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.

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.

Polyunsaturated fatty acids metabolism, purine metabolism and inosine as potential independent diagnostic biomarkers for major depressive disorder in children and adolescents.

Major depressive disorder (MDD) in children and adolescents is a recurrent and disabling condition globally but its pathophysiology remains poorly elucidated and there are limited effective treatments available. We performed metabolic profiling of plasma samples based on ultra-high-performance liquid chromatography equipped with quadrupole time-offlight mass spectrometry to explore the potential biomarkers of depression in children and adolescents with MDD. We identified several perturbed pathways, including fatty acid metabolism-particularly the polyunsaturated fatty acids metabolism, and purine metabolism-that were associated with MDD in these young patients. In addition, inosine was shown as a potential independent diagnostic biomarker for MDD, achieving an area under the ROC curve of 0.999 in discriminating drug-naive MDD patients and 0.866 in discriminating drug-treated MDD from healthy controls. Moreover, we found evidence for differences in the pathophysiology of MDD in children and adolescents to that of adult MDD, specifically with tryptophan metabolism. Through metabolomic analysis, we have identified links between a framework of metabolic perturbations and the pathophysiology and diagnostic biomarker of child and adolescent MDD.

Case identification of mental health and related problems in children and young people using the New Zealand Integrated Data Infrastructure.

BACKGROUND: In a novel endeavour we aimed to develop a clinically relevant case identification method for use in research about the mental health of children and young people in New Zealand using the Integrated Data Infrastructure (IDI). The IDI is a linked individual-level database containing New Zealand government and survey microdata. METHODS: We drew on diagnostic and pharmaceutical information contained within five secondary care service use and medication dispensing datasets to identify probable cases of mental health and related problems. A systematic classification and refinement of codes, including restrictions by age, was undertaken to assign cases into 13 different mental health problem categories. This process was carried out by a panel of eight specialists covering a diverse range of mental health disciplines (a clinical psychologist, four child and adolescent psychiatrists and three academic researchers in child and adolescent mental health). The case identification method was applied to the New Zealand youth estimated resident population for the 2014/15 fiscal year. RESULTS: Over 82,000 unique individuals aged 0-24 with at least one specified mental health or related problem were identified using the case identification method for the 2014/15 fiscal year. The most prevalent mental health problem subgroups were emotional problems (31,266 individuals), substance problems (16,314), and disruptive behaviours (13,758). Overall, the pharmaceutical collection was the largest source of case identification data (59,862). CONCLUSION: This study demonstrates the value of utilising IDI data for mental health research. Although the method is yet to be fully validated, it moves beyond incidence rates based on single data sources, and provides directions for future use, including further linkage of data to the IDI.

