Centre for Youth Mental Health - Research Publications

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    Comparative efficacy and tolerability of first-generation and newer-generation antidepressant medications for depressive disorders in children and adolescents: study protocol for a systematic review and network meta-analysis.
    Zhou, X ; Qin, B ; Whittington, C ; Cohen, D ; Liu, Y ; Del Giovane, C ; Michael, KD ; Zhang, Y ; Xie, P (BMJ, 2015-09-09)
    INTRODUCTION: Depressive disorders are among the most common psychiatric disorders in children and adolescents, and have adverse effects on their psychosocial functioning. Questions concerning the efficacy and safety of antidepressant medications in the treatment of depression in children and adolescents, led us to integrate the direct and indirect evidence using network meta-analysis to create hierarchies of these drugs. METHODS AND ANALYSIS: Seven databases with PubMed, EMBASE, the Cochrane Library, Web of Science, CINAHL, LiLACS and PsycINFO will be searched from 1966 to December 2013 (updated to May, 2015). There are no restrictions on language or type of publication. Randomised clinical trials assessing first-generation and newer-generation antidepressant medications against active comparator or placebo as acute treatment for depressive disorders in children and adolescents (under 18 years of age) will be included. The primary outcome for efficacy will be mean improvement in depressive symptoms, as measured by the mean change score of a depression rating scale from baseline to post-treatment. The tolerability of treatment will be defined as side effect discontinuation, as defined by the proportion of patients who discontinued treatment due to adverse events during the trial. We will also assess the secondary outcome for efficacy (response rate), acceptability (all-cause discontinuation) and suicide-related outcomes. We will perform the Bayesian network meta-analyses for all relative outcome measures. Subgroup analyses and sensitivity analyses will be conducted to assess the robustness of the findings. DISSEMINATION: The network meta-analysis will provide useful information on antidepressant treatment for child and adolescent depression. The results will be disseminated through peer-reviewed publication or conference presentations. TRIAL REGISTRATION NUMBER: PROSPERO CRD42015016023.
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    Open-access evidence database of controlled trials and systematic reviews in youth mental health
    De Silva, S ; Bailey, AP ; Parker, AG ; Montague, AE ; Hetrick, SE (WILEY, 2018-06)
    AIM: To present an update to an evidence-mapping project that consolidates the evidence base of interventions in youth mental health. To promote dissemination of this resource, the evidence map has been translated into a free online database (https://orygen.org.au/Campus/Expert-Network/Evidence-Finder or https://headspace.org.au/research-database/). Included studies are extensively indexed to facilitate searching. METHODS: A systematic search for prevention and treatment studies in young people (mean age 6-25 years) is conducted annually using Embase, MEDLINE, PsycINFO and the Cochrane Library. Included studies are restricted to controlled trials and systematic reviews published since 1980. RESULTS: To date, 221 866 publications have been screened, of which 2680 have been included in the database. Updates are conducted annually. CONCLUSIONS: This shared resource can be utilized to substantially reduce the amount of time involved with conducting literature searches. It is designed to promote the uptake of evidence-based practice and facilitate research to address gaps in youth mental health.
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    Development of an implementation guide to facilitate the roll-out of early intervention services for psychosis
    Hetrick, SE ; O'Connor, DA ; Stavely, H ; Hughes, F ; Pennell, K ; Killackey, E ; McGorry, PD (WILEY, 2018-12)
    AIM: Our aim was to develop an implementation guide that was informed by an analysis of context-specific barriers and enablers, behaviour change theory, as well as evidence about the effects of implementation interventions, for the establishment and scaling up of an early intervention model for psychosis (called Early Psychosis Prevention and Intervention Centre (EPPIC)). METHODS: We used a systematic approach involving four steps. First, the target behaviours of the EPPIC model for implementation were specified. Second, a consultation was undertaken to explore the barriers and enablers to undertaking these priority minimum standard clinical behaviours. Third, an implementation strategy that included a range of behaviour change techniques tailored to address the identified barriers was developed. Finally, a tool to assess whether those implementing the EPPIC model maintained fidelity to the implementation strategy was designed. RESULTS: We identified a range of barriers that could act to dilute the core components of the EPPIC model and compromise its implementation. An implementation strategy using theory and evidence-based strategies for behaviour change was designed to address these barriers. CONCLUSIONS: The process we used in the development of the implementation strategy provided a unique opportunity to consider the essential areas to cover, how to make information easily understandable and accessible while noting the complexity of issues involved in not only implementation, but also the scaling up of the EPPIC model for services.
