NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE Centre for Clinical Practice Surveillance Programme

NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE Centre for Clinical Practice Surveillance Programme Clinical guideline CG28: Depression in children and young people: identification and management in primary, community and secondary care Publication date September 2005 Previous review dates 2 year review: 2007 (no update) 5 year review: 2010 (no update) Surveillance report for GE October 2013 Key findings Potential impact on guidance Evidence identified from evidence update Evidence identified from literature search Feedback from Guideline Development Group Anti-discrimination and equalities considerations No update Rapid update Standard update Transfer to static list No Change review cycle Surveillance recommendation GE is asked to consider the proposal to update the guideline as a rapid update (using Guideline Updates standing committee). GE are asked to note that this yes to update proposal will not be consulted on. CG28 Depression in children, Surveillance review decision, October 2013 1 of 20

NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE Centre for Clinical Practice Surveillance Programme Surveillance review of CG28: Depression in children and young people: identification and management in primary, community and secondary care Background information Guideline issue date: 2005 2 year review: 2007 (no update) 5 year review: 2010 (no update) 8 year review: 2013 NCC: Mental Health Recommendation for Guidance Executive Main s from previous surveillance review 1. CG28 was previously reviewed for update in 2007 and 2010. At both review points, no new evidence was identified which would change the direction of guideline recommendations. The review recommendations at both review points was that the guideline should not be considered for an update. Eight year surveillance review 2. The Evidence Update on CG28: Depression in children (published June 2013) was used as the primary source of evidence for this surveillance review which considered new evidence since the last surveillance review (searches conducted August 2010). An additional literature search for randomised controlled trials and systematic reviews was carried out between January 2013 (the end of the search CG28 Depression in children, Surveillance review decision, October 2013 2 of 20

period for the Evidence Update) and August 2013 and relevant abstracts were assessed. Clinical feedback on the guideline was obtained from six members of the GDG (including the Chair) through a discussion at the Evidence Update Advisory Group meeting in March 2013. 3. New evidence that may impact on recommendations was identified relating to two clinical areas within the guideline: Clinical area 1: Psychological interventions for mild depression recommendation 1.5.2.1 Q: For children and young people who are depressed, does a psychological intervention when compared to standard care / wait-list control/ protocol driven clinical management/ another psychological intervention produce benefits/ harms on the specified outcomes? Evidence summary GDG/clinical perspective Impact Evidence identified from Evidence Update Classroom-based CBT in young people at high risk of depression A study identified Evidence Update indicated that delivery of a group CBT programme in schools may not reduce symptoms of depression 1. In addition, the study could not rule out a potential small clinical harm from classroombased CBT compared with usual school provision. Computerised CBT for young people with depressive symptoms One trial was identified for the Evidence Update which compared an interactive fantasy game designed to deliver CBT for the treatment of depression with usual care (counselling) for young people (12-19 year olds) 2. The results of the study indicated that computerised CBT was not inferior to usual care in the primary, per protocol analysis, as shown difference in mean reduction in Children s Depression Rating No GDG feedback was provided for this clinical area. New evidence is available which suggests that computerised delivery of CBT may be feasible and beneficial in children and young people with mild depression. Furthermore, there is evidence that has been published since the guideline was released indicating that group CBT delivered in a school setting may not reduce the symptoms of depression. This new evidence may enable modification of the current guideline recommendation for CBT in children and young people with mild depression which indicates that group CBT is recommended (in addition to other psychological therapies) and could be provided by appropriately trained professionals in primary care, schools, social services and the voluntary sector or in tier 2 CAMHS. CG28 Depression in children, Surveillance review decision, October 2013 3 of 20

Scale (CDRS-R) score, whilst there was a significantly higher remission rate with the computerised intervention compared with usual care. The Evidence Update concluded that computerised CBT may be a valid treatment option for young people with mild depression. Evidence identified from literature search Computerised CBT for young people with depressive symptoms The feasibility, acceptability and efficacy of a computerised CBT programme compared with a computer-administered attention placebo program with psychoeducational content for depressed adolescents was evaluated in an RCT 3. Adolescents treated with computerised CBT showed greater symptom improvement on CDRS- R scale than those in the control group. Clinical area 2: Pharmacological interventions for moderate to severe depression recommendations 1.6.1.2 / 1.6.2.1-1.6.2.4 / 1.6.3.1-1.6.3.2 / 1.6.4.1 Q: For children and young people who are depressed, does any antidepressant when compared to any psychological intervention produce benefits/ harms on the specified outcomes? Q: For children and young people who are depressed, does the combination of an antidepressant and a psychological intervention when compared to an antidepressant alone/ psychological intervention alone produce benefits/ harms on the specified outcomes? Evidence summary GDG/clinical perspective Impact Evidence identified from Evidence Update Three systematic reviews of pharmacological interventions for depression in children and young people (including a Cochrane review) were Several GDG members were consulted at the Evidence Update Advisory Group meeting in March 2013 whereby it was felt that the recommendations in the 2005 Since publication of the guideline new evidence for moderate to severe depression in children and young people has been published which has been meta-analysed in the systematic reviews outlined CG28 Depression in children, Surveillance review decision, October 2013 4 of 20