Family therapy approaches for anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is characterised by a failure to maintain a normal body weight due to a paucity of nutrition, an intense fear of gaining weight or behaviour that prevents the individual from gaining weight, or both. The long-term prognosis is often poor, with severe developmental, medical and psychosocial complications, high rates of relapse and mortality. 'Family therapy approaches' indicate a range of approaches, derived from different theories, that involve the family in treatment. We have included therapies developed on the basis of dominant family systems theories, approaches that are based on or broadly similar to the family-based therapy derived from the Maudsley model, approaches that incorporate a focus on cognitive restructuring, as well as approaches that involve the family without articulation of a theoretical approach.This is an update of a Cochrane Review first published in 2010. OBJECTIVES: To evaluate the efficacy of family therapy approaches compared with standard treatment and other treatments for AN. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR) and PsycINFO (OVID) (all years to April 2016). We ran additional searches directly on Cochrane Central Register for Controlled Trials (CENTRAL), MEDLINE, Ovid Embase, and PsycINFO (to 2008 and 2016 to 2018). We searched the World Health Organization (WHO) trials portal (ICTRP) and ClinicalTrials.gov, together with four theses databases (all years to 2018). We checked the reference lists of all included studies and relevant systematic reviews. We have included in the analyses only studies from searches conducted to April 2016. SELECTION CRITERIA: Randomised controlled trials (RCTs) of family therapy approaches compared to any other intervention or other types of family therapy approaches were eligible for inclusion. We included participants of any age or gender with a primary clinical diagnosis of anorexia nervosa. DATA COLLECTION AND ANALYSIS: Four review authors selected the studies, assessed quality and extracted data. We used a random-effects meta-analysis. We used the risk ratio (with a 95% confidence interval) to summarise dichotomous outcomes and both the standardised mean difference and the mean difference to summarise continuous measures. MAIN RESULTS: We included 25 trials in this version of the review (13 from the original 2010 review and 12 newly-included studies). Sixteen trials were of adolescents, eight trials of adults (seven of these in young adults aged up to 26 years) and one trial included three age groups: one adolescent, one young adult and one adult. Most investigated family-based therapy or variants. Reporting of trial conduct was generally inadequate, so that in a large number of studies we rated the risk of bias as unclear for many of the domains. Selective reporting bias was particularly problematic, with 68% of studies rated at high risk of bias in this area, followed by incomplete outcome data, with 44% of studies rated at high risk of bias in this area. For the main outcome measure of remission there was some low-quality evidence (from only two studies, 81 participants) suggesting that family therapy approaches might offer some advantage over treatment as usual on rates of remission, post intervention (risk ratio (RR) 3.50, 95% confidence interval (CI) 1.49 to 8.23; I2 = 0%). However, at follow-up, low-quality evidence from only one study suggested this effect was not maintained. There was very low-quality evidence from only one trial, which means it is difficult to determine whether family therapy approaches offer any advantage over educational interventions for remission (RR 9.00, 95% CI 0.53 to 153.79; 1 study, N = 30). Similarly, there was very low-quality evidence from only five trials for remission post-intervention, again meaning that it is difficult to determine whether there is any advantage of family therapy approaches over psychological interventions (RR 1.22, 95% CI 0.89 to 1.67; participants = 252; studies = 5; I2 = 37%) and at long-term follow-up (RR 1.08, 95% CI 0.91 to 1.28; participants = 200; studies = 4 with 1 of these contributing 3 pairwise comparisons for different age groups; I2 = 0%). There was no indication that the age group had any impact on the overall treatment effect; however, it should be noted that there were very few trials undertaken in adults, with the age range of adult studies included in this analysis from 20 to 27. There was some evidence of a small effect favouring family based therapy compared with other psychological interventions in terms of weight gain post-intervention (standardised mean difference (SMD) 0.32, 95% CI 0.01 to 0.63; participants = 210; studies = 4 with 1 of these contributing 3 pairwise comparisons for different age groups; I2 = 11%) . Overall, there was insufficient evidence to determine whether there were any differences between groups across all comparisons for most of the secondary outcomes (weight, eating disorder psychopathology, dropouts, relapse, or family functioning measures), either at post-intervention or at follow-up. AUTHORS' CONCLUSIONS: There is a limited amount of low-quality evidence to suggest that family therapy approaches may be effective compared to treatment as usual in the short term. This finding is based on two trials that included only a small number of participants, and both had issues about potential bias. There is insufficient evidence to determine whether there is an advantage of family therapy approaches in people of any age compared to educational interventions (one study, very low quality) or other psychological therapies (five studies, very low quality). Most studies contributing to this finding were undertaken in adolescents and youth. There are clear potential impacts on how family therapy approaches might be delivered to different age groups and further work is required to understand what the resulting effects on treatment efficacy might be. There is insufficient evidence to determine whether one type of family therapy approach is more effective than another. The field would benefit from further large, well-conducted trials.

