental health ("headspace") services in Australia. Self-reported substance use and harms in the past 3 months were measured using WHO-ASSIST. Network analyses were conducted to evaluate interrelationships between use and harms associated with different substances. Subgroups were then identified based on whether participants reported using high centrality substances, and associated demographic and clinical factors were assessed with multinomial logistic regression. RESULTS: 1107 youth participated. 70% reported use of at least one substance in the past 3 months, with around 30% of those reporting related health, social, legal or financial problems. Network analysis highlighted substantial interconnections between use and harm indicators for all substances, with amphetamine-type stimulants (ATS) and cannabis being high central substances. Higher levels of substance use and harms were reported in subgroups with ATS or cannabis use and different risk factors were associated with these subgroups. CONCLUSIONS: Findings highlight the importance of screening for substance use in youth primary mental healthcare settings, offering a key opportunity for early intervention. Clinicians should be aware of the inner connections of use and harms of different drugs and the role of cannabis and amphetamine use as a marker for more substance use profiles.

Applying the Theoretical Domains Framework to Develop an Intervention to 'Re-implement' Parent-Child Interaction Therapy (PCIT).

Parent-Child Interaction Therapy (PCIT) is an empirically supported treatment for childhood conduct problems, with increasing numbers of clinicians being trained in Aotearoa/New Zealand. However, ensuring sustained delivery of effective treatments by trained clinicians in routine care environments is notoriously challenging. The aims of this qualitative study were to (1) systematically examine and prioritise PCIT implementation barriers and facilitators, and (2) develop a well specified and theory-driven 're-implementation' intervention to support already-trained clinicians to resume or increase their implementation of PCIT. To triangulate and refine existing understanding of PCIT implementation determinants from an earlier cross-sectional survey, we integrated previously unanalysed qualitative survey data (54 respondents; response rate 60%) with qualitative data from six new focus groups with 15 PCIT-trained clinicians and managers in Aotearoa/New Zealand. We deductively coded data, using a directed content analysis process and the Theoretical Domains Framework, resulting in the identification of salient theoretical domains and belief statements within these. We then used the Theory and Techniques Tool to identify behaviour change techniques, possible intervention components, and their hypothesised mechanisms of action. Eight of the 14 theoretical domains were identified as influential on PCIT-trained clinician implementation behaviour (Knowledge; Social/Professional Role and Identity; Beliefs about Capabilities; Beliefs about Consequences; Memory, Attention and Decision Processes; Environmental Context and Resources; Social Influences; Emotion). Two of these appeared to be particularly salient: (1) 'Environmental Context and Resources', specifically lacking suitable PCIT equipment, with (lack of) access to a well-equipped clinic room appearing to influence implementation behaviour in several ways. (2) 'Social/Professional Role and Identity', with beliefs relating to a perception that colleagues view time-out as harmful to children, concerns that internationally-developed PCIT is not suitable for non-Maori clinicians to deliver to Indigenous Maori families, and clinicians feeling obligated yet isolated in their advocacy for PCIT delivery. In conclusion, where initial implementation has stalled or languished, re-implementation may be possible, and makes good sense, both fiscally and practically. This study suggests that re-implementation of PCIT in Aotearoa/New Zealand may be facilitated by intervention components such as ensuring access to a colleague or co-worker who is supportive of PCIT delivery, access to suitable equipment (particularly a time-out room), and targeted additional training for clinicians relating to the safety of time-out for children. The feasibility and acceptability of these intervention components will be tested in a future clinical trial.

Development of guidelines for school staff on supporting students who self-harm: a Delphi study.

OBJECTIVE: Self-harm is a major public health issue that significantly impacts communities, making early intervention and prevention paramount in addressing this public health issue. This study aimed to develop evidence-based, culturally responsive, safe, and practical guidelines to assist school staff in effectively supporting students who self-harm. METHODS: This Delphi study comprised of a five-step process, oversighted by a Ropu Matanga Maori (Maori clinical and cultural governance group), and drawing on the expertise and knowledge gained from existing literature, interviews with stakeholders, and two panels of experts (youth and stakeholders). The Ropu Matanga Maori ensured accountability to the principles of Te Tiriti o Waitangi (Treaty of Waitangi) and kept Maori processes central to the research aims. The panels completed two rounds of questionnaires, rating their endorsement of each statement. Statements rated as important or essential by 80% or more of both panels and Maori participants were included in the final guidelines. The Ropu Matanga Maori reviewed any remaining statements to determine inclusion. RESULTS: Following the five-step process, 305 statements were included in the guidelines. These statements provided guiding actions that endorsed communication, collaborative responsibility, and wellbeing and a student-centred approach. CONCLUSION: The guidelines provide guidance to all school staff that is culturally responsive and safe, consensus-based, and evidence-based. It is informed by the voices and experiences of young people and those who support them.