identified for the Evidence Update which compared: Psychological vs. antidepressant therapy o One Cochrane review carried out an analysis of antidepressant vs. psychological therapy indicating that antidepressant therapy was more effective as measured by Clinician Defined Remission although suicide ideation was greater 4 Combined antidepressant plus psychological therapy vs. psychological therapy o The Cochrane review found no significant difference in remission rates, dropouts or suicide ideation between combination therapy vs. antidepressants for major depressive disorder 4 Combined antidepressant plus psychological therapy vs. antidepressant therapy o Two systematic reviews found no significant differences between combination or antidepressant therapy for the following outcomes: remission rates, dropouts or suicide ideation 4 and depressive symptoms, suicidality or global improvement 5 o One systematic review found significant improvement in the combination group using the Children s guideline relating to antidepressant treatment for moderate to severe depression were too conservative. During guideline development the GDG were concerned about suicide ideation following treatment but now the consensus among the literature is that it is safer to treat with antidepressants rather than wait. As such, the GDG felt that the cumulative evidence now supports more rapid utilisation of fluoxetine for moderate to severe depression (sooner than the 12 weeks currently recommended in the guideline). in this section. The results of these studies suggest that the recommendations on pharmacological treatment for moderate to severe depression may need to be revised as new data indicates there may be little difference in efficacy between monotherapy with psychological or antidepressant treatment for moderate or severe depression although suicide ideation may be greater following antidepressant treatment. Furthermore, the additional benefit of adding CBT to antidepressant therapy compared with antidepressants alone may not be as significant as previously thought whilst clinical feedback from the GDG suggests that the literature supports more rapid utilisation of fluoxetine for moderate to severe depression (sooner than the 12 weeks currently recommended). Additionally, since publication of CG28, fluoxetine has been licensed for use in children and young people aged 8 years and older to treat moderate to severe major depression that is unresponsive to psychological therapy after 4 6 sessions, in combination with a concurrent psychological therapy. Overall, the new identified evidence could have implications on the sequencing and timing of antidepressant treatment for moderate to severe depression currently recommended. CG28 Depression in children, Surveillance review decision, October 2013 5 of 20

Global Assessment Scale but no significant difference compared with antidepressants on the Clinical Global Impression Scale or CDRS-R scale for major depressive disorder 6 Ongoing research 4. The IMPACT trial is an RCT of short-term psychoanalytic psychotherapy, CBT and specialist clinical care for children and young people with depression. The results of this trial have not been published at this time (the study is expected to be completed by 2016) therefore it is not possible to determine any potential impact on guideline recommendations. However, data from this trial may contribute towards the evidence base relating to management of depression in children and young people in future surveillance reviews. Anti-discrimination and equalities considerations 5. None identified. Implications for other NICE programmes 6. This guideline relates to a Quality Standard on depression in children (expected to publish September 2013). 7. None of the quality statements are likely to be affected proposed areas for update. Conclusion 8. Through the review of CG28 new evidence which may potentially change the direction of guideline recommendations was identified in the following areas: a. Psychological interventions for mild depression b. Pharmacological interventions for moderate to severe depression 9. For all other areas of the guideline no evidence was identified which would impact on recommendations. CG28 Depression in children, Surveillance review decision, October 2013 6 of 20

Surveillance recommendation 10. GE is asked to consider the proposal to update the guideline as a rapid update (using Guideline Updates standing committee). GE are asked to note that this yes to update proposal will not be consulted on. Mark Baker Centre Director Sarah Willett Associate Director Emma McFarlane Technical Analyst Centre for Clinical Practice October 2013 CG28 Depression in children, Surveillance review decision, October 2013 7 of 20