Family therapy approaches for anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is characterised by a failure to maintain a normal body weight due to a paucity of nutrition, an intense fear of gaining weight or behaviour that prevents the individual from gaining weight, or both. The long-term prognosis is often poor, with severe developmental, medical and psychosocial complications, high rates of relapse and mortality. 'Family therapy approaches' indicate a range of approaches, derived from different theories, that involve the family in treatment. We have included therapies developed on the basis of dominant family systems theories, approaches that are based on or broadly similar to the family-based therapy derived from the Maudsley model, approaches that incorporate a focus on cognitive restructuring, as well as approaches that involve the family without articulation of a theoretical approach.This is an update of a Cochrane Review first published in 2010. OBJECTIVES: To evaluate the efficacy of family therapy approaches compared with standard treatment and other treatments for AN. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR) and PsycINFO (OVID) (all years to April 2016). We ran additional searches directly on Cochrane Central Register for Controlled Trials (CENTRAL), MEDLINE, Ovid Embase, and PsycINFO (to 2008 and 2016 to 2018). We searched the World Health Organization (WHO) trials portal (ICTRP) and ClinicalTrials.gov, together with four theses databases (all years to 2018). We checked the reference lists of all included studies and relevant systematic reviews. We have included in the analyses only studies from searches conducted to April 2016. SELECTION CRITERIA: Randomised controlled trials (RCTs) of family therapy approaches compared to any other intervention or other types of family therapy approaches were eligible for inclusion. We included participants of any age or gender with a primary clinical diagnosis of anorexia nervosa. DATA COLLECTION AND ANALYSIS: Four review authors selected the studies, assessed quality and extracted data. We used a random-effects meta-analysis. We used the risk ratio (with a 95% confidence interval) to summarise dichotomous outcomes and both the standardised mean difference and the mean difference to summarise continuous measures. MAIN RESULTS: We included 25 trials in this version of the review (13 from the original 2010 review and 12 newly-included studies). Sixteen trials were of adolescents, eight trials of adults (seven of these in young adults aged up to 26 years) and one trial included three age groups: one adolescent, one young adult and one adult. Most investigated family-based therapy or variants. Reporting of trial conduct was generally inadequate, so that in a large number of studies we rated the risk of bias as unclear for many of the domains. Selective reporting bias was particularly problematic, with 68% of studies rated at high risk of bias in this area, followed by incomplete outcome data, with 44% of studies rated at high risk of bias in this area. For the main outcome measure of remission there was some low-quality evidence (from only two studies, 81 participants) suggesting that family therapy approaches might offer some advantage over treatment as usual on rates of remission, post intervention (risk ratio (RR) 3.50, 95% confidence interval (CI) 1.49 to 8.23; I2 = 0%). However, at follow-up, low-quality evidence from only one study suggested this effect was not maintained. There was very low-quality evidence from only one trial, which means it is difficult to determine whether family therapy approaches offer any advantage over educational interventions for remission (RR 9.00, 95% CI 0.53 to 153.79; 1 study, N = 30). Similarly, there was very low-quality evidence from only five trials for remission post-intervention, again meaning that it is difficult to determine whether there is any advantage of family therapy approaches over psychological interventions (RR 1.22, 95% CI 0.89 to 1.67; participants = 252; studies = 5; I2 = 37%) and at long-term follow-up (RR 1.08, 95% CI 0.91 to 1.28; participants = 200; studies = 4 with 1 of these contributing 3 pairwise comparisons for different age groups; I2 = 0%). There was no indication that the age group had any impact on the overall treatment effect; however, it should be noted that there were very few trials undertaken in adults, with the age range of adult studies included in this analysis from 20 to 27. There was some evidence of a small effect favouring family based therapy compared with other psychological interventions in terms of weight gain post-intervention (standardised mean difference (SMD) 0.32, 95% CI 0.01 to 0.63; participants = 210; studies = 4 with 1 of these contributing 3 pairwise comparisons for different age groups; I2 = 11%) . Overall, there was insufficient evidence to determine whether there were any differences between groups across all comparisons for most of the secondary outcomes (weight, eating disorder psychopathology, dropouts, relapse, or family functioning measures), either at post-intervention or at follow-up. AUTHORS' CONCLUSIONS: There is a limited amount of low-quality evidence to suggest that family therapy approaches may be effective compared to treatment as usual in the short term. This finding is based on two trials that included only a small number of participants, and both had issues about potential bias. There is insufficient evidence to determine whether there is an advantage of family therapy approaches in people of any age compared to educational interventions (one study, very low quality) or psychological therapies (five studies, very low quality). Most studies contributing to this finding were undertaken in adolescents and youth. There are clear potential impacts on how family therapy approaches might be delivered to different age groups and further work is required to understand what the resulting effects on treatment efficacy might be. There is insufficient evidence to determine whether one type of family therapy approach is more effective than another. The field would benefit from further large, well-conducted trials.