Adapting a codesign process with young people to prioritize outcomes for a systematic review of interventions to prevent self-harm and suicide.

BACKGROUND: Research and clinical outcomes that matter to people with lived experience can significantly differ from those outcomes studied by researchers. To inform a future Cochrane review of suicide and self-harm prevention interventions, we aimed to work with young people with relevant lived experience to agree on priority outcomes. DESIGN: Four participatory codesign workshops were completed across two sites (New Zealand, United Kingdom) with 28 young people in total. We iteratively adapted the methods over the course of the study. RESULTS: 'Improved coping' and 'safer/more accepting environment to disclose' were the final top-rated outcomes. 'Reduction of self-harm' was considered a low priority as it could be misleading, stigmatizing and was considered a secondary consequence of other improvements. In contrast to typical research outcomes, young people emphasized the diversity of experience, the dynamic nature of improvement and holistic and asset-based framing. Methodologically, dialogue using design materials (personas) to thematically explore outcomes was effective in overcoming the initial challenge of disparate quantitative ratings. DISCUSSION: The results will directly inform the development of a Cochrane review, enabling identification of whether and how outcomes of most importance to young people are measured in trials. Rather than producing discrete measurable outcomes that could be easily added to the systematic review, the young people challenged the academic conceptualization of outcomes, with implications for future evidence synthesis and intervention research, and for future codesign. PATIENT OR PUBLIC CONTRIBUTION: Young people with lived experience were codesigners of the outcomes, and their feedback informed iterative changes to the study methods.

Suicide risk assessments: Why are we still relying on these a decade after the evidence showed they perform poorly?

Suicide deaths have a profound impact on whanau and community and are a tragic loss. However, from a statistical point of view, suicide is a relatively rare event. Predicting rare events is difficult, and the implications for suicide prevention were highlighted in an important editorial in this journal more than a decade ago, yet little seems to have changed. Risk assessment that focuses on accurate prediction of suicide in real-world contexts is given a great deal of attention in mental health services, despite the fact that current scientific knowledge and best practice guidelines in this area highlight that it is unlikely to be a good basis on which to provide access to treatment. It is our view that we have a good enough understanding of the common conditions people who struggle with suicidal distress experience and energy is better directed at acting to reduce exposure to these conditions and providing treatment for those who seek it. Blueprints for successful suicide prevention exist. If we lessen the focus on prediction, we will have greater resources to focus on treatment and prevention.

A Chatbot to Support Young People During the COVID-19 Pandemic in New Zealand: Evaluation of the Real-World Rollout of an Open Trial.

BACKGROUND: The number of young people in New Zealand (Aotearoa) who experience mental health challenges is increasing. As those in Aotearoa went into the initial COVID-19 lockdown, an ongoing digital mental health project was adapted and underwent rapid content authoring to create the Aroha chatbot. This dynamic digital support was designed with and for young people to help manage pandemic-related worry. OBJECTIVE: Aroha was developed to provide practical evidence-based tools for anxiety management using cognitive behavioral therapy and positive psychology. The chatbot included practical ideas to maintain social and cultural connection, and to stay active and well. METHODS: Stay-at-home orders under Aotearoa's lockdown commenced on March 20, 2020. By leveraging previously developed chatbot technology and broader existing online trial infrastructure, the Aroha chatbot was launched promptly on April 7, 2020. Dissemination of the chatbot for an open trial was via a URL, and feedback on the experience of the lockdown and the experience of Aroha was gathered via online questionnaires and a focus group, and from community members. RESULTS: In the 2 weeks following the launch of the chatbot, there were 393 registrations, and 238 users logged into the chatbot, of whom 127 were in the target age range (13-24 years). Feedback guided iterative and responsive content authoring to suit the dynamic situation and motivated engineering to dynamically detect and react to a range of conversational intents. CONCLUSIONS: The experience of the implementation of the Aroha chatbot highlights the feasibility of providing timely event-specific digital mental health support and the technology requirements for a flexible and enabling chatbot architectural framework.

Young people and adult stakeholders' reflections on how school staff should support students who self-harm: A qualitative study.

