Centre for Youth Mental Health - Research Publications
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ItemTreatment-resistant depression in adolescents: is the addition of cognitive behavioral therapy of benefit?(DOVE MEDICAL PRESS LTD, 2011)BACKGROUND: Many young people with major depression fail first-line treatments. Treatment-resistant depression has various definitions in the literature but typically assumes nonresponse to medication. In young people, cognitive behavioral therapy (CBT) is the recommended first-line intervention, thus the definition of treatment resistance should be expanded. Therefore, our aim was to synthesize the existing evidence of any interventions for treatment-resistant depression, broadly defined, in children and adolescents and to investigate the effectiveness of CBT in this context. METHODS: We used Cochrane Collaboration methodology, with electronic searches of Medline, PsycINFO, Embase, and the Cochrane Depression Anxiety and Neurosis Group trials registers. Only randomized controlled trials were included, and were assessed for risk of bias. Meta- analysis was undertaken where possible and appropriate. RESULTS: Of 953 articles retrieved, four trials were eligible for inclusion. For one study, only the trial registration document was available, because the study was never completed. All other studies were well conducted with a low risk of bias, although one study had a high dropout rate. Two studies assessed the effect of adding CBT to medication. While an assertive trial of antidepressants does appear to lead to benefit, when compared with placebo, there was no significant advantage, in either study, or in a meta-analysis of data from these trials, that clearly demonstrated an additional benefit of CBT. The third trial showed little advantage of a tricyclic antidepressant over placebo in the context of an inpatient admission. CONCLUSION: Few randomized controlled trials have investigated interventions for treatment-resistant depression in young people, and results from these show modest benefit from antidepressants with no additional benefit over medication from CBT. Overall, there is a lack of evidence about effective interventions to treat young people who have failed to respond to evidence-based interventions for depression. Research in this area is urgently required.
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ItemInterventions for preventing relapse and recurrence of a depressive disorder in children and adolescents(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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ItemPsychological therapies versus antidepressant medication, alone and in combination for depression in children and adolescents.(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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ItemNewer generation antidepressants for depressive disorders in children and adolescents(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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ItemThe effectiveness of structural interventions at suicide hotspots: a meta-analysis(OXFORD UNIV PRESS, 2013-04)BACKGROUND: Certain sites have gained notoriety as 'hotspots' for suicide by jumping. Structural interventions (e.g. barriers and safety nets) have been installed at some of these sites. Individual studies examining the effectiveness of these interventions have been underpowered. METHOD: We conducted a meta-analysis, pooling data from nine studies. RESULTS: Following the interventions, there was an 86% reduction in jumping suicides per year at the sites in question (95% CI 79% to 91%). There was a 44% increase in jumping suicides per year at nearby sites (95% CI 15% to 81%), but the net gain was a 28% reduction in all jumping suicides per year in the study cities (95% CI 13% to 40%). CONCLUSIONS: Structural interventions at 'hotspots' avert suicide at these sites. Some increases in suicide are evident at neighbouring sites, but there is an overall gain in terms of a reduction in all suicides by jumping.
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ItemSuicide Clusters in Young People Evidence for the Effectiveness of Postvention Strategies(HOGREFE & HUBER PUBLISHERS, 2012)BACKGROUND: Suicide clusters have commonly been documented in adolescents and young people. AIMS: The current review conducts a literature search in order to identify and evaluate postvention strategies that have been employed in response to suicide clusters in young people. METHODS: Online databases, gray literature, and Google were searched for relevant articles relating to postvention interventions following a suicide cluster in young people. RESULTS: Few studies have formally documented response strategies to a suicide cluster in young people, and at present only one has been longitudinally evaluated. However, a number of strategies show promise, including: developing a community response plan; educational/psychological debriefings; providing both individual and group counseling to affected peers; screening high risk individuals; responsible media reporting of suicide clusters; and promotion of health recovery within the community to prevent further suicides. CONCLUSIONS: There is a gap in formal evidence-based guidelines detailing appropriate postvention response strategies to suicide clusters in young people. The low-frequency nature of suicide clusters means that long-term systematic evaluation of response strategies is problematic. However, some broader suicide prevention strategies could help to inform future suicide cluster postvention responses.
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ItemInterventions to reduce suicides at suicide hotspots: a systematic review(BMC, 2013-03-09)BACKGROUND: 'Suicide hotspots' include tall structures (for example, bridges and cliffs), railway tracks, and isolated locations (for example, rural car parks) which offer direct means for suicide or seclusion that prevents intervention. METHODS: We searched Medline for studies that could inform the following question: 'What interventions are available to reduce suicides at hotspots, and are they effective?' RESULTS: There are four main approaches: (a) restricting access to means (through installation of physical barriers); (b) encouraging help-seeking (by placement of signs and telephones); (c) increasing the likelihood of intervention by a third party (through surveillance and staff training); and (d) encouraging responsible media reporting of suicide (through guidelines for journalists). There is relatively strong evidence that reducing access to means can avert suicides at hotspots without substitution effects. The evidence is weaker for the other approaches, although they show promise. CONCLUSIONS: More well-designed intervention studies are needed to strengthen this evidence base.