Psychological therapies for anxiety and depression in children and adolescents with long-term physical conditions.

BACKGROUND: Long-term physical conditions affect 10% to 12% of children and adolescents worldwide. These individuals are at greater risk of developing psychological problems, particularly anxiety and depression, sometimes directly related to their illness or medical care (e.g. health-related anxiety). There is limited evidence regarding the effectiveness of psychological therapies for treating anxiety and depression in this population. Therapies designed for children and adolescents without medical issues may or may not be appropriate for use with those who have long-term physical conditions. OBJECTIVES: This review was undertaken to assess the effectiveness and acceptability of psychological therapies in comparison with controls (treatment-as-usual, waiting list, attention placebo, psychological placebo, or non-psychological treatment) for treating anxiety and depression in children and adolescents with long-term physical conditions. SEARCH METHODS: We searched Ovid MEDLINE (1950- ), Embase (1974- ), PsycINFO (1967- ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 27 September 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD-CTR) (all years to May 2016). In addition we searched the Web of Science (Core Collection) (12 October 2018) and conducted a cited reference search for reports of all included trials. We handsearched relevant conference proceedings, reference lists of included articles, and grey literature. SELECTION CRITERIA: Randomised controlled trials (RCTs), cluster-randomised trials and cross-over trials of psychological therapies for treating anxiety or depression in children with long-term physical conditions were included. DATA COLLECTION AND ANALYSIS: Abstracts and complete articles were independently reviewed by two authors. Discrepancies were addressed by a third author. Odds ratio (OR) was used for comparing dichotomous data and standardised mean differences (SMD) for comparing continuous data. Meta-analysis was undertaken when treatments, participants, and the underlying clinical question were similar. Otherwise, narrative analysis of data was undertaken. MAIN RESULTS: Twenty-eight RCTs and one cross-over trial with 1349 participants were included in the review. Most participants were recruited from community settings and hospital clinics in high-income countries. For the primary outcome of treatment efficacy, short-term depression (versus any control), there was low-quality evidence from 16 trials involving 1121 participants suggesting that psychological therapies may be more effective than control therapies (SMD -0.31, 95% CI -0.59 to -0.03; I2 = 79%). For the primary outcome of treatment efficacy, short-term anxiety (versus any control), there was inadequate evidence of moderate-quality from 13 studies involving 578 participants to determine whether psychological therapies were more effective than control conditions (SMD -0.26, CI -0.59 to 0.07, I2 = 72%). Planned sensitivity analyses could not be undertaken for risk of bias due to the small number of trials that rated high for each domain. Additional sensitivity analysis demonstrated that psychological interventions specifically designed to reduce anxiety or depression were more effective than psychological therapies designed to improve other symptoms or general coping. There was some suggestion from subgroup analyses that they type of intervention (Chi² = 14.75, df = 5 (P = 0.01), I² = 66.1%), the severity of depression (Chi² = 23.29, df = 4 (P = 0.0001), I² = 82.8%) and the type of long-term physical condition (Chi² = 10.55, df = 4 (P = 0.03), I² = 62.1%) may have an impact on the overall treatment effect.There was qualitative (reported), but not quantitative evidence confirming the acceptability of selected psychological therapies for anxiety and depression. There was low-quality evidence that psychological therapies were more effective than control conditions in improving quality of life (SMD 1.13, CI 0.44 to 1.82, I2 = 89%) and symptoms of long-term physical conditions (SMD -0.34, CI -0.6 to -0.06, I2 = 70%), but only in the short term. There was inadequate low-quality evidence to determine whether psychological therapies were more effective than control conditions at improving functioning in either the short term or long term. No trials of therapies for addressing health-related anxiety were identified and only two trials reported adverse effects; these were unrelated to psychological therapies. Overall, the evidence was of low to moderate quality, results were heterogeneous, and only one trial had an available protocol. AUTHORS' CONCLUSIONS: A limited number of trials of variable quality have been undertaken to assess whether psychological therapies are effective for treating anxiety and depression in children and adolescents with long-term physical conditions. According to the available evidence, therapies specifically designed to treat anxiety or depression (especially those based on principles of cognitive behaviour therapy (CBT)) may be more likely to work in children and adolescents who have mild to moderate levels of symptoms of these disorders, at least in the short term. There is a dearth of therapies specifically designed to treat health-related anxiety in this age group.