INTRODUCTION: Self-harm is a significant public health issue affecting school communities, students, and families. The school is an ideal environment for early intervention and prevention. This study aimed to explore the views of young people and stakeholders on how school staff should support students who self-harm in the context of developing accessible and acceptable guidelines. METHODS: The study was nested within a larger Delphi study conducted in New Zealand. Two panels were asked to provide reflection in open text boxes in two questionnaires on how school staff can support students who self-harm. The youth panel included 22 participants between 16 and 25 years, and 81.8% identified as female and 18.3% as male. The stakeholder panel (e.g., school staff) included 27 participants over 25 years, and 63.0% identified as female, and 37.0% as male. The data were analyzed using thematic analysis to identify key themes. RESULTS: Eight themes were identified; (1) an approach that prioritizes trust, (2) an approach that recognizes students' agency, (3) an individually tailored approach, (4) a whole-school approach, (5) an approach that recognizes role boundaries, (6) an approach that prioritizes safety, (7) a nonpunitive approach, and (8) an appropriately-resourced approach. CONCLUSION: The eight themes identified highlighted ineffective practices in response to self-harm in schools. The eight themes provide solutions to these practices. Our findings highlighted four recommendations that address ineffective management approaches in response to students who self-harm. These recommendations included using a student-centered approach, a whole-school approach, avoiding punitive approaches, and providing adequate resourcing to schools.

The Neuropsychological Symptoms Self-Report: psychometric properties in an adolescent and young adult mental health cohort.

BACKGROUND: Subjective cognitive symptoms are common in young people receiving mental health treatment and are associated with poorer outcomes. The aim of this study was to determine the psychometric properties of the Neuropsychological Symptoms Self-Report (NSSR), an eight-item measure recently developed to provide a snapshot of young people's perceived change in cognitive functioning in relation to mental health treatment. METHOD: The sample included 633 youth aged 12-25 years (Mage = 18.2, 66.5% female, 88.6% Australian-born) who had sought mental health treatment in primary headspace services. At three-month follow-up, participants completed the NSSR and self-report measures of depression and anxiety. RESULTS: Excellent internal consistency was found: Cronbach's alpha = 0.93. The NSSR had negative correlations with self-reported anxiety (r = -.33, p < .001) and depression (r = -.48, p < .001) symptoms, suggesting a link with affective symptoms, but still independence of constructs. Exploratory and confirmatory factor analyses supported a single-factor model. Item response theory (IRT) analysis suggested good model fit (homogeneity, data integrity, scalability, local independence and monotonicity) for all items. There was some evidence of measurement noninvariance (for item thresholds) by sex and age, but not diagnosis. IRT models also supported briefer six- and three-item versions of the NSSR. CONCLUSION: In busy clinical practice, clinicians need a rapid and reliable method for determining whether cognitive symptoms are of concern and in need of further assessment and treatment. Study findings support the NSSR as a brief, psychometrically sound measure for assessing subjective cognitive functioning in adolescents and young adults receiving mental health treatment.

Assessing Suicidal Ideation in Young People With Depression: Factor Structure of the Suicidal Ideation Questionnaire.

Evaluating suicidal ideation in young people seeking mental health treatment is an important component of clinical assessment and treatment planning. To reduce the burden of youth suicide, we need to improve our understanding of suicidal ideation, its underlying constructs, and how ideation translates into suicidal behaviour. Using exploratory factor analysis, we investigated the dimensionality of the Suicidal Ideation Questionnaire (SIQ) among 273 participants aged 15-25 with Major Depressive Disorder. Area under the receiver operating characteristic curve (AUROC) analysis was used to explore associations between latent factors and actual suicidal behaviour. Findings suggested that the SIQ assesses multiple factors underlying suicidal ideation. AUROC analyses demonstrated that latent factors relating to both active and passive suicidal ideation predicted past-month suicidal behaviour and suicide attempt. These findings contribute to an improved understanding of the complexities of suicidal ideation and relationships with suicidal behaviour in young people with depression.

Pharmacological interventions for self-harm in adults.