References 1. Stallard P, Sayal K, Phillips R et al. (2012) Classroom based cognitive behavioural therapy in reducing symptoms of depression in high risk adolescents: pragmatic cluster randomised controlled trial. BMJ 345:e6058. 2. Merry SN, Stasiak K, Shepherd M et al. (2012) The effectiveness of SPARX, a computerised self help intervention for adolescents seeking help for depression: randomised controlled non-inferiority trial. BMJ 344:e2598. 3. Stasiak K, Hatcher S, Frampton C et al. (20-12-2012) A Pilot Double Blind Randomized Placebo Controlled Trial of a Prototype Computer- Based Cognitive Behavioural Therapy Program for Adolescents with Symptoms of Depression. Behav.Cogn.Psychother. 1-17. 4. Cox GR, Callahan P, Churchill R et al. (2012) Psychological therapies versus antidepressant medication, alone and in combination for depression in children and adolescents. Cochrane Database Syst.Rev. 11:CD008324. 5. Dubicka B, Elvins R, Roberts C et al. (2010) Combined treatment with cognitive-behavioural therapy in adolescent depression: metaanalysis. Br.J Psychiatry 197:433-440. 6. Calati R, Pedrini L, and Alighieri S. (2011) Is cognitive behavioural therapy an effective complement to antidepressants in adolescents? A meta-analysis. Acta Neuropsychiatrica 23:263-271. CG28 Depression in children, Surveillance review decision, October 2013 8 of 20

Appendix 1 Decision matrix Surveillance and identification of triggers for updating CG28. The table below provides summaries of the evidence for key questions for which studies were identified. Conclusions from previous Do screening instruments for depression have an influence on detection of depression in children and young people? Through a focused search 34 studies relevant to the clinical question were identified. Studies focused on the diagnostic accuracy, reliability and validity of depression screening instruments and interview-based instruments. However, due to the heterogeneous nature of the studies, it was concluded that further research is necessary to confirm reliability, validity and clinical utility of screening instruments in children and young people. No: new evidence (two studies identified through literature search) supports current recommendations which state that healthcare professionals in primary care settings should be familiar with screening for mood disorders and should have regular access to specialist supervision and consultation. New evidence is consistent with guideline recommendations. How might services be organised to detect depression in children and young people? No No relevant evidence identified. What risk factors are associated with depression in children and young people? One study was identified through the high-level search which concluded that cognitive and familial factors predict No: risk factors (three studies identified through literature search) identified included female sex, poor inter-parental or adolescent-parent New evidence is consistent with guideline recommendations. CG28 Depression in children, Surveillance review decision, October 2013 9 of 20

those depressed youth who have high relationship, low socio-economic status, parental levels of hopelessness. This study was depression, low level of parental education and judged as not likely to impact on poor academic performance. These risk factors guideline recommendations. are broadly in line with those discussed in the guideline. For children and young people who are depressed, does any antidepressant when compared to placebo/ comparator drug, produce benefits/ harms on the specified outcomes? A meta-analysis, two systematic reviews and 9 RCTs were identified through the focused search. The reviews focusing on fluoxetine indicated that this drug is effective in reducing depression symptoms in both children and adolescents. The efficacy and safety of tricyclic antidepressants was unclear. The RCTs included escitalopram, atomexetine and venlafaxine which were not licensed for use in children in 2010. The Evidence Update highlighted that since publication of CG28, fluoxetine has been licensed for use in children and young people aged 8 years and older to treat moderate to severe major depression that is unresponsive to psychological therapy after 4 6 sessions, only in combination with a concurrent psychological therapy. In addition, at June 2013, citalopram, escitalopram, mirtazapine, paroxetine, sertraline and venlafaxine did not have UK marketing authorisation for use in depression in children and young people under the age of 18 years, and it is stated ir summary of product characteristics that they are either not recommended, or should not be used, for this indication. This was also the case at the time of guideline publication. Three tricyclic antidepressants are licensed for Generally new evidence is consistent with guideline recommendations. The extension of the fluoxetine license has been taken into consideration below. CG28 Depression in children, Surveillance review decision, October 2013 10 of 20