E-Health interventions for anxiety and depression in children and adolescents with long-term physical conditions.

BACKGROUND: Long-term physical conditions affect 10% to 12% of children and adolescents worldwide; these individuals are at greater risk of developing psychological problems, particularly anxiety and depression. Access to face-to-face treatment for such problems is often limited, and available interventions usually have not been tested with this population. As technology improves, e-health interventions (delivered via digital means, such as computers and smart phones and ranging from simple text-based programmes through to multimedia and interactive programmes, serious games, virtual reality and biofeedback programmes) offer a potential solution to address the psychological needs of this group of young people. OBJECTIVES: To assess the effectiveness of e-health interventions in comparison with attention placebos, psychological placebos, treatment as usual, waiting-list controls, or non-psychological treatments for treating anxiety and depression in children and adolescents with long-term physical conditions. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Group's Controlled Trials Register (CCMDTR to May 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 8, 2017), Web of Science (1900 - 18 August 2016, updated 31 August 2017) and Ovid MEDLINE, Embase, PsycINFO (cross-search 2016 to 18 Aug 2017). We hand-searched relevant conference proceedings, reference lists of included articles, and the grey literature to May 2016. We also searched international trial registries to identify unpublished or ongoing trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs), cluster-randomised trials, and cross-over trials of e-health interventions for treating any type of long-term physical condition in children and adolescents (aged 0 to 18 years), and that measured changes in symptoms or diagnoses of anxiety, depression, or subthreshold depression. We defined long-term physical conditions as those that were more than three-months' duration. We assessed symptoms of anxiety and depression using patient- or clinician-administered validated rating scales based on DSM III, IV or 5 (American Psychological Association 2013), or ICD 9 or 10 criteria (World Health Organization 1992). Formal depressive and anxiety disorders were diagnosed using structured clinical interviews. Attention placebo, treatment as usual, waiting list, psychological placebo, and other non-psychological therapies were eligible comparators. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed titles, abstracts, and full-text articles; discrepancies were resolved through discussion or addressed by a third author. When available, we used odds ratio (OR) to compare dichotomous data and standardised mean differences (SMD) to analyse continuous data, both with 95% confidence intervals (CI). We undertook meta-analysis when treatments, participants, and the underlying clinical question were adequately similar. Otherwise, we undertook a narrative analysis. MAIN RESULTS: We included five trials of three interventions (Breathe Easier Online, Web-MAP, and multimodal cognitive behavioural therapy (CBT)), which included 463 participants aged 10 to 18 years. Each trial contributed to at least one meta-analysis. Trials involved children and adolescents with long-term physical conditions, such as chronic headache (migraine, tension headache, and others), chronic pain conditions (abdominal, musculoskeletal, and others), chronic respiratory illness (asthma, cystic fibrosis, and others), and symptoms of anxiety or depression. Participants were recruited from community settings and hospital clinics in high income countries.For the primary outcome of change in depression symptoms versus any control, there was very low-quality evidence meaning that it could not be determined whether e-health interventions were clearly better than any comparator (SMD -0.06, 95% CI -0.35 to 0.23; five RCTs, 441 participants). For the primary outcome of change in anxiety symptoms versus any comparator, there was very low-quality evidence meaning that it could not be determined whether e-health interventions were clearly better than any comparator (SMD -0.07, 95% CI -0.29 to 0.14; two RCTs, 324 participants). For the primary outcome of treatment acceptability, there was very low-quality evidence that e-health interventions were less acceptable than any comparator (SMD 0.46, 95% CI 0.23 to 0.69; two RCTs, 304 participants).For the secondary outcome of quality of life, there was very low-quality evidence meaning that it could not be determined whether e-health interventions were clearly better than any comparator (SMD -0.83, 95% CI -1.53 to -0.12; one RCT, 34 participants). For the secondary outcome of functioning, there was very low-quality evidence meaning that it could not be determined whether e-health interventions were clearly better than any comparator (SMD -0.08, 95% CI -0.33 to 0.18; three RCTs, 368 participants). For the secondary outcome of status of long-term physical condition, there was very low-quality evidence meaning that it could not be determined whether e-health interventions were clearly better than any comparator (SMD 0.06, 95% CI -0.12 to 0.24; five RCTs, 463 participants).The risk of selection bias was considered low in most trials. However, the risk of bias due to inadequate blinding of participants or outcome assessors was considered unclear or high in all trials. Only one study had a published protocol; two trials had incomplete outcome data. All trials were conducted by the intervention developers, introducing another possible bias. No adverse effects were reported by any authors. AUTHORS' CONCLUSIONS: At present, the field of e-health interventions for the treatment of anxiety or depression in children and adolescents with long-term physical conditions is limited to five low quality trials. The very low-quality of the evidence means the effects of e-health interventions are uncertain at this time, especially in children aged under 10 years.Although it is too early to recommend e-health interventions for this clinical population, given their growing number, and the global improvement in access to technology, there appears to be room for the development and evaluation of acceptable and effective technologically-based treatments to suit children and adolescents with long-term physical conditions.