BACKGROUND: Self-harm (SH; intentional self-poisoning or self-injury regardless of degree of suicidal intent or other types of motivation) is a growing problem in most countries, often repeated, and associated with suicide. Evidence assessing the effectiveness of pharmacological agents and/or natural products in the treatment of SH is lacking, especially when compared with the evidence for psychosocial interventions. This review therefore updates a previous Cochrane Review (last published in 2015) on the role of pharmacological interventions for SH in adults. OBJECTIVES: To assess the effects of pharmacological agents or natural products for SH compared to comparison types of treatment (e.g. placebo or alternative pharmacological treatment) for adults (aged 18 years or older) who engage in SH. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Specialised Register, the Cochrane Library (Central Register of Controlled Trials [CENTRAL] and Cochrane Database of Systematic Reviews [CDSR]), together with MEDLINE. Ovid Embase and PsycINFO (to 4 July 2020). SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing pharmacological agents or natural products with placebo/alternative pharmacological treatment in individuals with a recent (within six months of trial entry) episode of SH resulting in presentation to hospital or clinical services. The primary outcome was the occurrence of a repeated episode of SH over a maximum follow-up period of two years. Secondary outcomes included treatment acceptability, treatment adherence, depression, hopelessness, general functioning, social functioning, suicidal ideation, and suicide. DATA COLLECTION AND ANALYSIS: We independently selected trials, extracted data, and appraised trial quality. For binary outcomes, we calculated odds ratios (ORs) and their 95% confidence internals (CIs). For continuous outcomes we calculated the mean difference (MD) or standardised mean difference (SMD) and 95% CI. The overall certainty of evidence for the primary outcome (i.e. repetition of SH at post-intervention) was appraised for each intervention using the GRADE approach. MAIN RESULTS: We included data from seven trials with a total of 574 participants. Participants in these trials were predominately female (63.5%) with a mean age of 35.3 years (standard deviation (SD) 3.1 years). It is uncertain if newer generation antidepressants reduce repetition of SH compared to placebo (OR 0.59, 95% CI 0.29 to 1.19; N = 129; k = 2; very low-certainty evidence). There may be a lower rate of SH repetition for antipsychotics (21%) as compared to placebo (75%) (OR 0.09, 95% CI 0.02 to 0.50; N = 30; k = 1; low-certainty evidence). However, there was no evidence of a difference between antipsychotics compared to another comparator drug/dose for repetition of SH (OR 1.51, 95% CI 0.50 to 4.58; N = 53; k = 1; low-certainty evidence). There was also no evidence of a difference for mood stabilisers compared to placebo for repetition of SH (OR 0.99, 95% CI 0.33 to 2.95; N = 167; k = 1; very low-certainty evidence), or for natural products compared to placebo for repetition of SH (OR 1.33, 95% CI 0.38 to 4.62; N = 49; k = 1; lo- certainty) evidence. AUTHORS' CONCLUSIONS: Given the low or very low quality of the available evidence, and the small number of trials identified, there is only uncertain evidence regarding pharmacological interventions in patients who engage in SH. More and larger trials of pharmacotherapy are required, preferably using newer agents. These might include evaluation of newer atypical antipsychotics. Further work should also include evaluation of adverse effects of pharmacological agents. Other research could include evaluation of combined pharmacotherapy and psychological treatment.

Psychosocial interventions for self-harm in adults.