use in children over 12 years with depressive illness (doxepin, nortryptyline, trimipramine) however, evidence of effectiveness of these drugs in children and adolescents with depression remains unclear. For children and young people who are depressed, does any drug treatment (other than antidepressants) when compared to placebo/ comparator drug, produce benefits/ harms on the specified outcomes? No No relevant evidence identified. For children and young people who are depressed, does any antidepressant when compared to any psychological intervention produce benefits/ harms on the specified outcomes? For children and young people who are depressed, does the combination of an antidepressant and a psychological intervention when compared to an antidepressant alone/ psychological intervention alone produce benefits/ harms on the specified outcomes? The following trials were identified: TORDIA, TADS, ADAPT and TASA, a meta-analysis of these trials plus data from two older studies. No At this review point it was concluded that due to the small number of studies included in the analysis and the heterogeneity between studies (including variations in methodology), the generalisability of the results was limited. Evidence update Three systematic reviews (including a Cochrane review) are discussed in the Evidence Update which compare: Psychological vs. antidepressant o Cox 2012 - An analysis of antidepressant vs. psychological treatment indicated antidepressant therapy was more effective as measured by Clinician Defined Remission although suicide ideation Following consideration of the identified meta-analyses, the Evidence Update concluded that there may be little difference in efficacy between monotherapy with psychological or antidepressant treatment for moderate or severe depression in the populations of young people studied (although there was some evidence to suggest a greater effect with antidepressant monotherapy as measured by clinician-defined remission). There is an increased risk of suicidal ideation from antidepressant monotherapy CG28 Depression in children, Surveillance review decision, October 2013 11 of 20

was greater Combination vs. antidepressant o Cox 2012 - found no significant difference in remission rates, dropouts or suicide ideation between combination therapy vs. antidepressants for major depressive disorder o Dubika 2010 no significant benefit of combination vs. antidepressant alone for depressive symptoms, suicidality and global improvement after acute treatment or at follow-up o Calati 2011 - found significant improvement in the combination group using the CGAS scale but no significant difference compared with antidepressants on the CGI-I or CDRS-R scale for major depressive disorder Combination vs. psychological o Cox 2012 - found no significant difference in remission rates, dropouts or suicide ideation between combination therapy vs. antidepressants for major compared with psychological treatment alone. Combining CBT with antidepressants may be beneficial with regard to some measures of global functioning, although benefits in other measures are less clear. Combining CBT with antidepressants has not been convincingly shown to mitigate the risk of suicidal ideation from antidepressants. One RCT was included in the guideline which evaluated combination therapy (fluoxetine + CBT) vs. fluoxetine / fluoxetine + CBT vs. CBT and fluoxetine vs. CBT. The guideline currently recommends that children and young people with moderate to severe depression should be offered psychological therapy first-line. If there is no response after 3 months, an alternative psychological therapy or addition of antidepressant should be considered. Antidepressant treatment should only be given in combination with a psychological therapy* (recommendations 1.6.1.2 / 1.6.2.1-1.6.2.4 / 1.6.3.1-1.6.3.2 / 1.6.4.1). CG28 Depression in children, Surveillance review decision, October 2013 12 of 20

depressive disorder Calati R, Pedrini L, Alighieri S et al. (2011) Is cognitive behavioural therapy an effective complement to antidepressants in adolescents? A meta-analysis. Acta Neuropsychiatrica 23: 263 71 Cox GR, Callahan P, Churchill R et al. (2012) Psychological therapies versus antidepressant medication, alone and in combination for depression in children and adolescents. Cochrane Database of Systematic Reviews issue 11: CD008324 Dubicka B, Elvins R, Roberts C et al. (2010) Combined treatment with cognitive-behavioural therapy in adolescent depression: metaanalysis. British Journal of Psychiatry 197: 433 40 Finally, studies were identified through the literature search which would not impact on guideline recommendations: Vitamin C as an adjuvant to fluoxetine (one RCT) Tricyclic drugs for depression in children and young people (one Cochrane review and Since publication of the guideline new evidence for major depressive disorder has been published in the TORDIA, TADS and ADAPT trials (and others) which has been meta-analysed in several systematic reviews. The results of these studies suggest that recommendations on pharmacological treatment for moderate to severe depression may need to be revised as new data indicates there may be little difference in efficacy between monotherapy with psychological or antidepressant treatment for moderate or severe depression although suicide ideation may be greater. Furthermore, the additional benefit of adding to CBT to antidepressant therapy compared with antidepressants alone may not be as significant as previously thought. Several GDG members were consulted at the Evidence Update Advisory Group meeting and, at that time, it was felt that the recommendations in the 2005 guideline relating to antidepressant treatment for moderate to severe depression were too conservative. At the time the GDG were concerned about CG28 Depression in children, Surveillance review decision, October 2013 13 of 20

