Centre for Youth Mental Health - Research Publications

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    'Prodromal' research and clinical services: The imperative for shared decision-making
    Simmons, MB ; Hetrick, SE (SAGE PUBLICATIONS LTD, 2012-01)
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    Interventions for preventing relapse and recurrence of a depressive disorder in children and adolescents
    Cox, GR ; Fisher, CA ; De Silva, S ; Phelan, M ; Akinwale, OP ; Simmons, MB ; Hetrick, SE (WILEY, 2012)
    BACKGROUND: Depressive disorders often begin during childhood or adolescence. There is a growing body of evidence supporting effective treatments during the acute phase of a depressive disorder. However, little is known about treatments for preventing relapse or recurrence of depression once an individual has achieved remission or recovery from their symptoms. OBJECTIVES: To determine the efficacy of early interventions, including psychological and pharmacological interventions, to prevent relapse or recurrence of depressive disorders in children and adolescents. SEARCH METHODS: We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) (to 1 June 2011). The CCDANCTR contains reports of relevant randomised controlled trials from The Cochrane Library (all years), EMBASE (1974 to date), MEDLINE (1950 to date) and PsycINFO (1967 to date). In addition we handsearched the references of all included studies and review articles. SELECTION CRITERIA: Randomised controlled trials using a psychological or pharmacological intervention, with the aim of preventing relapse or recurrence from an episode of major depressive disorder (MDD) or dysthymic disorder (DD) in children and adolescents were included. Participants were required to have been diagnosed with MDD or DD according to DSM or ICD criteria, using a standardised and validated assessment tool. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed all trials for inclusion in the review, extracted trial and outcome data, and assessed trial quality. Results for dichotomous outcomes are expressed as odds ratio and continuous measures as mean difference or standardised mean difference. We combined results using random-effects meta-analyses, with 95% confidence intervals. We contacted lead authors of included trials and requested additional data where possible. MAIN RESULTS: Nine trials with 882 participants were included in the review. In five trials the outcome assessors were blind to the participants' intervention condition and in the remainder of trials it was unclear. In the majority of trials, participants were either not blind to their intervention condition, or it was unclear whether they were or not. Allocation concealment was also unclear in the majority of trials. Although all trials treated participants in an outpatient setting, the designs implemented in trials was diverse, which limits the generalisability of the results. Three trials indicated participants treated with antidepressant medication had lower relapse-recurrence rates (40.9%) compared to those treated with placebo (66.6%) during a relapse prevention phase (odds ratio (OR) 0.34; 95% confidence interval (CI) 0.18 to 0.64, P = 0.02). One trial that compared a combination of psychological therapy and medication to medication alone favoured a combination approach over medication alone, however this result did not reach statistical significance (OR 0.26; 95% CI 0.06 to 1.15). The majority of trials that involved antidepressant medication reported adverse events including suicide-related behaviours. However, there were not enough data to show which treatment approach results in the most favourable adverse event profile. AUTHORS' CONCLUSIONS: Currently, there is little evidence to conclude which type of treatment approach is most effective in preventing relapse or recurrence of depressive episodes in children and adolescents. Limited trials found that antidepressant medication reduces the chance of relapse-recurrence in the future, however, there is considerable diversity in the design of trials, making it difficult to compare outcomes across studies. Some of the research involving psychological therapies is encouraging, however at present more trials with larger sample sizes need to be conducted in order to explore this treatment approach further.
