Bernadka Dubicka

Selective serotonin reuptake inhibitors (SSRIs) and routine specialist care with and without cognitive behaviour therapy in adolescents with major depression: randomised controlled trial

Objective To determine whether a combination of a selective serotonin reuptake inhibitor (SSRIs) and cognitive behaviour therapy (CBT) together with clinical care is more effective in the short term than an SSRI and clinical care alone in adolescents with moderate to severe major depression. Design Pragmatic randomised controlled superiority trial. Setting 6 outpatient clinics in Manchester and Cambridge. Participants 208 adolescents, aged 11-17, with moderate to severe major or probable major depression who had not responded to a brief initial intervention. Adolescents with suicidality, depressive psychosis, or conduct disorder were included. Interventions 103 adolescents received an SSRI and routine care; 105 received an SSRI, routine care, and CBT. The trial lasted 12 weeks, followed by a 16 week maintenance phase. Main outcome measures Change in score on the Health of the Nation outcome scales for children and adolescents (primary outcome) from baseline with 12 weeks as the primary and 28 weeks as the follow-up end point. Secondary measures were change in scores on the mood and feelings questionnaire, the revised childrens depression rating scale, the childrens global assessment scale, and the clinical global impression improvement scale. Results At 12 weeks the treatment effect for the primary outcome was −0.64 (95% confidence interval −2.54 to 1.26, P=0.50). In a longitudinal analysis, there was no difference in effectiveness of treatment for the primary (average treatment effect 0.001, −1.52 to 1.52, P=0.99) or secondary outcome measures. On average there was a decrease in suicidal thoughts and self harm. There was no evidence of a protective effect of cognitive behaviour therapy on suicidal thinking or action. By 28 weeks, 57% were much or very much improved with 20% remaining unimproved. Conclusions For adolescents with moderate to severe major depression there is no evidence that the combination of CBT plus an SSRI in the presence of routine clinical care contributes to an improved outcome by 28 weeks compared with the provision of routine clinical care plus an SSRI alone. Trial registration Current Controlled Trials ISRCNT 83809224.

Combined treatment with cognitive–behavioural therapy in adolescent depression: meta-analysis

BACKGROUND The treatment of adolescent depression is controversial and studies of combined treatment (antidepressants and cognitive-behavioural therapy, CBT) have produced conflicting findings. AIMS To address the question of whether CBT confers additional benefit to antidepressant treatment in adolescents with unipolar depression for depressive symptoms, suicidality, impairment and global improvement. METHOD Meta-analysis of randomised controlled trials (RCTs) of newer-generation antidepressants and CBT in adolescent depression. RESULTS There was no evidence of a statistically significant benefit of combined treatment over antidepressants for depressive symptoms, suicidality and global improvement after acute treatment or at follow-up. There was a statistically significant advantage of combined treatment for impairment in the short-term (at 12 weeks) only. There was some evidence of heterogeneity between studies. CONCLUSIONS Adding CBT to antidepressants confers limited advantage for the treatment of an episode of depression in adolescents. The variation in sampling and methodology between studies, as well as the small number of trials, limits the generalisability of the findings and any conclusions that can be drawn. Future studies should examine predictors of response to treatment as well as clinical components that may affect outcome.

Improving mood with psychoanalytic and cognitive therapies (IMPACT): a pragmatic effectiveness superiority trial to investigate whether specialised psychological treatment reduces the risk for relapse in adolescents with moderate to severe unipolar depression: study protocol for a randomised controlled trial

BackgroundUp to 70% of adolescents with moderate to severe unipolar major depression respond to psychological treatment plus Fluoxetine (20-50 mg) with symptom reduction and improved social function reported by 24 weeks after beginning treatment. Around 20% of non responders appear treatment resistant and 30% of responders relapse within 2 years. The specific efficacy of different psychological therapies and the moderators and mediators that influence risk for relapse are unclear. The cost-effectiveness and safety of psychological treatments remain poorly evaluated.Methods/DesignImproving Mood with Psychoanalytic and Cognitive Therapies, the IMPACT Study, will determine whether Cognitive Behavioural Therapy or Short Term Psychoanalytic Therapy is superior in reducing relapse compared with Specialist Clinical Care. The study is a multicentre pragmatic effectiveness superiority randomised clinical trial: Cognitive Behavioural Therapy consists of 20 sessions over 30 weeks, Short Term Psychoanalytic Psychotherapy 30 sessions over 30 weeks and Specialist Clinical Care 12 sessions over 20 weeks. We will recruit 540 patients with 180 randomised to each arm. Patients will be reassessed at 6, 12, 36, 52 and 86 weeks. Methodological aspects of the study are systematic recruitment, explicit inclusion criteria, reliability checks of assessments with control for rater shift, research assessors independent of treatment team and blind to randomization, analysis by intention to treat, data management using remote data entry, measures of quality assurance, advanced statistical analysis, manualised treatment protocols, checks of adherence and competence of therapists and assessment of cost-effectiveness. We will also determine whether time to recovery and/or relapse are moderated by variations in brain structure and function and selected genetic and hormone biomarkers taken at entry.DiscussionThe objective of this clinical trial is to determine whether there are specific effects of specialist psychotherapy that reduce relapse in unipolar major depression in adolescents and thereby costs of treatment to society. We also anticipate being able to utilise psychotherapy experience, neuroimaging, genetic and hormone measures to reveal what techniques and their protocols may work best for which patients.Trial RegistrationCurrent Controlled Trials ISRCTN83033550

