Hiran Thabrew, Karolina Stasiak, Sarah E Hetrick, Stephen Wong, Jessica H Huss, Sally N Merry

Long-term physical conditions affect 10% to 12% of children and adolescents worldwide; these individuals are at greater risk of developing psychological problems, particularly anxiety and depression. Access to face-to-face treatment for such problems is often limited, and available interventions usually have not been tested with this population. As technology improves, e-health interventions (delivered via digital means, such as computers and smart phones and ranging from simple text-based programmes through to multimedia and interactive programmes, serious games, virtual reality and biofeedback programmes) offer a potential solution to address the psychological needs of this group of young people. To assess the effectiveness of e-health interventions in comparison with attention placebos, psychological placebos, treatment as usual, waiting-list controls, or non-psychological treatments for treating anxiety and depression in children and adolescents with long-term physical conditions. We searched the Cochrane Common Mental Disorders Group's Controlled Trials Register (CCMDTR to May 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 8, 2017), Web of Science (1900 - 18 August 2016, updated 31 August 2017) and Ovid MEDLINE, Embase, PsycINFO (cross-search 2016 to 18 Aug 2017). We hand-searched relevant conference proceedings, reference lists of included articles, and the grey literature to May 2016. We also searched international trial registries to identify unpublished or ongoing trials. We included randomised controlled trials (RCTs), cluster-randomised trials, and cross-over trials of e-health interventions for treating any type of long-term physical condition in children and adolescents (aged 0 to 18 years), and that measured changes in symptoms or diagnoses of anxiety, depression, or subthreshold depression. We defined long-term physical conditions as those that were more than three-months' duration. We assessed symptoms of anxiety and depression using patient- or clinician-administered validated rating scales based on DSM III, IV or 5 (American Psychological Association 2013), or ICD 9 or 10 criteria (World Health Organization 1992). Formal depressive and anxiety disorders were diagnosed using structured clinical interviews. Attention placebo, treatment as usual, waiting list, psychological placebo, and other non-psychological therapies were eligible comparators. Two review authors independently reviewed titles, abstracts, and full-text articles; discrepancies were resolved through discussion or addressed by a third author. When available, we used odds ratio (OR) to compare dichotomous data and standardised mean differences (SMD) to analyse continuous data, both with 95% confidence intervals (CI). We undertook meta-analysis when treatments, participants, and the underlying clinical question were adequately similar. Otherwise, we undertook a narrative analysis. We included five trials of three interventions (Breathe Easier Online, Web-MAP, and multimodal cognitive behavioural therapy (CBT)), which included 463 participants aged 10 to 18 years. Each trial contributed to at least one meta-analysis. Trials involved children and adolescents with long-term physical conditions, such as chronic headache (migraine, tension headache, and others), chronic pain conditions (abdominal, musculoskeletal, and others), chronic respiratory illness (asthma, cystic fibrosis, and others), and symptoms of anxiety or depression. Participants were recruited from community settings and hospital clinics in high income countries.For the primary outcome of change in depression symptoms versus any control, there was very low-quality evidence meaning that it could not be determined whether e-health interventions were clearly better than any comparator (SMD -0.06, 95% CI -0.35 to 0.23; five RCTs, 441 participants). For the primary outcome of change in anxiety symptoms versus any comparator, there was very low-quality evidence meaning that it could not be determined whether e-health interventions were clearly better than any comparator (SMD -0.07, 95% CI -0.29 to 0.14; two RCTs, 324 participants). For the primary outcome of treatment acceptability, there was very low-quality evidence that e-health interventions were less acceptable than any comparator (SMD 0.46, 95% CI 0.23 to 0.69; two RCTs, 304 participants).For the secondary outcome of quality of life, there was very low-quality evidence meaning that it could not be determined whether e-health interventions were clearly better than any comparator (SMD -0.83, 95% CI -1.53 to -0.12; one RCT, 34 participants). For the secondary outcome of functioning, there was very low-quality evidence meaning that it could not be determined whether e-health interventions were clearly better than any comparator (SMD -0.08, 95% CI -0.33 to 0.18; three RCTs, 368 participants). For the secondary outcome of status of long-term physical condition, there was very low-quality evidence meaning that it could not be determined whether e-health interventions were clearly better than any comparator (SMD 0.06, 95% CI -0.12 to 0.24; five RCTs, 463 participants).The risk of selection bias was considered low in most trials. However, the risk of bias due to inadequate blinding of participants or outcome assessors was considered unclear or high in all trials. Only one study had a published protocol; two trials had incomplete outcome data. All trials were conducted by the intervention developers, introducing another possible bias. No adverse effects were reported by any authors. At present, the field of e-health interventions for the treatment of anxiety or depression in children and adolescents with long-term physical conditions is limited to five low quality trials. The very low-quality of the evidence means the effects of e-health interventions are uncertain at this time, especially in children aged under 10 years.Although it is too early to recommend e-health interventions for this clinical population, given their growing number, and the global improvement in access to technology, there appears to be room for the development and evaluation of acceptable and effective technologically-based treatments to suit children and adolescents with long-term physical conditions.