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    Risk factors for relapse following treatment for first episode psychosis: A systematic review and meta-analysis of longitudinal studies
    Alvarez-Jimenez, M ; Priede, A ; Hetrick, SE ; Bendall, S ; Killackey, E ; Parker, AG ; McGorry, PD ; Gleeson, JF (ELSEVIER, 2012-08)
    BACKGROUND: Preventing relapse is an essential element of early intervention in psychosis, but relevant risk factors and precise relapse rates remain to be clarified. The aim of this study was to systematically compile and analyse risk factors for and rates of relapse in the early course of psychosis. METHODS: Systematic review and meta-analysis of English and non-English language, peer-reviewed, longitudinal studies, with a minimum 12-month follow-up and at least 80% of participants diagnosed with a first episode of psychosis (FEP) that reported risk factors for relapse. RESULTS: Of 153 potentially relevant articles, 29 were included in the study. Pooled prevalence of relapse of positive symptoms was 28% (range=12-47%), 43% (35-54%), 54% (40-63%) at 1, 1.5-2, and 3 years follow-up, in that order. A total of 109 predictors were analysed, with 24 being assessed in at least 3 studies. Of those, 20 predictors could be extracted for meta-analysis. Medication non-adherence, persistent substance use disorder, carers' critical comments (but not overall expressed emotion) and poorer premorbid adjustment, increased the risk for relapse 4-fold, 3-fold, 2.3-fold and 2.2-fold, respectively. CONCLUSIONS: Clinical variables and general demographic variables have little impact on relapse rates. Conversely, non-adherence with medication, persistent substance use disorder, carers' criticism and poorer premorbid adjustment significantly increase the risk for relapse in FEP. Future studies need to address the methodological limitations of the extant research (e.g. definition of relapse), focus on the identification of protective factors and evaluate theoretically derived models of relapse.
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    Quality of information sources about mental disorders: a comparison of Wikipedia with centrally controlled web and printed sources
    Reavley, NJ ; Mackinnon, AJ ; Morgan, AJ ; Alvarez-Jimenez, M ; Hetrick, SE ; Killackey, E ; Nelson, B ; Purcell, R ; Yap, MBH ; Jorm, AF (CAMBRIDGE UNIV PRESS, 2012-08)
    BACKGROUND: Although mental health information on the internet is often of poor quality, relatively little is known about the quality of websites, such as Wikipedia, that involve participatory information sharing. The aim of this paper was to explore the quality of user-contributed mental health-related information on Wikipedia and compare this with centrally controlled information sources. METHOD: Content on 10 mental health-related topics was extracted from 14 frequently accessed websites (including Wikipedia) providing information about depression and schizophrenia, Encyclopaedia Britannica, and a psychiatry textbook. The content was rated by experts according to the following criteria: accuracy, up-to-dateness, breadth of coverage, referencing and readability. RESULTS: Ratings varied significantly between resources according to topic. Across all topics, Wikipedia was the most highly rated in all domains except readability. CONCLUSIONS: The quality of information on depression and schizophrenia on Wikipedia is generally as good as, or better than, that provided by centrally controlled websites, Encyclopaedia Britannica and a psychiatry textbook.
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    Psychological therapies versus antidepressant medication, alone and in combination for depression in children and adolescents.
    Cox, GR ; Callahan, P ; Churchill, R ; Hunot, V ; Merry, SN ; Parker, AG ; Hetrick, SE ; Cox, GR (John Wiley & Sons, Ltd, 2012-11-14)
    BACKGROUND: Depressive disorders are common in children and adolescents and, if left untreated, are likely to recur in adulthood. Depression is highly debilitating, affecting psychosocial, family and academic functioning. OBJECTIVES: To evaluate the effectiveness of psychological therapies and antidepressant medication, alone and in combination, for the treatment of depressive disorder in children and adolescents. We have examined clinical outcomes including remission, clinician and self reported depression measures, and suicide-related outcomes. SEARCH METHODS: We searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to 11 November 2011. This register contains reports of relevant randomised controlled trials (RCTs) from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date). SELECTION CRITERIA: RCTs were eligible for inclusion if they compared i) any psychological therapy with any antidepressant medication, or ii) a combination of psychological therapy and antidepressant medication with a psychological therapy alone, or an antidepressant medication alone, or iii) a combination of psychological therapy and antidepressant medication with a placebo or 'treatment as usual', or (iv) a combination of psychological therapy and antidepressant medication with a psychological therapy or antidepressant medication plus a placebo.We included studies if they involved participants aged between 6 and 18 years, diagnosed by a clinician as having Major Depressive Disorder (MDD) based on Diagnostic and Statistical Manual (DSM) or International Classification of Diseases (ICD) criteria. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, extracted data and assessed the quality of the studies. We applied a random-effects meta-analysis, using the odds ratio (OR) to describe dichotomous outcomes, mean difference (MD) to describe continuous outcomes when the same measures were used, and standard mean difference (SMD) when outcomes were measured on different scales. MAIN RESULTS: We included ten studies, involving 1235 participants in this review. Studies recruited participants with different severities of disorder and with a variety of comorbid disorders, including anxiety and substance use disorder, therefore limiting the comparability of the results. Regarding the risk of bias in studies, half the studies had adequate allocation concealment (there was insufficient information to determine allocation concealment in the remainder), outcome assessors were blind to the participants' intervention in six studies, and in general, studies reported on incomplete data analysis methods, mainly using intention-to-treat (ITT) analyses. For the majority of outcomes there were no statistically significant differences between the interventions compared. There was limited evidence (based on two studies involving 220 participants) that antidepressant medication was more effective than psychotherapy on measures of clinician defined remission immediately post-intervention (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.27 to 0.98), with 67.8% of participants in the medication group and 53.7% in the psychotherapy group rated as being in remission. There was limited evidence (based on three studies involving 378 participants) that combination therapy was more effective than antidepressant medication alone in achieving higher remission from a depressive episode immediately post-intervention (OR 1.56, 95% CI 0.98 to 2.47), with 65.9% of participants treated with combination therapy and 57.8% of participants treated with medication, rated as being in remission. There was no evidence to suggest that combination therapy was more effective than psychological therapy alone, based on clinician rated remission immediately post-intervention (OR 1.82, 95% CI 0.38 to 8.68).Suicide-related Serious Adverse Events (SAEs) were reported in various ways across studies and could not be combined in meta-analyses. However suicidal ideation specifically was generally measured and reported using standardised assessment tools suitable for meta-analysis. In one study involving 188 participants, rates of suicidal ideation were significantly higher in the antidepressant medication group (18.6%) compared with the psychological therapy group (5.4%) (OR 0.26, 95% CI 0.09 to 0.72) and this effect appeared to remain at six to nine months (OR 1.27, 95% CI 0.68 to 2.36), with 13.6% of participants in the medication group and 3.9% of participants in the psychological therapy group reporting suicidal ideation. It was unclear what the effect of combination therapy was compared with either antidepressant medication alone or psychological therapy alone on rates of suicidal ideation. The impact of any of the assigned treatment packages on drop out was also mostly unclear across the various comparisons in the review.Limited data and conflicting results based on other outcome measures make it difficult to draw conclusions regarding the effectiveness of any specific intervention based on these outcomes. AUTHORS' CONCLUSIONS: There is very limited evidence upon which to base conclusions about the relative effectiveness of psychological interventions, antidepressant medication and a combination of these interventions. On the basis of the available evidence, the effectiveness of these interventions for treating depressive disorders in children and adolescents cannot be established. Further appropriately powered RCTs are required.
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    Predicting Suicidal Risk in a Cohort of Depressed Children and Adolescents
    Hetrick, SE ; Parker, AG ; Robinson, J ; Hall, N ; Vance, A (HOGREFE & HUBER PUBLISHERS, 2012)
    BACKGROUND: In children and adolescents with a depressive disorder, predicting who will also go on to exhibit suicide-related behaviors (SRBs), including suicide attempt or self-harm, is a key challenge facing clinicians. AIMS: To investigate the relative contributions of depressive disorder severity, hopelessness, family dysfunction, and perceived social support to the risk of suicide-related behaviors. METHODS: This was a cross-sectional study of a group of 10-16-year-olds with major depressive disorders and dysthymic disorder. RESULTS: Child-rated depressive disorder symptom severity emerged as the greatest predictor of risk. Hopelessness and family dysfunction were also significant predictors of SRBs. In combination these variables were strong predictors, accounting for 66% of the variance. This is a cross-sectional study design, rather than longitudinal, therefore risk prediction over time was not possible. CONCLUSIONS: Understanding the child and adolescents depressive disorder symptom severity from their perspective, their level of hopelessness, as well as their family context is critical in understanding the risk of SRBs. These findings may help to provide direction for targeted interventions to address these clinical risk factors.