one meta-analysis) Antidepressant-associated mood switching and mood elevation (two systematic reviews) Association between parent-child conflict and treatment outcomes (one RCT) Prevalence of subthreshold depression (two systematic reviews) suicide ideation following treatment but now the consensus among the literature is that it is safer to treat with antidepressants rather than wait. As such, the GDG feel that the cumulative evidence now supports more rapid utilisation of fluoxetine for moderate to severe depression (sooner than the 12 weeks currently recommended). *See note above under Q on antidepressant vs. placebo / antidepressant regarding drug licensing. For children and young people with psychotic depression, does any pharmacological intervention produce benefits/ harms on the specified outcomes? No No relevant evidence identified. For children and young people who are depressed, does an intervention other than psychological or pharmacological interventions produce benefits/ harms on the specified outcomes? No: one systematic review was identified through the literature search which investigated the efficacy of electroconvulsive therapy and the potential risks and complications of the procedure in depressed adolescents. No specific data was reported in the abstract therefore, it is not clear whether the results of this review would impact on the recommendations on electroconvulsive therapy. New evidence is unlikely to impact on current recommendations. CG28 Depression in children, Surveillance review decision, October 2013 14 of 20

For children and young people who are depressed, does a psychological intervention when compared to standard care / wait-list control/ protocol driven clinical management/ another psychological intervention produce benefits/ harms on the specified outcomes? Through the focused search 36 studies relevant to the clinical question were identified. Literature was identified evaluating self-help therapies, individual therapies (including cognitive behavioural therapy (CBT) and interpersonal therapy), group CBT and family therapies. The following areas were of particular relevance but it was felt that further research was required: No Evidence update One trial was identified for the Evidence Update which compared SPARX (Smart, Positive, Active, Realistic, X-factor thoughts) an interactive fantasy game designed to deliver CBT for the treatment of clinically significant depression with usual care (counselling) for young people (12-19 year olds). The results of the study indicated that SPARX was not inferior The Evidence Update concluded that computerised CBT may be a valid treatment option for young people with mild depression. A systematic review identified at the 5 year review point and a pilot RCT identified through the literature search conducted for the review of CG90 (study not identified by EU or surveillance search) also reported feasibility and efficacy of computerised CBT. CBT in schools One RCT results varied between schools / one systematic review schoolbased CBT had positive effect to usual care in the primary, per protocol analysis (participants completing at least 4 of the SPARX modules). However, there was a significantly higher remission rate (score less than 30 on the CDRS-R) with SPARX than usual care. Computerised CBT - One systematic review - all included studies reported reductions in clinical symptoms although satisfaction with treatment was moderate to high from both children and parents - high levels of drop out and non-completion reported Merry SN, Stasiak K, Shepherd M et al. (2012) The effectiveness of SPARX, a computerised self help intervention for adolescents seeking help for depression: a randomised controlled non-inferiority trial. British Medical Journal 344: e2598. In terms of group CBT for mild depression, one In terms of delivery of CBT in schools, the evidence based is mixed with a systematic review and RCT from the 2005 review indicating positive and variable effects respectively whilst a study discussed in the Evidence Update suggesting that delivery of a group CBT programme in schools may not reduce symptoms of depression. No relevant studies were identified through the literature search conducted between Jan Aug 2013. Taken together, new evidence is available which suggests that computerised delivery of CBT may be beneficial in children and CG28 Depression in children, Surveillance review decision, October 2013 15 of 20

RCT was identified which indicated that a group CBT programme delivered universally in a school setting, may not reduce symptoms of depression in young people at high risk of depression, and could increase reporting of symptoms. Stallard P, Sayal K, Phillips R et al. (2012) Classroom based cognitive behavioural therapy in reducing symptoms of depression in high risk adolescents: pragmatic cluster randomised controlled trial. British Medical Journal 345: e6058. Literature search The feasibility, acceptability and efficacy of a computerised cognitive behavioural therapy (ccbt) program compared with a computeradministered attention placebo program with psychoeducational content for depressed adolescents was evaluated in an RCT. Adolescents treated with ccbt showed greater symptom improvement on CDRS-R than those in the control group. Stasiak K, Hatcher S, Frampton C, Merry SN (2012). A Pilot Double Blind Randomized Placebo Controlled Trial of a Prototype young people with mild depression. Furthermore, there is evidence that has been published since the guideline was released indicating that group CBT delivered in a school setting may not reduce the symptoms of depression. This new evidence may enable modification of the current guideline recommendation for CBT in children and young people with mild depression: Mild depression (Recommendation 1.5.2.1): o Individual non-directive supportive therapy, group CBT or guided self-help for a limited period (approximately 2 to 3 months). This could be provided by appropriately trained professionals in primary care, schools, social services and the voluntary sector or in tier 2 CAMHS N.B. The Evidence Update suggested that other studies on computerised CBT are available which were published prior to the search date of the Evidence Update but these studies were not prioritised and were not discussed specifically. CG28 Depression in children, Surveillance review decision, October 2013 16 of 20

