Treatment-resistant depression in adolescents: is the addition of cognitive behavioral therapy of benefit?

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

Evidence Map of Prevention and Treatment Interventions for Depression in Young People

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

Evidence Map of Prevention and Treatment Interventions for Depression in Young People

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

The experience of young people receiving cognitive behavioural therapy for major depression : A qualitative study

Aim Major depressive disorder (MDD) has far reaching impacts for young people, their families and society. Cognitive behavioural therapy (CBT) is one of the first-line treatments for young people experiencing MDD; however, there is limited research examining how young people with MDD experience CBT. The aim of this study was to explore their experience and their views of this intervention. Methods We employed a qualitative research design, with semi-structured interviews and thematic analysis. Eight participants aged between 17 and 24 years who received CBT for MDD in a randomized controlled trial were recruited. Results Five themes were identified: the importance of relationship with clinician; the range of useful components within CBT; the ability for CBT to accommodate different techniques and presenting issues; the importance of checking in with clients during the process of therapy; and the impacts of MDD on therapy. Conclusions The findings highlight the importance of clinicians having a youth friendly and collaborative approach that allows a modular delivery of a range of CBT techniques to suit the client's presenting issue and formulation. There is a need to continually check how young people are responding to interventions, and to be aware of potential cognitive deficits and adjust therapy accordingly. This is a small study that provides insight into how young people with MDD experience CBT and avenues to explore for tailoring provision of CBT to enhance the therapeutic experience for this population

Is there a gap between recommended and ‘real world’ practice in the management of depression in young people? : a medical file audit of practice

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

The effectiveness of simple psychological and exercise interventions for high prevalence mental health problems in young people: a factorial randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>The prevalence of mental illness in young people is the highest of any age group, with the onset of depression, anxiety and substance use peaking between 18 and 24 years. Effective treatments that target sub-threshold or mild to moderate levels of disorder in young people are required to reduce the risk of persistence and recurrence. The aims of this study are to evaluate whether treatments that are less intensive than cognitive-behaviour therapy, such as problem solving therapy and exercise treatments, are acceptable and effective in managing depression and anxiety symptoms in young people and to identify possible attributes in those who are likely to respond to these treatments.</p> <p>Methods/design</p> <p>This is a factorial randomised controlled trial conducted at a large, metropolitan youth mental health service. Participants are young help-seekers aged 15-25 years with sub-threshold or mild to moderate levels of depression and anxiety (with or without comorbid substance use). The interventions comprise 4 treatment combinations delivered by psychologists over 6 sessions on a weekly basis: a psychological intervention (problem solving therapy versus supportive counselling) and an exercise intervention (behavioural exercise versus psychoeducation). Structured assessments occur at baseline, mid-point, end-point (6 weeks) and at a 6- and 12-month follow-up. The primary outcomes are depression and anxiety symptoms as measured by the Beck Depression and Anxiety Inventories. Secondary outcomes include remission (defined as no longer meeting the diagnostic criteria for a disorder if threshold level was reached at baseline, or no longer scoring in the clinical range on scale scores if sub-threshold at baseline), substance use, and functioning.</p> <p>Discussion</p> <p>The effectiveness of less complex psychological and exercise interventions in young help-seekers with sub-threshold or mild to moderate presentations of high prevalence disorders is yet to be explored. This study has been designed to examine the effectiveness of these interventions delivered alone, or in combination, in a youth-specific service. If effective, the interventions have the potential to prevent the progression of early symptoms and distress to later and potentially more serious stages of mental disorder and reduce the likelihood of ongoing problems associated with the risk of persistence and recurrence.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry <a href="http://www.anzctr.org.au/ACTRN12608000550303.aspx">ACTRN12608000550303</a></p

School-based interventions to prevent anxiety, depression and conduct disorders in children and young people:a systematic review, network meta-analysis and economic evaluation