Comparative efficacy and tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis.

BACKGROUND: Major depressive disorder is one of the most common mental disorders in children and adolescents. However, whether to use pharmacological interventions in this population and which drug should be preferred are still matters of controversy. Consequently, we aimed to compare and rank antidepressants and placebo for major depressive disorder in young people. METHODS: We did a network meta-analysis to identify both direct and indirect evidence from relevant trials. We searched PubMed, the Cochrane Library, Web of Science, Embase, CINAHL, PsycINFO, LiLACS, regulatory agencies' websites, and international registers for published and unpublished, double-blind randomised controlled trials up to May 31, 2015, for the acute treatment of major depressive disorder in children and adolescents. We included trials of amitriptyline, citalopram, clomipramine, desipramine, duloxetine, escitalopram, fluoxetine, imipramine, mirtazapine, nefazodone, nortriptyline, paroxetine, sertraline, and venlafaxine. Trials recruiting participants with treatment-resistant depression, treatment duration of less than 4 weeks, or an overall sample size of less than ten patients were excluded. We extracted the relevant information from the published reports with a predefined data extraction sheet, and assessed the risk of bias with the Cochrane risk of bias tool. The primary outcomes were efficacy (change in depressive symptoms) and tolerability (discontinuations due to adverse events). We did pair-wise meta-analyses using the random-effects model and then did a random-effects network meta-analysis within a Bayesian framework. We assessed the quality of evidence contributing to each network estimate using the GRADE framework. This study is registered with PROSPERO, number CRD42015016023. FINDINGS: We deemed 34 trials eligible, including 5260 participants and 14 antidepressant treatments. The quality of evidence was rated as very low in most comparisons. For efficacy, only fluoxetine was statistically significantly more effective than placebo (standardised mean difference -0·51, 95% credible interval [CrI] -0·99 to -0·03). In terms of tolerability, fluoxetine was also better than duloxetine (odds ratio [OR] 0·31, 95% CrI 0·13 to 0·95) and imipramine (0·23, 0·04 to 0·78). Patients given imipramine, venlafaxine, and duloxetine had more discontinuations due to adverse events than did those given placebo (5·49, 1·96 to 20·86; 3·19, 1·01 to 18·70; and 2·80, 1·20 to 9·42, respectively). In terms of heterogeneity, the global I(2) values were 33·21% for efficacy and 0% for tolerability. INTERPRETATION: When considering the risk-benefit profile of antidepressants in the acute treatment of major depressive disorder, these drugs do not seem to offer a clear advantage for children and adolescents. Fluoxetine is probably the best option to consider when a pharmacological treatment is indicated. FUNDING: National Basic Research Program of China (973 Program).