BACKGROUND: Self-harm (SH; intentional self-poisoning or self-injury regardless of degree of suicidal intent or other types of motivation) is a growing problem in most counties, often repeated, and associated with suicide. There has been a substantial increase in both the number of trials and therapeutic approaches of psychosocial interventions for SH in adults. This review therefore updates a previous Cochrane Review (last published in 2016) on the role of psychosocial interventions in the treatment of SH in adults. OBJECTIVES: To assess the effects of psychosocial interventions for self-harm (SH) compared to comparison types of care (e.g. treatment-as-usual, routine psychiatric care, enhanced usual care, active comparator) for adults (aged 18 years or older) who engage in SH. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Specialised Register, the Cochrane Library (Central Register of Controlled Trials [CENTRAL] and Cochrane Database of Systematic reviews [CDSR]), together with MEDLINE, Ovid Embase, and PsycINFO (to 4 July 2020). SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing interventions of specific psychosocial treatments versus treatment-as-usual (TAU), routine psychiatric care, enhanced usual care (EUC), active comparator, or a combination of these, in the treatment of adults with a recent (within six months of trial entry) episode of SH resulting in presentation to hospital or clinical services. The primary outcome was the occurrence of a repeated episode of SH over a maximum follow-up period of two years. Secondary outcomes included treatment adherence, depression, hopelessness, general functioning, social functioning, suicidal ideation, and suicide. DATA COLLECTION AND ANALYSIS: We independently selected trials, extracted data, and appraised trial quality. For binary outcomes, we calculated odds ratio (ORs) and their 95% confidence intervals (CIs). For continuous outcomes, we calculated mean differences (MDs) or standardised mean differences (SMDs) and 95% CIs. The overall quality of evidence for the primary outcome (i.e. repetition of SH at post-intervention) was appraised for each intervention using the GRADE approach. MAIN RESULTS: We included data from 76 trials with a total of 21,414 participants. Participants in these trials were predominately female (61.9%) with a mean age of 31.8 years (standard deviation [SD] 11.7 years). On the basis of data from four trials, individual cognitive behavioural therapy (CBT)-based psychotherapy may reduce repetition of SH as compared to TAU or another comparator by the end of the intervention (OR 0.35, 95% CI 0.12 to 1.02; N = 238; k = 4; GRADE: low certainty evidence), although there was imprecision in the effect estimate. At longer follow-up time points (e.g., 6- and 12-months) there was some evidence that individual CBT-based psychotherapy may reduce SH repetition. Whilst there may be a slightly lower rate of SH repetition for dialectical behaviour therapy (DBT) (66.0%) as compared to TAU or alternative psychotherapy (68.2%), the evidence remains uncertain as to whether DBT reduces absolute repetition of SH by the post-intervention assessment. On the basis of data from a single trial, mentalisation-based therapy (MBT) reduces repetition of SH and frequency of SH by the post-intervention assessment (OR 0.35, 95% CI 0.17 to 0.73; N = 134; k = 1; GRADE: high-certainty evidence). A group-based emotion-regulation psychotherapy may also reduce repetition of SH by the post-intervention assessment based on evidence from two trials by the same author group (OR 0.34, 95% CI 0.13 to 0.88; N = 83; k = 2; moderate-certainty evidence). There is probably little to no effect for different variants of DBT on absolute repetition of SH, including DBT group-based skills training, DBT individual skills training, or an experimental form of DBT in which participants were given significantly longer cognitive exposure to stressful events. The evidence remains uncertain as to whether provision of information and support, based on the Suicide Trends in At-Risk Territories (START) and the SUicide-PREvention Multisite Intervention Study on Suicidal behaviors (SUPRE-MISS) models, have any effect on repetition of SH by the post-intervention assessment. There was no evidence of a difference for psychodynamic psychotherapy, case management, general practitioner (GP) management, remote contact interventions, and other multimodal interventions, or a variety of brief emergency department-based interventions. AUTHORS' CONCLUSIONS: Overall, there were significant methodological limitations across the trials included in this review. Given the moderate or very low quality of the available evidence, there is only uncertain evidence regarding a number of psychosocial interventions for adults who engage in SH. Psychosocial therapy based on CBT approaches may result in fewer individuals repeating SH at longer follow-up time points, although no such effect was found at the post-intervention assessment and the quality of evidence, according to the GRADE criteria, was low. Given findings in single trials, or trials by the same author group, both MBT and group-based emotion regulation therapy should be further developed and evaluated in adults. DBT may also lead to a reduction in frequency of SH. Other interventions were mostly evaluated in single trials of moderate to very low quality such that the evidence relating to the use of these interventions is inconclusive at present.

Interventions for self-harm in children and adolescents.