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    A systematic review and meta-analysis of prospective transition from major depression to bipolar disorder
    Ratheesh, A ; Davey, C ; Hetrick, S ; Alvarez-Jimenez, M ; Voutier, C ; Bechdolf, A ; McGorry, PD ; Scott, J ; Berk, M ; Cotton, SM (WILEY, 2017-04)
    OBJECTIVE: Some people with major depressive disorder (MDD) may be at a pre-onset stage for bipolar disorder (BD), where early identification or prevention efforts may be feasible. We aimed to identify rates and characteristics predictive of transition to BD in prospective follow-up studies of people with MDD. METHODS: Using a systematic search strategy, we identified studies with a diagnostic ascertainment of MDD and BD of an adequate standard, and where the minimum length of follow-up was 6 months. We examined the incidence and point prevalence of BD and the pooled odds ratios (OR) for baseline predictors. RESULTS: From 5554 unique publications, 56 were included. Nearly a quarter of adults (22.5%) and adolescents with MDD followed up for a mean length of 12-18 years developed BD, with the greatest risk of transition being in the first 5 years. The meta-analysis identified that transition from MDD to BD was predicted by family history of BD (OR = 2.89, 95% CI: 2.01-4.14, N = 7), earlier age of onset of depression (g = -0.33, SE = 0.05, N = 6) and presence of psychotic symptoms (OR = 4.76, 95% CI: 1.79-12.66, N = 5). CONCLUSIONS: Participants with the identified risk factors merit closer observation and may benefit from prevention efforts, especially if outcomes broader than BD are considered.
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    Moderated online social therapy for depression relapse prevention in young people: pilot study of a "next generation' online intervention
    Rice, S ; Gleeson, J ; Davey, C ; Hetrick, S ; Parker, A ; Lederman, R ; Wadley, G ; Murray, G ; Herrman, H ; Chambers, R ; Russon, P ; Miles, C ; D'Alfonso, S ; Thurley, M ; Chinnery, G ; Gilbertson, T ; Eleftheriadis, D ; Barlow, E ; Cagliarini, D ; Toh, J-W ; McAlpine, S ; Koval, P ; Bendall, S ; Jansen, JE ; Hamilton, M ; McGorry, P ; Alvarez-Jimenez, M (WILEY, 2018-08)
    AIM: Implementation of targeted e-mental health interventions offers a promising solution to reducing the burden of disease associated with youth depression. A single-group pilot study was conducted to evaluate the acceptability, feasibility, usability and safety of a novel, moderated online social therapy intervention (entitled Rebound) for depression relapse prevention in young people. METHODS: Participants were 42 young people (15-25 years) (50% men; mean age = 18.5 years) in partial or full remission. Participants had access to the Rebound platform for at least 12 weeks, including the social networking, peer and clinical moderator and therapy components. RESULTS: Follow-up data were available for 39 (92.9%) participants. There was high system usage, with 3034 user logins (mean = 72.2 per user) and 2146 posts (mean = 51.1). Almost 70% of users had ≥10 logins over the 12 weeks, with 78.5% logging in over at least 2 months of the pilot. A total of 32 (84%) participants rated the intervention as helpful. There was significant improvement between the number of participants in full remission at baseline (n = 5; none of whom relapsed) relative to n = 19 at 12-week follow-up (P < 0.001). Six (14.3%) participants relapsed to full threshold symptoms at 12 weeks. There was a significant improvement to interviewer-rated depression scores (Montgomery-Asberg Depression Rating Scale (MADRS); P = 0.014, d = 0.45) and a trend for improved strength use (P = 0.088, d = 0.29). The single-group design and 12-week treatment phase preclude a full understanding of the clinical benefits of the Rebound intervention. CONCLUSIONS: The Rebound intervention was shown to be acceptable, feasible, highly usable and safe in young people with major depression.
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    Co-design of eHealth Interventions With Children and Young People.