Treated depression in adolescents: predictors of outcome at 28 weeks

BACKGROUND There is great heterogeneity of clinical presentation and outcome in paediatric depression. AIMS To identify which clinical and environmental risk factors at baseline and during treatment predicted major depression at 28-week follow-up in a sample of adolescents with depression. METHOD One hundred and ninety-two British adolescents with unipolar major depression were enrolled in a randomised controlled trial (the Adolescent Depression Antidepressants and Psychotherapy Trial, ADAPT). Participants were treated for 28 weeks with routine psychosocial care and selective serotonin reuptake inhibitors (SSRIs), with half also receiving cognitive-behavioural therapy (CBT). Full clinical and demographic assessment was carried out at baseline and 28 weeks. RESULTS Depression at 28 weeks was predicted by the additive effects of severity, obsessive-compulsive disorder and suicidal ideation at entry together with presence of at least one disappointing life event over the follow-up period. CONCLUSIONS Clinicians should assess for severity, suicidality and comorbid obsessive-compulsive disorder at presentation and should monitor closely for subsequent life events during treatment.

Cognitive behavioural therapy and short-term psychoanalytical psychotherapy versus a brief psychosocial intervention in adolescents with unipolar major depressive disorder (IMPACT): a multicentre, pragmatic, observer-blind, randomised controlled superiority trial

Summary Background Psychological treatments for adolescents with unipolar major depressive disorder are associated with diagnostic remission within 28 weeks in 65–70% of patients. We aimed to assess the medium-term effects and costs of psychological therapies on maintenance of reduced depression symptoms 12 months after treatment. Methods We did this multicentre, pragmatic, observer-blind, randomised controlled superiority trial (IMPACT) at 15 National Health Service child and adolescent mental health service (CAMHS) clinics in three regions in England. Adolescent patients (aged 11–17 years) with a diagnosis of DSM IV major depressive disorder were randomly assigned (1:1:1), via a web-based randomisation service, to receive cognitive behavioural therapy (CBT) or short-term psychoanalytical therapy versus a reference brief psychological intervention. Randomisation was stochastically minimised by age, sex, self-reported depression sum score, and region. Patients and clinicians were aware of group allocation, but allocation was concealed from outcome assessors. Patients were followed up and reassessed at weeks 6, 12, 36, 52, and 86 post-randomisation. The primary outcome was self-reported depression symptoms at weeks 36, 52, and 86, as measured with the self-reported Mood and Feelings Questionnaire (MFQ). Because our aim was to compare the two psychological therapies with the brief psychosocial intervention, we first established whether CBT was inferior to short-term psychoanalytical psychotherapy for the same outcome. Primary analysis was by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN83033550. Findings Between June 29, 2010, and Jan 17, 2013, we randomly assigned 470 patients to receive the brief psychosocial intervention (n=158), CBT (n=155), or short-term psychoanalytical therapy (n=157); 465 patients comprised the intention-to-treat population. 392 (84%) patients had available data for primary analysis by the end of follow-up. Treatment fidelity and differentiation were established between the three interventions. The median number of treatment sessions differed significantly between patients in the brief psychosocial intervention group (n=6 [IQR 4–11]), CBT group (n=9 [5–14]), and short-term psychoanalytical therapy group (n=11 [5–23]; p<0·0001), but there was no difference between groups in the average duration of treatment (27·5 [SD 21·5], 24·9 [17·7], 27·9 [16·8] weeks, respectively; Kruskal–Wallis p=0·238). Self-reported depression symptoms did not differ significantly between patients given CBT and those given short-term psychoanalytical therapy at weeks 36 (treatment effect 0·179, 95% CI −3·731 to 4·088; p=0·929), 52 (0·307, −3·161 to 3·774; p=0·862), or 86 (0·578, −2·948 to 4·104; p=0·748). These two psychological treatments had no superiority effect compared with brief psychosocial intervention at weeks 36 (treatment effect −3·234, 95% CI −6·611 to 0·143; p=0·061), 52 (−2·806, −5·790 to 0·177; p=0·065), or 86 (−1·898, −4·922 to 1·126; p=0·219). Physical adverse events (self-reported breathing problems, sleep disturbances, drowsiness or tiredness, nausea, sweating, and being restless or overactive) did not differ between the groups. Total costs of the trial interventions did not differ significantly between treatment groups. Interpretation We found no evidence for the superiority of CBT or short-term psychoanalytical therapy compared with a brief psychosocial intervention in maintenance of reduced depression symptoms 12 months after treatment. Short-term psychoanalytical therapy was as effective as CBT and, together with brief psychosocial intervention, offers additional patient choice for psychological therapy, alongside CBT, for adolescents with moderate to severe depression who are attending routine specialist CAMHS clinics. Funding National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme, and the Department of Health.

