Psychosocial interventions versus antipsychotics for early-onset psychosis: can we fill the evidence gap?
Authors: Sameer Jauhar
Journal: The Lancet Psychiatry (2020)

For anyone working in mental health, few clinical presentations are more poignant than an adolescent presenting for the first time with distressing symptoms of psychotic illness. Treatments are similar to those for adults, and include pharmacotherapy and psychotherapy, as well as broader psychosocial support via multidisciplinary teams, such as first-episode psychosis teams. Pharmacotherapy consists of antipsychotics, with some evidence of both effectiveness and side-effects. Side-effects can range from weight gain and metabolic syndrome to movement disorder.1Barnes TR Drake R Paton C et al.Evidence-based guidelines for the pharmacological treatment of schizophrenia: updated recommendations from the British Association for Psychopharmacology.J Psychopharmacol. 2020; 34: 3-78Crossref PubMed Scopus (90) Google Scholar Most trials testing interventions in early-onset psychosis have been in people with schizophrenia spectrum disorders.2Pagsberg AK Tarp S Glintborg D et al.Acute antipsychotic treatment of children and adolescents with schizophrenia-spectrum disorders: a systematic review and network meta-analysis.J Am Acad Child Adolesc Psychiatry. 2017; 56: 191-202Summary Full Text Full Text PDF PubMed Scopus (57) Google Scholar Psychosocial interventions, such as family intervention and cognitive behavioural therapy, are suggested in current guidelines as adjuncts,3National Institute for Health and Care ExcellencePsychosis and schizophrenia in children and young people: recognition and management. Clinical guideline CG155.https://www.nice.org.uk/guidance/cg155Date: Oct 26, 2016Date accessed: June 29, 2020Google Scholar although, as with antipsychotics, the evidence base is sparse4Anagnostopoulou N Kyriakopoulos M Alba A Psychological interventions in psychosis in children and adolescents: a systematic review.Eur Child Adolesc Psychiatry. 2019; 28: 735-746Crossref PubMed Scopus (14) Google Scholar and guidance borrows heavily from literature on adults. To enable clinical decision making, clinicians, patients, and their families need to know what interventions work for whom, enabling them to balance the risks and benefits. As such, additions to the evidence base are necessary. In a three-arm, randomised, controlled feasibility trial published in The Lancet Psychiatry, Anthony P Morrison and colleagues examined psychosocial intervention (cognitive behavioural therapy [CBT] and family intervention), antipsychotics, and the combination of psychosocial intervention and antipsychotics in people aged 14–18 years with early-onset psychosis.5Morrison AP Pyle M Maughan D et al.Antipsychotic medication versus psychological intervention versus a combination of both in adolescents with first-episode psychosis (MAPS): a multicentre, three-arm, randomised controlled pilot and feasibility study.Lancet Psychiatry. 2020; (published online July 7.)https://doi.org/10.1016/S2215-0366(20)30248-0Summary Full Text Full Text PDF PubMed Scopus (32) Google Scholar The aims were clear—to provide data to serve as a basis for a definitive trial, which would guide the field. Primary outcomes were measures of feasibility and PANSS total score at 6 months. Although the trial did not recruit to the target population size (90 patients), the authors were able to recruit a notable sample (61 patients), within a short period (approximately 18 months), and improvement in PANSS total was seen in all groups. Therefore, at first look, this study is a welcome addition to the sparse literature and should be followed by a larger trial. However, on closer inspection, the trial raises as many questions as it answers. These questions relate to the sample, and specific and non-specific effects of the interventions. The inclusion criteria were broad: help-seeking individuals attending services with psychotic symptoms lasting at least 1 week (PANSS score of moderate, ie ≥4 on the delusions and hallucinations subscales). Crucially, no diagnostic interview was done, with case records listing most diagnoses as ICD-10 code F29 (unspecified non-organic psychosis). Why should this matter? Let us take hallucinations as an example. Hallucinations are common and can be non-pathological in adolescents; a median prevalence estimate from a meta-analysis of 19 population-based studies in adolescents (aged 13–18 years) is 7·5%.6Kelleher I Connor D Clarke MC Devlin N Harley M Cannon M Prevalence of psychotic symptoms in childhood and adolescence: a systematic review and