BACKGROUND: Self-harm (SH; intentional self-poisoning or self-injury regardless of degree of suicidal intent or other types of motivation) is a growing problem in most countries, often repeated, and associated with suicide. Evidence assessing the effectiveness of interventions in the treatment of SH in children and adolescents is lacking, especially when compared with the evidence for psychosocial interventions in adults. This review therefore updates a previous Cochrane Review (last published in 2015) on the role of interventions for SH in children and adolescents. OBJECTIVES: To assess the effects of psychosocial interventions or pharmacological agents or natural products for SH compared to comparison types of care (e.g. treatment-as-usual, routine psychiatric care, enhanced usual care, active comparator, placebo, alternative pharmacological treatment, or a combination of these) for children and adolescents (up to 18 years of age) who engage in SH. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Specialized Register, the Cochrane Library (Central Register of Controlled Trials [CENTRAL] and Cochrane Database of Systematic Reviews [CDSR]), together with MEDLINE, Ovid Embase, and PsycINFO (to 4 July 2020). SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing specific psychosocial interventions or pharmacological agents or natural products with treatment-as-usual (TAU), routine psychiatric care, enhanced usual care (EUC), active comparator, placebo, alternative pharmacological treatment, or a combination of these, in children and adolescents with a recent (within six months of trial entry) episode of SH resulting in presentation to hospital or clinical services. The primary outcome was the occurrence of a repeated episode of SH over a maximum follow-up period of two years. Secondary outcomes included treatment adherence, depression, hopelessness, general functioning, social functioning, suicidal ideation, and suicide. DATA COLLECTION AND ANALYSIS: We independently selected trials, extracted data, and appraised trial quality. For binary outcomes, we calculated odds ratios (ORs) and their 95% confidence internals (CIs). For continuous outcomes, we calculated the mean difference (MD) or standardised mean difference (SMD) and 95% CIs. The overall quality of evidence for the primary outcome (i.e. repetition of SH at post-intervention) was appraised for each intervention using the GRADE approach. MAIN RESULTS: We included data from 17 trials with a total of 2280 participants. Participants in these trials were predominately female (87.6%) with a mean age of 14.7 years (standard deviation (SD) 1.5 years). The trials included in this review investigated the effectiveness of various forms of psychosocial interventions. None of the included trials evaluated the effectiveness of pharmacological agents in this clinical population. There was a lower rate of SH repetition for DBT-A (30%) as compared to TAU, EUC, or alternative psychotherapy (43%) on repetition of SH at post-intervention in four trials (OR 0.46, 95% CI 0.26 to 0.82; N = 270; k = 4; high-certainty evidence). There may be no evidence of a difference for individual cognitive behavioural therapy (CBT)-based psychotherapy and TAU for repetition of SH at post-intervention (OR 0.93, 95% CI 0.12 to 7.24; N = 51; k = 2; low-certainty evidence). We are uncertain whether mentalisation based therapy for adolescents (MBT-A) reduces repetition of SH at post-intervention as compared to TAU (OR 0.70, 95% CI 0.06 to 8.46; N = 85; k = 2; very low-certainty evidence). Heterogeneity for this outcome was substantial ( I² = 68%). There is probably no evidence of a difference between family therapy and either TAU or EUC on repetition of SH at post-intervention (OR 1.00, 95% CI 0.49 to 2.07; N = 191; k = 2; moderate-certainty evidence). However, there was no evidence of a difference for compliance enhancement approaches on repetition of SH by the six-month follow-up assessment, for group-based psychotherapy at the six- or 12-month follow-up assessments, for a remote contact intervention (emergency cards) at the 12-month assessment, or for therapeutic assessment at the 12- or 24-month follow-up assessments. AUTHORS' CONCLUSIONS: Given the moderate or very low quality of the available evidence, and the small number of trials identified, there is only uncertain evidence regarding a number of psychosocial interventions in children and adolescents who engage in SH. Further evaluation of DBT-A is warranted. Given the evidence for its benefit in adults who engage in SH, individual CBT-based psychotherapy should also be further developed and evaluated in children and adolescents.

New generation antidepressants for depression in children and adolescents: a network meta-analysis.