    Thabrew, H ; Fleming, T ; Hetrick, S ; Merry, S (Frontiers Media SA, 2018)
    Co-design, defined as collective creativity across the entire design process, can lead to the development of interventions that are more engaging, satisfying, and useful to potential users. However, using this methodology within the research arena requires a shift from traditional practice. Co-design of eHealth interventions with children and young people has additional challenges. This review summarizes the applied core principles of co-design and recommends techniques for undertaking co-design with children and young people. Three examples of co-design during the development of eHealth interventions (Starship Rescue, a computer game for treating anxiety in children with long-term physical conditions, a self-monitoring app for use during treatment of depression in young people, and HABITS, the development of an emotional health and substance use app, and eHealth platform for young people) are provided to illustrate the value and challenges of this contemporary process.
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    Making decisions about treatment for young people diagnosed with depressive disorders: a qualitative study of clinicians' experiences
    Simmons, MB ; Hetrick, SE ; Jorm, AF (BMC, 2013-12-12)
    BACKGROUND: The imperative to provide effective treatment for young people diagnosed with depressive disorders is complicated by several factors including the unclear effectiveness of treatment options. Within this context, little is known about how treatment decisions are made for this population. METHODS: In order to explore the experiences and beliefs of clinicians about treatment decision making for this population, semi-structured, qualitative interviews were conducted with 22 psychiatrists, general practitioners and allied health professionals from health care settings including specialist mental health services and primary health care. Interviews were audio taped, transcribed verbatim and analysed using thematic analysis. RESULTS: Clinicians largely reported and endorsed a collaborative model of treatment decision making for youth depression, although several exceptions to this approach were also described (e.g., when risk issues were present), highlighting a need to adapt the decision-making style to the characteristics and needs of the client. A differentiation was made between the decision-making processes (e.g., sharing of information) and who makes the decision. Caregiver involvement was seen as optional, especially in situations where no caregivers were involved, but ideal and useful if the caregivers were supportive. Gaps between the type and amount of information clinicians wanted to give their clients and what they actually gave them were reported (e.g., having fact sheets on hand). A broad range of barriers to involving clients and caregivers in decision-making processes were described relating to four levels (client and caregiver, clinician, service and broader levels) and suggestions were given to help overcome these barriers, including up-to-date, accessible and relevant information. CONCLUSIONS: The current data support a collaborative model of treatment decision making for youth depression which: (1) focuses on the decision-making processes rather than who actually makes the decision; (2) is flexible to the individual needs and characteristics of the client; and (3) where caregiver involvement is optional. Shared decision making interventions and the use of decision aids should be considered for this area.
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    Characterizing neurocognitive impairment in young people with major depression: state, trait, or scar?
    Allott, K ; Fisher, CA ; Amminger, GP ; Goodall, J ; Hetrick, S (WILEY, 2016-10)
    BACKGROUND: Major depressive disorder (MDD) affects a quarter of adolescents and young adults and is associated with the greatest global burden of disease in this population. There is a growing literature, mostly in adults, showing that significant neurocognitive impairments are common in MDD. It remains unclear whether these impairments are pre-existing trait markers of MDD, state-related impairments that fluctuate with depressive symptoms, or 'scar' impairments that worsen with illness progression. The aim of this study is to provide a conceptual framework for understanding MDD and neurocognitive impairment in adolescence and young adulthood (ages 12-25 years). METHOD: Examination of the evidence for neurocognitive deficits as trait, state, and scar features of MDD according to different study designs (family studies, premorbid studies, current depression, remitted depression, and longitudinal studies with repeated assessment) was conducted. RESULTS: The few premorbid and family studies conducted in youth provide equivocal evidence for neurocognitive impairments as trait markers of MDD. The presence of state-based neurocognitive impairment remains unclear as evidence comes mostly from cross-sectional studies. There are a limited, but growing number of longitudinal studies with repeated neurocognitive assessment in youth. Studies that examined neurocognition prior to the onset of MDD and with long-term follow-up provide tentative evidence for neurocognitive scarring. CONCLUSION: Neurocognitive impairment is a feature of MDD in adolescents and young adults. To better understand the nature, timing, and pattern of impairment, longitudinal studies that examine neurocognition before and after the development of full-threshold MDD, including following recurrence are needed. This knowledge will have important implications for mechanisms, prevention, and treatment of MDD in youth.