meta-analysis of population-based studies.Psychol Med. 2012; 42: 1857-1863Crossref PubMed Scopus (385) Google Scholar Hallucinations and other psychotic symptoms are seen in various diagnostic constructs, from schizophrenia spectrum and affective disorders, to post-traumatic stress disorder (PTSD) and autistic spectrum disorder, all of which have differing trajectories, co-morbidities, and treatment responses. Combining the individual disorders under psychosis assumes treatment responses for psychotic disorders are similar, irrespective of diagnostic construct. This approach would equate a young person with a diagnostic construct of schizophrenia, a neurodevelopmental history, and positive, negative, and cognitive symptoms, to a young person with PTSD and intermittent auditory hallucinations, conceivably construed as psychotic symptoms secondary to PTSD. In the first scenario, antipsychotics would seem reasonable—potentially with clozapine in the case of treatment-resistant symptoms, which can occur in adolescents with early-onset psychosis7Downs JM Lechler S Dean H et al.The association between comorbid autism spectrum disorders and antipsychotic treatment failure in early-onset psychosis: a historical cohort study using electronic health records.J Clin Psychiatry. 2017; 78: e1233-e1241Crossref PubMed Scopus (27) Google Scholar—whereas, in the second scenario, psychosocial interventions would conceivably be offered first, with emphasis on therapies such as trauma-focused CBT. Even then, the evidence base for either intervention is limited in adolescents with early-onset psychosis, and therein lies reasoning for a trial, and why the current feasibility trial falls short. Addressing these clinical questions will require samples of adequately powered homogenous groups. In the current feasibility study, the rates of diagnoses are unknown without a diagnostic interview. Put simply, and leaving out concerns about diagnostic uncertainty, if we wish to determine if a treatment is effective in a psychotic disorder, we need to measure it in that psychotic disorder. A final issue in the trial design is the absence of a psychological placebo group. In the study, all interventions were associated with adverse effects. Without a placebo group, the true magnitude of these effects and their association with the interventions are unknown. Furthermore, empirically, a future trial should address if the interventions confer additional benefits to general psychosocial support. This knowledge can only be provided by inclusion of a psychological placebo group. This need was highlighted in commentaries on two similar trials in adults, and the addition of a placebo group was suggested for future studies.8Howes O Cognitive therapy: at last an alternative to antipsychotics?.Lancet. 2014; 383: 1364-1366Summary Full Text Full Text PDF PubMed Scopus (9) Google Scholar, 9Jauhar S Cognitive behavioural therapy—a valid alternative to antipsychotics for psychosis?.Lancet Psychiatry. 2018; 5: 381-383Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar Similarly, a pill placebo could be considered if a specific diagnostic group were to be included, for instance, patients with secondary psychotic symptoms in PTSD, in whom evidence for the efficacy of pharmacotherapy is scarce. The field urgently needs a large-scale trial in early-onset psychosis, although if such a trial is to provide clinically meaningful results, it will need to focus on clinically homogenous groups, and differentiate treatment effects. This line of investigation might take time and more than one study, but the results would have wide-ranging and lasting consequences. I have received honoraria from Sunovian, for educational talks. King's College London has received fees for lectures I have given for Lundbeck. I have been a co-investigator for a compound marketed by Alkermes. I am thankful to Dr Robert McCutcheon who advised on some aspects of the commentary. Antipsychotic medication versus psychological intervention versus a combination of both in adolescents with first-episode psychosis (MAPS): a multicentre, three-arm, randomised controlled pilot and feasibility studyThis trial is the first to show that a head-to-head clinical trial comparing psychological intervention, antipsychotics, and their combination is safe in young people with first-episode psychosis. However, the feasibility of a larger trial is unclear because of site-specific recruitment challenges, and amendments to trial design would be needed for an adequately powered clinical and cost-effectiveness trial that provides robust evidence. Full-Text PDF Open Access