Efficacy and Safety of Pharmacological and Psychological Interventions for the Treatment of Psychosis and Schizophrenia in Children, Adolescents and Young Adults: A Systematic Review and Meta-Analysis

February Efficacy and Safety of Pharmacological and Psychological Interventions for the Treatment of Psychosis and Schizophrenia in Children, Adolescents and Young Adults: A Systematic Review and Meta-Analysis Megan R. Stafford 0 1 Evan Mayo-Wilson 0 1 Christina E. Loucas 0 1 Anthony James 0 1 Chris Hollis 0 1 Max Birchwood 0 1 Tim Kendall 0 1 0 1 National Collaborating Centre for Mental Health (NCCMH), Royal College of Psychiatrists , London , United Kingdom , 2 Centre for Outcomes, Research & Effectiveness (CORE), University College London , London , United Kingdom , 3 Highfield Adolescent Unit, Warneford Hospital , Oxford , United Kingdom , 4 Faculty of Medicine & Health Sciences, Queen's Medical Centre , Nottingham , United Kingdom , 5 Division of Mental Health and Wellbeing, Warwick Medical School, University of Warwick , Coventry , United Kingdom 1 Academic Editor: Inez Myin-Germeys, Maastricht University , NETHERLANDS - Funding: This work was supported by the National Collaborating Centre for Mental Health and conducted as part of a guideline about psychosis in children, adolescents and young adults. The full review protocol is available from the authors. TK receives 1.4 million per year for the National Collaborating Centre for Mental Health from the National Institute for Health and Clinical Excellence to cents and young adults. Studies report contrasting results regarding the efficacy and safety of pharmacological, psychological, and combined interventions in psychosis and schizophrenia in children, adolesSystematic review and meta-analysis. Embase, Medline, PreMedline, PsycINFO, and CENTRAL were searched to July 2013 without restriction to publication status. Randomised trials comparing any pharmacological, psychological, or combined intervention for psychosis and schizophrenia in children, adolescents and young adults were included. Studies were assessed for bias, and GRADE criteria were used to describe the quality of the results. Twenty-seven trials including 3067 participants were identified. Meta-analyses were performed for 12 comparisons: symptoms, relapse, global state, psychosocial functioning, depression, weight and discontinuation. Low quality evidence demonstrated that no trials of psychological treatments in under-18 year olds. There was no evidence of an effect of psychological interventions on psychotic symptoms in an acute episode, or relapse develop guidelines for the treatment of mental health problems (https://www.nice.org.uk/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: This work was supported by the National Collaborating Centre for Mental Health and conducted as part of a guideline about psychosis in children, adolescents and young adults. The full review protocol is available from the authors. All authors contributed to the 23 development of the review questions. MRS drafted the review protocol. Sarah Stockton, of the National Collaborating Centre for Mental Health, designed and implemented the searches. MRS, EMW and CEL assessed the eligibility of the studies for inclusion and extracted data. MRS and EMW assessed risk of bias and applied GRADE criteria. The authors would like to acknowledge the support of Hannah Jackson, who worked at the National Collaborating Centre for Mental Health as a research assistant, during guideline development. All authors contributed to the analyses, the writing of the manuscript and agreed on the final draft. All authors had full access to the data (including statistical results and tables) and take responsibility for the integrity of the data and accuracy of the analysis. This does not alter the authors adherence to PLOS ONE policies on sharing data and materials. rate, but low quality evidence of a large effect for family plus individual CBT on the number of days to relapse (WMD = 32.25, 95% CI -36.52 to -27.98). For children, adolescents and young adults, the balance of risk and benefit of antipsychotics appears less favourable than in adults. Research is needed to establish the potential for psychological treatments, alone and in combination with antipsychotics, in this population. Early-onset schizophrenia, that is, schizophrenia occurring prior to 17 years [1], affects approximately 1.6 to 1.9 per 100,000 of the child and adolescent population [25]. It is a severe and debilitating disorder associated with considerable long-term impairments in psychological, social, educational and occupational functioning [6], poor physical health, reduced life expectancy [7,8], and substantial direct and indirect costs [9,10]). Compared with adult-onset schizophrenia, early-onset schizophrenia may be a more severe disorder, negatively influencing social, cognitive and psychological development [6]. While antipsychotic medications play an integral role in the treatment and management of schizophrenia in children, adolescents and young adults, the nature of adverse effects that can follow first exposure occurs during a vulnerable phase of physical growth and brain development, and at a time when young people may be particularly vulnerable to rapid weight gain [11] and disturbances to the cardiometabolic system [12,13], bone growth [14] and sexual development [15]. Such health risks raise important public health concerns given the widespread use of these medications [16]. Furthermore, children, adolescents and young adults are more likely than adults to exhibit negative symptoms, and less likely to exhibit systematized delusions and hallucinations [17]. This has implications for the potential efficacy in children, adolescents and young adults of psychological interventions developed for adults with psychosis or schizophrenia. The increased recognition of the limitations associated with antipsychotic medication has stimulated greater interest in psychological interventions in this population [18]. A recent systematic review of interventions for people who do not have established psychosis, found that psychological interventions may have a positive impact if delivered before the onset of psychosis in individuals with attenuated or transient psychotic symptoms [19]. Additionally, demand for psychological therapies in general has also grown. In England, this has culminated in the Department of Healths Improving Access to Psychological Therapies (IAPT) initiative, which is set to receive further funding to extend to children, adolescent and young adults and to those with major mental health problems, particularly schizophrenia, under the UK coalition governments mental health strategy [20]. Finally, families may play an even greater role in providing care and support to children, adolescents and young adults with schizophrenia compared to adults. Given the robust evidence for the efficacy of family interventions in adult schizophrenia [21], these interventions may be particularly promising in children, adolesce (...truncated)