Targeting mental health care attributes by diagnosis and clinical stage: the views of youth mental health clinicians.

OBJECTIVES: To explore the potential utility of clinical stage and mental disorder categories as a basis for determining which attributes of youth mental health care should be offered to which groups of young people. METHODS: In June 2017, we conducted an online survey of youth mental health clinicians that collected information on the participants' background and areas of expertise, then presented vignettes describing young people with different stages of six mental disorders (disorder-based vignettes were matched to participants' area of expertise). For each vignette, participants were asked to give a quantitative estimate of the proportion of young people with similar mental health problems they thought would clinically benefit from each of twelve attributes of mental health care (other than pharmacological or individual psychological therapies). Survey results were analysed as independent, disorder-based samples, using standard statistical tests of significance, and as a stratified sample using mixed-effects models. RESULTS: A total of 412 clinicians working in 32 countries participated in both parts of the survey. Respondents represented a broad range of clinical disciplines, settings and areas of expertise. Their estimated proportions of young people who would benefit from the mental health care attributes varied by clinical stage and disorder (eg, a mean of 93% [interquartile range (IQR), 90%-100%] of young people with Stage 2 psychosis were estimated to benefit from case management with a multidisciplinary team; while only 15% [IQR, 1%-25%] of young people with Stage 1b generalised anxiety disorder were estimated to benefit from collection and processing of biological samples). Neither the background of the respondents nor the sex of the characters in the vignettes significantly influenced the results. CONCLUSION: A combination of clinical stage and disorder information might be an appropriate basis for ensuring that the right attributes of early intervention mental health care are provided to the right young people at the right time. Policy and research priorities include trialling novel services, preferences research among young people, strengthening service responses to subthreshold disorders and promoting high-fidelity collection of clinical stage data in youth mental health settings.

Identifying attributes of care that may improve cost-effectiveness in the youth mental health service system.

OBJECTIVE: To identify attributes of youth mental health care for which there is evidence of potential cost-effectiveness. STUDY DESIGN: We performed a literature review of economic evaluations that examined both costs and outcomes for attributes of youth mental health care other than pharmacological or individual psychological therapies for full-threshold disorders. DATA SOURCES: We searched the United Kingdom National Health Service Economic Evaluations Database for evaluations published to the end of 2014; and MEDLINE, Google Scholar and the citation lists of relevant publications for peer-reviewed studies published in English since 1997. DATA SYNTHESIS: Forty economic evaluations met inclusion criteria. Psychosis was the mental disorder with the most developed economic evidence base, with good evidence of cost-effectiveness for first-episode psychosis services. There was a developing cost-effectiveness evidence base for other disorders. The most common attributes of the interventions examined in the included studies were the location of services, engagement and support of families, assessment, prevention, early intervention, group delivery format and information provision. We used our findings to formulate a list of attributes of youth mental health care that may be acceptable to young people and potentially cost-effective. CONCLUSION: There is at least suggestive cost-effectiveness evidence for a range of attributes of youth mental health care. Further economic research is needed to substantiate most cost-effectiveness findings and to improve targeting of care among young people. Future economic evaluations should examine costs from both societal and health care perspectives and incorporate evidence regarding young people's preferences.