Forum: the use of selective serotonin reuptake inhibitors in depressed children and adolescents: commentary on the meta-analysis by Hetrick et al.

Introduction In this meta-analysis of the use of selective serotonin reuptake inhibitors (SSRIs) in depressed children and adolescents, Hetrick et al. (in this issue) conclude that there is a modest place for the use of SSRIs in more severe depressions in adolescents and in subgroups that are yet to be well defined. Examining the role of these medications using meta-analytic techniques has been popular in recent years invariably from a rather negative perspective and without reference to the relative potency of treatments (pharmacological and psychological) available for these serious and potentially chronic mental disorders. This risks an unbalanced perspective of the efficacy of SSRIs, their clinical effectiveness and their pragmatic utility.

Adolescent depression: an evidence-based approach to intervention

Purpose of review There has been much recent research on the treatment and prevention of depression in young people. This paper reviews the results of this research. Recent findings Randomized trials support the use of both psychological and pharmacological treatments for established depressive disorder. Several studies have found that serotonin-specific reuptake inhibitors are an effective treatment for major depression in adolescents. Psychological treatments are now being evaluated in challenging samples, such as those with conduct disorder or those who repeatedly harm themselves. Evidence is accumulating too about how depression can be prevented. Summary Although much more work needs to be done, there are now several evidence-based options for treating depressed adolescents.

Associations between adolescent depression and parental mental health, before and after treatment of adolescent depression

The negative impacts of parental mental health problems on children and adolescents are well known, but the relationship between a child’s depression and their parents’ health is not so well understood. Being a carer/parent of someone with mental illness can be associated with negative outcomes for the caregiver. This paper reports the associations between the mental health of adolescents with major depression and their parents, before and after treatment of the adolescent’s depression. Data were collected as part of the Adolescent Depression Antidepressants and Psychotherapy Trial, a randomised controlled trial of selective serotonin reuptake inhibitors with and without cognitive behaviour therapy in 208 clinic-recruited adolescents with major depression. The baseline severity of depression in the adolescent was significantly associated with both maternal and paternal mental health (as rated by the General Health Questionnaire). This effect was not confounded by other psychiatric symptoms. The degree of improvement in parental and child mental health was positively correlated across time. Our results support the hypothesis that there is a significant association between parental mental health and adolescent depressive symptoms. This study was not able to establish the direction of this association. In clinical practice, the findings demonstrate the importance of considering the mental health of the parents when treating depressed adolescents.