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    Newer generation antidepressants for depressive disorders in children and adolescents
    Hetrick, SE ; McKenzie, JE ; Cox, GR ; Simmons, MB ; Merry, SN (WILEY, 2012)
    BACKGROUND: Depressive disorders are common in young people and are associated with significant negative impacts. Newer generation antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), are often used, however evidence of their effectiveness in children and adolescents is not clear. Furthermore, there have been warnings against their use in this population due to concerns about increased risk of suicidal ideation and behaviour. OBJECTIVES: To determine the efficacy and adverse outcomes, including definitive suicidal behaviour and suicidal ideation, of newer generation antidepressants compared with placebo in the treatment of depressive disorders in children and adolescents. SEARCH METHODS: For this update of the review, we searched the Cochrane Depression, Anxiety and Neurosis Review Group's Specialised Register (CCDANCTR) to October 2011. The CCDANCTR includes relevant randomised controlled trials from the following bibliographic databases: CENTRAL (the Cochrane Central Register of Controlled Trials) (all years), EMBASE (1974 -), MEDLINE (1950 -) and PsycINFO (1967 -). We searched clinical trial registries and pharmaceutical company websites. We checked reference lists of included trials and other reviews, and sent letters to key researchers and the pharmaceutical companies of included trials from January to August 2011. SELECTION CRITERIA: Published and unpublished randomised controlled trials (RCTs), cross-over trials and cluster trials comparing a newer generation antidepressant with a placebo in children and adolescents aged 6 to 18 years old and diagnosed with a depressive disorder were eligible for inclusion. In this update, we amended the selection criteria to include newer generation antidepressants rather than SSRIs only. DATA COLLECTION AND ANALYSIS: Two or three review authors selected the trials, assessed their quality, and extracted trial and outcome data. We used a random-effects meta-analysis. We used risk ratio (RR) to summarise dichotomous outcomes and mean difference (MD) to summarise continuous measures. MAIN RESULTS: Nineteen trials of a range of newer antidepressants compared with placebo, containing 3335 participants, were included. The trials excluded young people at high risk of suicide and many co-morbid conditions and the participants are likely to be less unwell than those seen in clinical practice. We judged none of these trials to be at low risk of bias, with limited information about many aspects of risk of bias, high drop out rates and issues regarding measurement instruments and the clinical usefulness of outcomes, which were often variously defined across trials. Overall, there was evidence that those treated with an antidepressant had lower depression severity scores and higher rates of response/remission than those on placebo. However, the size of these effects was small with a reduction in depression symptoms of 3.51 on a scale from 17 to 113 (14 trials; N = 2490; MD -3.51; 95% confidence interval (CI) -4.55 to -2.47). Remission rates increased from 380 per 1000 to 448 per 1000 for those treated with an antidepressant. There was evidence of an increased risk (58%) of suicide-related outcome for those on antidepressants compared with a placebo (17 trials; N = 3229; RR 1.58; 95% CI 1.02 to 2.45). This equates to an increased risk in a group with a median baseline risk from 25 in 1000 to 40 in 1000. Where rates of adverse events were reported, this was higher for those prescribed an antidepressant. There was no evidence that the magnitude of intervention effects (compared with placebo) were modified by individual drug class. AUTHORS' CONCLUSIONS: Caution is required in interpreting the results given the methodological limitations of the included trials in terms of internal and external validity. Further, the size and clinical meaningfulness of statistically significant results are uncertain. However, given the risks of untreated depression in terms of completed suicide and impacts on functioning, if a decision to use medication is agreed, then fluoxetine might be the medication of first choice given guideline recommendations. Clinicians need to keep in mind that there is evidence of an increased risk of suicide-related outcomes in those treated with antidepressant medications.