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    Comparative efficacy and acceptability of psychotherapies for post-traumatic stress disorder in children and adolescents: study protocol for a systematic review and network meta analysis
    Zhang, Y ; Zhou, X ; Yang, L ; Hetrick, SE ; Weisz, JR ; Cuijpers, P ; Barth, J ; Del Giovane, C ; Yuan, S ; Cohen, D ; Gillies, D ; Jiang, X ; Teng, T ; Xie, P (BMJ PUBLISHING GROUP, 2018-03)
    INTRODUCTION: Post-traumatic stress disorder (PTSD) is common among children and adolescents who are exposed to trauma, and it is often associated with significant negative impacts on their psychosocial functioning and quality of life. Many types of psychotherapies have been found to be effective for PTSD in children and adolescents. However, due to the lack of direct comparisons between different psychotherapies, the hierarchy of treatment efficacy is still unclear. Therefore, we plan to conduct a systematic review and network meta-analysis to evaluate the efficacy and acceptability of various types of psychotherapies for PTSD in children and adolescents. METHODS AND ANALYSIS: A systematic search will be conducted among eight electronic databases, including PubMed, Cochrane, Embase, Web of Science, PsycINFO, Cumulative Index of Nursing and Allied Health, Published International Literature on Traumatic Stress (PILOTS) and ProQuest Dissertations, from inception to October 2017. Randomised controlled trials, regardless of language, publication year and publication type, comparing any psychotherapies for PTSD to any control condition or alternative treatment in children and adolescents (18 years old or less) diagnosed with full or subclinical PTSD will be included. Study duration and the number of treatment sessions will not be limited. The primary outcome will be PTSD symptom severity at post-treatment as measured by a rating scale reported by the child, parent or a clinician. The secondary outcomes will include: (1) efficacy at follow-up; (2) acceptability (all-cause discontinuation); (3) anxiety symptom severity; (4) depressive symptom severity and (5) quality of life and functional improvement. Bayesian network meta-analyses for all relative outcome measures will be performed. We will conduct subgroup and sensitivity network meta-analyses to determine whether the findings are affected by study characteristics. The quality of the evidence contributing to network estimates of the primary outcome will be evaluated by the Grading of Recommendations, Assessment, Development and Evaluations framework. ETHICS AND DISSEMINATION: No ethical issues are foreseen. The results will be published in a peer-reviewed journal, which will be disseminated electronically and in print. This network meta-analysis may be updated to inform and guide the clinical management of PTSD in children and adolescents. PROSPERO REGISTRATION NUMBER: CRD42016051786.
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    Comparative efficacy and tolerability of new-generation antidepressants for major depressive disorder in children and adolescents: protocol of an individual patient data meta-analysis
    Zhou, X ; Cipriani, A ; Furukawa, TA ; Cuijpers, P ; Zhang, Y ; Hetrick, SE ; Pu, J ; Yuan, S ; Del Giovane, C ; Xie, P (BMJ PUBLISHING GROUP, 2018-01)
    INTRODUCTION: Although previous conventional meta-analyses and network meta-analyses have provided some important findings about pharmacological treatments for children and adolescents with depressive disorders in the past decades, several questions still remain unsolved by the aggregate data from those meta-analyses. Individual participant data meta-analysis (IPD-MA) enables exploration of the impacts of individual characteristics on treatment effects, allowing matching of treatments to specific subgroups of patients. We will perform an IPD-MA to assess the efficacy and tolerability of new-generation antidepressants for major depressive disorder in children and adolescents. METHODS AND ANALYSIS: We will systematically search for all double-blind randomised controlled trials (RCTs) that have compared any new-generation antidepressant with placebo for the acute treatment of major depressive disorder in children and adolescents, in the following databases: PubMed, EMBASE, the Cochrane Library, PsycINFO, Web of Science, CINAHL, LILACS and ProQuest Dissertations. We will contact all corresponding authors of included RCTs and ask for their cooperation in this project by providing individual participant data from the original trials. The primary outcomes will include efficacy, measured as the mean change of depression symptoms by Children's Depression Rating Scale Revised (CDRS-R), and tolerability, measured as the proportion of patients who withdrew from the trials early due to adverse effects. The secondary outcomes will include response rates, remission rates, deterioration rate, all-cause discontinuation, suicidal-related outcomes and global functioning outcome. Using the raw de-identified study data, we will use mixed-effects logistic and linear regression models to perform the IPD-MAs. The risk of bias of included studies will be assessed using the Cochrane risk of bias tool. We will also detect the publication bias and effects of non-participation of eligible studies. DISSEMINATION: Ethical approval is not required given that informed consent has already been obtained from the patients by the trial investigators before the included trials were conducted. This study may have considerable implications for practice and help improve patient care. PROSPERO REGISTRATION NUMBER: CRD42016051657.