BACKGROUND: Major depressive disorders have a significant impact on children and adolescents, including on educational and vocational outcomes, interpersonal relationships, and physical and mental health and well-being. There is an association between major depressive disorder and suicidal ideation, suicide attempts, and suicide. Antidepressant medication is used in moderate to severe depression; there is now a range of newer generations of these medications. OBJECTIVES: To investigate, via network meta-analysis (NMA), the comparative effectiveness and safety of different newer generation antidepressants in children and adolescents with a diagnosed major depressive disorder (MDD) in terms of depression, functioning, suicide-related outcomes and other adverse outcomes. The impact of age, treatment duration, baseline severity, and pharmaceutical industry funding was investigated on clinician-rated depression (CDRS-R) and suicide-related outcomes. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Specialised Register, the Cochrane Library (Central Register of Controlled Trials (CENTRAL) and Cochrane Database of Systematic Reviews (CDSR)), together with Ovid Embase, MEDLINE and PsycINFO till March 2020. SELECTION CRITERIA: Randomised trials of six to 18 year olds of either sex and any ethnicity with clinically diagnosed major depressive disorder were included. Trials that compared the effectiveness of newer generation antidepressants with each other or with a placebo were included. Newer generation antidepressants included: selective serotonin reuptake inhibitors; selective norepinephrine reuptake inhibitors (SNRIs); norepinephrine reuptake inhibitors; norepinephrine dopamine reuptake inhibitors; norepinephrine dopamine disinhibitors (NDDIs); and tetracyclic antidepressants (TeCAs). DATA COLLECTION AND ANALYSIS: Two reviewers independently screened titles/abstracts and full texts, extracted data, and assessed risk of bias. We analysed dichotomous data as Odds Ratios (ORs), and continuous data as Mean Difference (MD) for the following outcomes: depression symptom severity (clinician rated), response or remission of depression symptoms, depression symptom severity (self-rated), functioning, suicide related outcomes and overall adverse outcomes. Random-effects network meta-analyses were conducted in a frequentist framework using multivariate meta-analysis. Certainty of evidence was assessed using Confidence in Network Meta-analysis (CINeMA). We used "informative statements" to standardise the interpretation and description of the results. MAIN RESULTS: Twenty-six studies were included. There were no data for the two primary outcomes (depressive disorder established via clinical diagnostic interview and suicide), therefore, the results comprise only secondary outcomes. Most antidepressants may be associated with a "small and unimportant" reduction in depression symptoms on the CDRS-R scale (range 17 to 113) compared with placebo (high certainty evidence: paroxetine: MD -1.43, 95% CI -3.90, 1.04; vilazodone: MD -0.84, 95% CI -3.03, 1.35; desvenlafaxine MD -0.07, 95% CI -3.51, 3.36; moderate certainty evidence: sertraline: MD -3.51, 95% CI -6.99, -0.04; fluoxetine: MD -2.84, 95% CI -4.12, -1.56; escitalopram: MD -2.62, 95% CI -5.29, 0.04; low certainty evidence: duloxetine: MD -2.70, 95% CI -5.03, -0.37; vortioxetine: MD 0.60, 95% CI -2.52, 3.72; very low certainty evidence for comparisons between other antidepressants and placebo). There were "small and unimportant" differences between most antidepressants in reduction of depression symptoms (high- or moderate-certainty evidence). Results were similar across other outcomes of benefit. In most studies risk of self-harm or suicide was an exclusion criterion for the study. Proportions of suicide-related outcomes were low for most included studies and 95% confidence intervals were wide for all comparisons. The evidence is very uncertain about the effects of mirtazapine (OR 0.50, 95% CI 0.03, 8.04), duloxetine (OR 1.15, 95% CI 0.72, 1.82), vilazodone (OR 1.01, 95% CI 0.68, 1.48), desvenlafaxine (OR 0.94, 95% CI 0.59, 1.52), citalopram (OR 1.72, 95% CI 0.76, 3.87) or vortioxetine (OR 1.58, 95% CI 0.29, 8.60) on suicide-related outcomes compared with placebo. There is low certainty evidence that escitalopram may "at least slightly" reduce odds of suicide-related outcomes compared with placebo (OR 0.89, 95% CI 0.43, 1.84). There is low certainty evidence that fluoxetine (OR 1.27, 95% CI 0.87, 1.86), paroxetine (OR 1.81, 95% CI 0.85, 3.86), sertraline (OR 3.03, 95% CI 0.60, 15.22), and venlafaxine (OR 13.84, 95% CI 1.79, 106.90) may "at least slightly" increase odds of suicide-related outcomes compared with placebo. There is moderate certainty evidence that venlafaxine probably results in an "at least slightly" increased odds of suicide-related outcomes compared with desvenlafaxine (OR 0.07, 95% CI 0.01, 0.56) and escitalopram (OR 0.06, 95% CI 0.01, 0.56). There was very low certainty evidence regarding other comparisons between antidepressants. AUTHORS' CONCLUSIONS: Overall, methodological shortcomings of the randomised trials make it difficult to interpret the findings with regard to the efficacy and safety of newer antidepressant medications. Findings suggest that most newer antidepressants may reduce depression symptoms in a small and unimportant way compared with placebo. Furthermore, there are likely to be small and unimportant differences in the reduction of depression symptoms between the majority of antidepressants. However, our findings reflect the average effects of the antidepressants, and given depression is a heterogeneous condition, some individuals may experience a greater response. Guideline developers and others making recommendations might therefore consider whether a recommendation for the use of newer generation antidepressants is warranted for some individuals in some circumstances. Our findings suggest sertraline, escitalopram, duloxetine, as well as fluoxetine (which is currently the only treatment recommended for first-line prescribing) could be considered as a first option. Children and adolescents considered at risk of suicide were frequently excluded from trials, so that we cannot be confident about the effects of these medications for these individuals. If an antidepressant is being considered for an individual, this should be done in consultation with the child/adolescent and their family/caregivers and it remains critical to ensure close monitoring of treatment effects and suicide-related outcomes (combined suicidal ideation and suicide attempt) in those treated with newer generation antidepressants, given findings that some of these medications may be associated with greater odds of these events. Consideration of psychotherapy, particularly cognitive behavioural therapy, as per guideline recommendations, remains important.

Trajectories of change in depression symptoms and suicidal ideation over the course of evidence-based treatment for depression: Secondary analysis of a randomised controlled trial of cognitive behavioural therapy plus fluoxetine in young people.