Computer-Based Cognitive Behavioural Therapy Program for Adolescents with Symptoms of Depression. Behavioural and Cognitive Psychotherapy [Dec 20: 1-17 Epub ahead of print] Finally, studies were identified through the literature search on the following psychological interventions but the results of these studies currently would not impact guideline recommendations: Attachment based family therapy (one study) Feasibility of delivering school-based prevention programme (one systematic review) Short-term psychodynamic psychotherapy (one meta-analysis) Multifamily psychoeducational psychotherapy (one RCT) Behavioural intervention (one RCT) Parent-child interaction therapy (one systematic review) CBT (three RCTs) Primary care provider engagement (one RCT) For a psychological intervention that works, are [outcomes] correlated with any characteristics of the therapist/ service user? CG28 Depression in children, Surveillance review decision, October 2013 17 of 20

No: one RCT focusing on a modular approach to therapy was reported in the Evidence Update but it was concluded that further research in a UK or European setting is required before considering whether there would be an impact on the guideline. New evidence is unlikely to impact on guideline recommendations. For children and young people who are undiagnosed but at high risk of depression, does self-help or other psychological interventions when compared to standard care alone, produce benefits/ harms on the specified outcomes? Several studies, including RCTs and systematic reviews, focused on selfhelp therapies for depression. Most studies evaluated internet-based therapies. The results of the studies were considered unlikely to impact on guideline recommendations. No: additional studies on internet-based selfhelp interventions were identified. Although the use of the internet is not specifically included in the recommendations, Appendix K of the guideline (common forms of self-help) describes the use of the internet for self-help interventions. New evidence is unlikely to impact on current recommendations. For children and young people who are undiagnosed but at high risk of depression, does family support/ parental education when compared to standard care, produce benefits/ harms on the specified outcomes? Three studies were identified through the high-level search which assessed family therapy and family support in children and young people at high-risk of depression. The results of the studies supported guideline recommendations. No No relevant evidence identified. For children and young people who are depressed, does self-help when compared to standard care, produce benefits/ harms on the specified outcomes? Studies on exercise (one study) and relaxation (one study) were identified. No: one small study was identified through the literature search which demonstrated a small New evidence is consistent with guideline recommendations. CG28 Depression in children, Surveillance review decision, October 2013 18 of 20

The results of the studies were significant effect of physical activity on considered unlikely to impact on depression which supports the current guideline recommendations. recommendation which states that advice should be given on the benefits of regular exercise. For children and young people who are depressed, does family support/ parental education when compared to standard care, produce benefits/ harms on the specified outcomes? No: a post-hoc analysis was identified Evidence Update which concluded that a range of individual characteristics and family contextual issues may moderate the effects of treatment, consistent with CG28. New evidence is consistent with guideline recommendations. For children and young people who are depressed, is there any subgroup for which inpatient treatment produces benefits on the specified outcomes? No No relevant evidence identified. For children and young people who are depressed, is there any subgroup in which social/ environmental treatments alone produce benefits on the specified outcomes? (e.g., in young people who are experiencing bullying or abuse)? No No relevant evidence identified. For children and young people who are depressed, do antidepressant drugs, when compared to standard care, prevent relapse in the long term when prescribed in the recommended maintenance dose range? No No relevant evidence identified. For children and young people who are depressed, how long should antidepressant drug treatment be continued for prevention of relapse? No No relevant evidence identified. For children and young people who are depressed, do psychological interventions, when compared to standard care, prevent relapse in the long term? No No relevant evidence identified. CG28 Depression in children, Surveillance review decision, October 2013 19 of 20

What are the key elements of care, particularly service organisations and interfaces between services, to maximise patient's outcomes? No No relevant evidence identified. CG28 Depression in children, Surveillance review decision, October 2013 20 of 20