Evidence-based treatment of adolescent major depression

Adolescent depression is a serious and debilitating disorder (see box). Up to one in 20 adolescents suffer from major depression at any point in time, and 20% of adolescents have at least one episode of clinical depression by the age of 18. Once depression is established it often becomes chronic. About a fifth of adolescents with major depression will continue to have a persistent disorder, and another third will recover but go on to have recurrent episodes. Depression runs in families and children of depressed parents have an increased risk of becoming depressed, which is likely to be due to both the direct effect of genes as well as the adverse influence of depressed parenting. Recent research has highlighted the complex interaction of genetic and environmental influences, such as adverse life events, in depression. #### The six Cs of depression Pure depression is rare, and it is usually accompanied by other psychiatric disorders. A recent UK study found that 89% of cases had a comorbid disorder and the average number of additional disorders was three.1 Other complications include school refusal, academic failure, impaired peer relations, drug and alcohol abuse, and family relationship problems. However, the most important complication is suicide and depression is the most important risk factor for suicidality. Findings from 20-year follow-up data of depressed children and adolescents have shown that 2.5% had committed suicide and nearly half had attempted suicide. Any treatment plan for adolescent depression therefore needs to take account of the chronic, relapsing nature of the disorder, consider aetiological factors such as parental depression, and address any concurrent psychiatric disorder and psychosocial complications, particularly suicidality. Early studies of cognitive behavioural therapy (CBT) were promising in the prevention and treatment of depression and meta-analyses found large effect sizes. However, a recent meta-analysis, which …

Cognitive-behavioural therapy and short-term psychoanalytic psychotherapy versus brief psychosocial intervention in adolescents with unipolar major depression (IMPACT): A multicentre, pragmatic, observer-blind, randomised controlled trial

BACKGROUND Although there are effective psychological treatments for unipolar major depression in adolescents, whether or not one or more of the available therapies maintain reduced depressive symptoms 1 year after the end of treatment is not known. This is a non-trivial issue because maintaining lowered depressive symptoms below a clinical threshold level reduces the risk for diagnostic relapse into the adult years. OBJECTIVE To determine whether or not either of two specialist psychological treatments, cognitive-behavioural therapy (CBT) or short-term psychoanalytic psychotherapy (STPP), is more effective than a reference brief psychosocial intervention (BPI) in maintaining reduction of depression symptoms in the year after treatment. DESIGN Observer-blind, parallel-group, pragmatic superiority randomised controlled trial. SETTING A total of 15 outpatient NHS clinics in the UK from East Anglia, north-west England and North London. PARTICIPANTS Adolescents aged 11-17 years with Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition major depression including those with suicidality, depressive psychosis and conduct disorder. Patients were randomised using stochastic minimisation controlling for age, sex and self-reported depression sum score; 470 patients were randomised and 465 were included in the analyses. INTERVENTIONS In total, 154 adolescents received CBT, 156 received STPP and 155 received BPI. The trial lasted 86 weeks and study treatments were delivered in the first 36 weeks, with 52 weeks of follow-up. MAIN OUTCOME MEASURES Mean sum score on self-reported depressive symptoms (primary outcome) at final study assessment (nominally 86 weeks, at least 52 weeks after end of treatment). Secondary measures were change in mean sum scores on self-reported anxiety symptoms and researcher-rated Health of the Nation scales for children and adolescents measuring psychosocial function. Following baseline assessment, there were a further five planned follow-up reassessments at nominal time points of 6, 12, 52 and 86 weeks post randomisation. RESULTS There were non-inferiority effects of CBT compared with STPP [treatment effect by final follow-up = -0.578, 95% confidence interval (CI) -2.948 to 4.104; p = 0.748]. There were no superiority effects for the two specialist treatments (CBT + STPP) compared with BPI (treatment effect by final follow-up = -1.898, 95% CI -4.922 to 1.126; p = 0.219). At final assessment there was no significant difference in the mean depressive symptom score between treatment groups. There was an average 49-52% reduction in depression symptoms by the end of the study. There were no differences in total costs or quality-of-life scores between treatment groups and prescribing a selective serotonin reuptake inhibitor (SSRI) during treatment or follow-up did not differ between the therapy arms and, therefore, did not mediate the outcome. CONCLUSIONS The three psychological treatments differed markedly in theoretical and clinical approach and are associated with a similar degree of clinical improvement, cost-effectiveness and subsequent maintenance of lowered depressive symptoms. Both STPP and BPI offer an additional patient treatment choice, alongside CBT, for depressed adolescents attending specialist Child and Adolescent Mental Health Services. Further research should focus on psychological mechanisms that are associated with treatment response, the maintenance of positive effects, determinants of non-response and whether or not brief psychotherapies are of use in primary care and community settings. LIMITATIONS Neither reason for SSRI prescribing or monitoring of medication compliance was controlled for over the course of the study, and the economic results were limited by missing data. TRIAL REGISTRATION Current Controlled Trials ISRCTN83033550. FUNDING This project was funded by the National Institute for Heath Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 12. See the National Institute for Heath Research Journals Library website for further project information. Funding was also provided by the Department of Health. The funders had no role in the study design, patient recruitment, data collection, analysis or writing of the study, any aspect pertinent to the study or the decision to submit to The Lancet.