OBJECTIVES: Effective treatment of depression is a key target for suicide prevention strategies. However, only around one-third of young people with suicide risk respond to evidence-based treatments. Understanding the trajectory of suicidal ideation, as a marker of suicide risk, over the course of evidence-based treatment for depression might provide insight into more targeted and effective treatments. METHODS: This is a secondary analysis of data from the multicentre Youth Depression Alleviation-Combined Treatment trial. A total of 153 young people aged 15-25 years diagnosed with major depressive disorder were randomly assigned in this double-blind, placebo-controlled trial to either cognitive behavioural therapy plus fluoxetine or cognitive behavioural therapy plus placebo. Participants were assessed for depression and suicidal ideation at baseline and at weeks 4, 8 and 12. RESULTS: Using group-based trajectory modelling, we identified two distinct depression trajectories. The first (Improving; 54.9%; n = 83) comprised those who experienced a consistent decline in depression symptoms. The second (Persisting; 45.1%; n = 70) comprised those who, despite treatment, still had clinically significant levels of depression by the end of treatment. For suicidal ideation, we identified four distinct trajectories: Non-clinical (15.5%; n = 20), Low Improving (47.1%; n = 75), High Improving (24.8%; n = 38) and High Persisting (12.7%; n = 20). Treatment allocation was not significantly associated with trajectory membership for either depression or suicidal ideation. CONCLUSION: Understanding the course of depression and suicidal ideation during treatment has important implications for managing suicide risk. The findings suggest that there is an identifiable group of young people for whom enhanced psychological and/or pharmacological intervention might be required to ensure a better treatment response. Specific interventions for those with suicidal ideation may also be prudent from the outset. CLINICAL TRIAL REGISTRATION: The Youth Depression Alleviation-Combined Treatment trial was prospectively registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12612001281886).

Debate: Gold standard or go for gold? The pros and cons of waiting for gold standard evidence of effectiveness for adolescent depression and self-harm interventions versus acting with the precautionary principle in current political times.

There is increasing concern about the prevalence of depression and self-harm among children adolescents in many countries. Governments who commission and fund psychological interventions to address these difficulties want to know what is effective. The techniques available for synthesising gold standard evidence are increasingly sophisticated, but there are many criticisms of being completely reliant on this approach. A precautionary approach, where public policy decision-makers acknowledge that where the evidence is limited, the benefits of certain interventions are thought to outweigh the risks, including the risk of doing nothing. This later element may be particularly important in the domain of depression and self-harm, as both are associated with elevated risk of death by suicide.

Youth Depression Alleviation with Anti-inflammatory Agents (YoDA-A): a randomised clinical trial of rosuvastatin and aspirin.

BACKGROUND: Inflammation contributes to the pathophysiology of major depressive disorder (MDD), and anti-inflammatory strategies might therefore have therapeutic potential. This trial aimed to determine whether adjunctive aspirin or rosuvastatin, compared with placebo, reduced depressive symptoms in young people (15-25 years). METHODS: YoDA-A, Youth Depression Alleviation with Anti-inflammatory Agents, was a 12-week triple-blind, randomised, controlled trial. Participants were young people (aged 15-25 years) with moderate to severe MDD (MADRS mean at baseline 32.5 ± 6.0; N = 130; age 20.2 ± 2.6; 60% female), recruited between June 2013 and June 2017 across six sites in Victoria, Australia. In addition to treatment as usual, participants were randomised to receive aspirin (n = 40), rosuvastatin (n = 48), or placebo (n = 42), with assessments at baseline and weeks 4, 8, 12, and 26. The primary outcome was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to week 12. RESULTS: At the a priori primary endpoint of MADRS differential change from baseline at week 12, there was no significant difference between aspirin and placebo (1.9, 95% CI (- 2.8, 6.6), p = 0.433), or rosuvastatin and placebo (- 4.2, 95% CI (- 9.1, 0.6), p = 0.089). For rosuvastatin, secondary outcomes on self-rated depression and global impression, quality of life, functioning, and mania were not significantly different from placebo. Aspirin was inferior to placebo on the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) at week 12. Statins were superior to aspirin on the MADRS, the Clinical Global Impressions Severity Scale (CGI-S), and the Negative Problem Orientation Questionnaire scale (NPOQ) at week 12. CONCLUSIONS: The addition of either aspirin or rosuvastatin did not to confer any beneficial effect over and above routine treatment for depression in young people. Exploratory comparisons of secondary outcomes provide limited support for a potential therapeutic role for adjunctive rosuvastatin, but not for aspirin, in youth depression. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12613000112763. Registered on 30/01/2013.