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    Is there a gap between recommended and 'real world' practice in the management of depression in young people? A medical file audit of practice
    Hetrick, SE ; Thompson, A ; Yuen, K ; Finch, S ; Parker, AG (BMC, 2012-06-27)
    BACKGROUND: Literature has shown that dissemination of guidelines alone is insufficient to ensure that guideline recommendations are incorporated into every day clinical practice. METHODS: We aimed to investigate the gaps between guideline recommendations and clinical practice in the management of young people with depression by undertaking an audit of medical files in a catchment area public mental health service for 15 to 25 year olds in Melbourne, Australia. RESULTS: The results showed that the assessment and recording of depression severity to ensure appropriate treatment planning was not systematic nor consistent; that the majority of young people (74.5%) were prescribed an antidepressant before an adequate trial of psychotherapy was undertaken and that less than 50% were monitored for depression symptom improvement and antidepressant treatment emergent suicide related behaviours (35% and 30% respectively). Encouragingly 92% of first line prescriptions for those aged 18 years or under who were previously antidepressant-naïve was for fluoxetine as recommended. CONCLUSIONS: This research has highlighted the need for targeted strategies to ensure effective implementation. These strategies might include practice system tools that allow for systematic monitoring of depression symptoms and adverse side effects, particularly suicide related behaviours. Additionally, youth specific psychotherapy that incorporates the most effective components for this age group, delivered in a youth friendly way would likely aid effective implementation of guideline recommendations for engagement in an adequate trial of psychotherapy before medication is initiated.
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    Evidence map of prevention and treatment interventions for depression in young people.
    Callahan, P ; Liu, P ; Purcell, R ; Parker, AG ; Hetrick, SE (Hindawi Limited, 2012)
    Introduction. Depression in adolescents and young people is associated with reduced social, occupational, and interpersonal functioning, increases in suicide and self-harm behaviours, and problematic substance use. Age-appropriate, evidence-based treatments are required to provide optimal care. Methods. "Evidence mapping" methodology was used to quantify the nature and distribution of the extant high-quality research into the prevention and treatment of depression in young people across psychological, medical, and other treatment domains. Results. Prevention research is dominated by cognitive-behavioral- (CBT-) based interventions. Treatment studies predominantly consist of CBT and SSRI medication trials, with few trials of other psychological interventions or complementary/alternative treatments. Quality studies on relapse prevention and treatment for persistent depression are distinctly lacking. Conclusions. This map demonstrates opportunities for future research to address the numerous evidence gaps for interventions to prevent or treat depression in young people, which are of interest to clinical researchers, policy makers, and funding bodies.
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    Atypical antipsychotics for disruptive behaviour disorders in children and youths.
    Loy, JH ; Merry, SN ; Hetrick, SE ; Stasiak, K ; Loy, JH (John Wiley & Sons, Ltd, 2012-09-12)
    BACKGROUND: Disruptive behaviour disorders include conduct disorder, oppositional defiant disorder and disruptive behaviour not otherwise specified. Attention deficit hyperactivity disorder (ADHD) is frequently associated with disruptive behaviour disorders. The difficulties associated with disruptive behaviour disorders are demonstrated through aggression and severe behavioural problems. These often result in presentation to psychiatric services and may be treated with medications such as atypical antipsychotics. There is increasing evidence of a significant rise in the use of atypical antipsychotics for treating disruptive behaviour disorders in child and adolescent populations. OBJECTIVES: To evaluate the effect and safety of atypical antipsychotics, compared to placebo, for treating disruptive behaviour disorders in children and youths.  SEARCH METHODS: We searched the following databases in August 2011: CENTRAL (2011, Issue 3), MEDLINE (1948 to August Week 1), EMBASE (1980 to 2011 Week 32), PsycINFO (1806 to August Week 2 2011), CINAHL (1937 to current), ClinicalTrials.gov (searched 15 August 2011), Australian New Zealand Clinical Trials Registry (ANZCTR) (searched 15 August 2011), CenterWatch (searched 15 August 2011) and ICTRP (searched 15 August 2011). SELECTION CRITERIA: We included randomised controlled trials with children and youths up to and including the age of 18, in any setting, with a diagnosis of a disruptive behaviour disorder. We included trials where participants had a comorbid diagnosis of attention deficit hyperactivity disorder, major depression or an anxiety disorder. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies and disagreements were resolved by discussion. Two review authors extracted data independently. One review author entered data into Review Manager software and another checked it. We contacted trial authors for information about adverse effects and to provide missing data. MAIN RESULTS: We included eight randomised controlled trials, spanning 2000 to 2008. Seven assessed risperidone and one assessed quetiapine. Three of the studies were multicentre. Seven trials assessed acute efficacy and one assessed time to symptom recurrence over a six-month maintenance period.We performed meta-analyses for the primary outcomes of aggression, conduct problems and weight changes but these were limited by the available data as different trials reported either mean change scores (average difference) or final/post-intervention raw scores and used different outcome measures. We also evaluated each individual trial's treatment effect size where possible, using Hedges' g.For aggression, we conducted two meta-analyses. The first included three trials (combined n = 238) using mean difference (MD) on the Aberrant Behaviour Checklist (ABC) Irritability subscale. Results yielded a final mean score with treatment that was 6.49 points lower than the post-intervention mean score with placebo (95% confidence interval (CI) -8.79 to -4.19). The second meta-analysis on aggression included two trials (combined n = 57) that employed two different outcome measures (Overt Aggression Scale (modified) (OAS-M) and OAS, respectively) and thus we used a standardised mean difference. Results yielded an effect estimate of -0.18 (95% CI -0.70 to 0.34), which was statistically non-significant.We also performed two meta-analyses for conduct problems. The first included two trials (combined n = 225), both of which employed the Nisonger Child Behaviour Rating Form - Conduct Problem subscale (NCBRF-CP). The results yielded a final mean score with treatment that was 8.61 points lower than that with placebo (95% CI -11.49 to -5.74). The second meta-analysis on conduct problems included two trials (combined n = 36), which used the Conners' Parent Rating Scale - Conduct Problem subscale (CPRS-CP). Results yielded a mean score with treatment of 12.67 lower than with placebo (95% CI -37.45 to 12.11), which was a statistically non-significant result.With respect to the side effect of weight gain, a meta-analysis of two studies (combined n = 138) showed that participants on risperidone gained on average 2.37 kilograms more than those in the placebo group over the treatment period (MD 2.37; 95% CI 0.26 to 4.49).For individual trials, there was a range of effect sizes (ranging from small to large) for risperidone reducing aggression and conduct problems. The precision of the estimate of the effect size varied between trials. AUTHORS' CONCLUSIONS: There is some limited evidence of efficacy of risperidone reducing aggression and conduct problems in children aged 5 to 18 with disruptive behaviour disorders in the short term.For aggression, the difference in scores of 6.49 points on the ABC Irritability subscale (range 0 to 45) may be clinically significant. For conduct problems, the difference in scores of 8.61 points on the NCBRF-CP (range 0 to 48) is likely to be clinically significant.Caution is required due to the limitations of the evidence and the small number of relevant high-quality studies. The findings from the one study assessing impact in the longer term suggest that the effects are maintained to some extent (small effect size) for up to six months. Inadequately powered studies produced non-significant results. The evidence is restricted by heterogeneity of the population (including below average and borderline IQ), and methodological issues in some studies, such as use of enriched designs and risk of selection bias. No study addressed the issue of pre-existing/concurrent psychosocial interventions, and comorbid stimulant medication and its dosage was only partially addressed. There is currently no evidence to support the use of quetiapine for disruptive behaviour disorders in children and adolescents.It is uncertain to what degree the efficacy found in clinical trials will translate into real life clinical practice. Participants in the studies were recruited from clinical services but those who agree to take part in the clinical trials are a subset of the overall population presenting for care. There are no research data for children under five years of age. Further high-quality research is required with large samples of clinically representative youths and long-term follow-up to replicate current findings.