Background: Schools in the UK increasingly have to respond to anxiety, depression and conduct disorder as key causes of morbidity in children and young people. Objective: The objective was to assess the comparative effectiveness of educational setting-based interventions for the prevention of anxiety, depression and conduct disorder in children and young people. Design: This study comprised a systematic review, a network meta-analysis and an economic evaluation. Data sources: The databases MEDLINE, EMBASE™ (Elsevier, Amsterdam, the Netherlands), PsycInfo® (American Psychological Association, Washington, DC, USA) and Cochrane Central Register of Controlled Trials (CENTRAL) were searched to 4 April 2018, and the NHS Economic Evaluation Database (NHS EED) was searched on 22 May 2019 for economic evaluations. No language or date filters were applied. Main outcomes: The main outcomes were post-intervention self-reported anxiety, depression or conduct disorder symptoms. Review methods: Randomised/quasi-randomised trials of universal or targeted interventions for the prevention of anxiety, depression or conduct disorder in children and young people aged 4–18 years were included. Screening was conducted independently by two reviewers. Data extraction was conducted by one reviewer and checked by a second. Intervention- and component-level network meta-analyses were conducted in OpenBUGS. A review of the economic literature and a cost–consequence analysis were conducted. Results: A total of 142 studies were included in the review, and 109 contributed to the network meta-analysis. Of the 109 studies, 57 were rated as having an unclear risk of bias for random sequence generation and allocation concealment. Heterogeneity was moderate. In universal secondary school settings, mindfulness/relaxation interventions [standardised mean difference (SMD) –0.65, 95% credible interval (CrI) –1.14 to –0.19] and cognitive–behavioural interventions (SMD –0.15, 95% CrI –0.34 to 0.04) may be effective for anxiety. Cognitive–behavioural interventions incorporating a psychoeducation component may be effective (SMD –0.30, 95% CrI –0.59 to –0.01) at preventing anxiety immediately post intervention. There was evidence that exercise was effective in preventing anxiety in targeted secondary school settings (SMD –0.47, 95% CrI –0.86 to –0.09). There was weak evidence that cognitive–behavioural interventions may prevent anxiety in universal (SMD –0.07, 95% CrI –0.23 to 0.05) and targeted (SMD –0.38, 95% CrI –0.84 to 0.07) primary school settings. There was weak evidence that cognitive–behavioural (SMD –0.04, 95% CrI –0.16 to 0.07) and cognitive–behavioural + interpersonal therapy (SMD –0.18, 95% CrI –0.46 to 0.08) may be effective in preventing depression in universal secondary school settings. Third-wave (SMD –0.35, 95% CrI –0.70 to 0.00) and cognitive–behavioural interventions (SMD –0.11, 95% CrI –0.28 to 0.05) incorporating a psychoeducation component may be effective at preventing depression immediately post intervention. There was no evidence of intervention effectiveness in targeted secondary, targeted primary or universal primary school settings post intervention. The results for university settings were unreliable because of inconsistency in the network meta-analysis. A narrative summary was reported for five conduct disorder prevention studies, all in primary school settings. None reported the primary outcome at the primary post-intervention time point. The economic evidence review reported heterogeneous findings from six studies. Taking the perspective of a single school budget and based on cognitive–behavioural therapy intervention costs in universal secondary school settings, the cost–consequence analysis estimated an intervention cost of £43 per student. Limitations: The emphasis on disorder-specific prevention excluded broader mental health interventions and restricted the number of eligible conduct disorder prevention studies. Restricting the study to interventions delivered in the educational setting may have limited the number of eligible university-level interventions. Conclusions: There was weak evidence of the effectiveness of school-based, disorder-specific prevention interventions, although effects were modest and the evidence not robust. Cognitive–behavioural therapy-based interventions may be more effective if they include a psychoeducation component. Future work: Future trials for prevention of anxiety and depression should evaluate cognitive–behavioural interventions with and without a psychoeducation component, and include mindfulness/relaxation or exercise comparators, with sufficient follow-up. Cost implications must be adequately measured. Study registration: This study is registered as PROSPERO CRD42016048184. Funding: This project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 9, No. 8. See the NIHR Journals Library website for further project information

Comparative efficacy and acceptability of antidepressants, psychological interventions, and their combination for depressive disorder in children and adolescents:protocol for a network meta-analysis

Introduction Depressive disorder is common in children and adolescents, with important consequences and serious impairments in terms of personal and social functioning. While both pharmacological and psychological interventions have been shown to be effective, there is still uncertainty about the balance between these and what treatment strategy should be preferred in clinical practice. Therefore, we aim to compare and rank in a network meta-analysis (NMA) the commonly used psychological, pharmacological and combined interventions for depressive disorder in children and adolescents. Methods and analysis We will update the literature search of two previous NMAs for the identification of trials of antidepressant and psychotherapy alone for depressive disorder in children and adolescents. For identification of trials of combination interventions, seven databases (PubMed, EMBASE, CENTRAL (Cochrane Central Register of Controlled Trials), Web of Science, PsycINFO, CINAHL, LiLACS) will be searched from date of inception. We will also search ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform and check relevant reports on the US Food and Drug Administration website for unpublished data. Building on our previous findings in the field, we will include any commonly prescribed oral antidepressants and any manualised or structured psychotherapies, as well as their combinations. Randomised controlled trials assessing any active intervention against active comparator or pill placebo/psychological controls in acute treatment for depressive disorder in children and adolescents will be included. The primary outcomes will be efficacy (mean change in depressive symptoms), and acceptability of treatment (dropout rate due to any cause). The secondary outcomes will be remission rate, tolerability of treatment (dropouts for adverse events), as well as suicide-related outcomes (suicidal behaviour or ideation). We will perform Bayesian NMAs for all relative outcome measures. Subgroup analyses and sensitivity analyses will be conducted to assess the robustness of the findings. Dissemination This NMA will provide the most up to date and clinically useful information about the comparative efficacy and acceptability of antidepressants, psychological intervention and their combination in the acute treatment of children and adolescents with depressive disorder. This is the newest NMA and therefore these results are very important in terms of evidence-based medicine. The results will be disseminated through peer-reviewed publication. Protocol registration PROSPERO CRD42015020841

Heterogeneity of quality of life in young people attending primary mental health services

AIMS: The utility of quality of life (QoL) as an outcome measure in youth-specific primary mental health care settings has yet to be determined. We aimed to determine: (i) whether heterogeneity on individual items of a QoL measure could be used to identify distinct groups of help-seeking young people; and (ii) the validity of these groups based on having clinically meaningful differences in demographic and clinical characteristics. METHODS: Young people, at their first presentation to one of five primary mental health services, completed a range of questionnaires, including the Assessment of Quality of Life–6 dimensions adolescent version (AQoL-6D). Latent class analysis (LCA) and multivariate multinomial logistic regression were used to define classes based on AQoL-6D and determine demographic and clinical characteristics associated with class membership. RESULTS: 1107 young people (12–25 years) participated. Four groups were identified: (i) no-to-mild impairment in QoL; (ii) moderate impairment across dimensions but especially mental health and coping; (iii) moderate impairment across dimensions but especially on the pain dimension; and (iv) poor QoL across all dimensions along with a greater likelihood of complex and severe clinical presentations. Differences between groups were observed with respect to demographic and clinical features. CONCLUSIONS: Adding multi-attribute utility instruments such as the AQoL-6D to routine data collection in mental health services might generate insights into the care needs of young people beyond reducing psychological distress and promoting symptom recovery. In young people with impairments across all QoL dimensions, the need for a holistic and personalised approach to treatment and recovery is heightened