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

Abstract

Background Evidence for the effectiveness of treatments in early-onset psychosis is sparse. Current guidance for the treatment of early-onset psychosis is mostly extrapolated from trials in adult populations. The UK National Institute for Health and Care Excellence has recommended evaluation of the clinical effectiveness and cost-effectiveness of antipsychotic drugs versus psychological intervention (cognitive behavioural therapy [CBT] and family intervention) versus the combination of these treatments for early-onset psychosis. The aim of this study was to establish the feasibility of a randomised controlled trial of antipsychotic monotherapy, psychological intervention monotherapy, and antipsychotics plus psychological intervention in adolescents with first-episode psychosis.Methods We did a multicentre pilot and feasibility trial according to a randomised, single-blind, three-arm, controlled design. We recruited participants from seven UK National Health Service Trust sites. Participants were aged 14-18 years; help-seeking; had presented with first-episode psychosis in the past year; were under the care of a psychiatrist; were showing current psychotic symptoms; and met ICD-10 criteria for schizophrenia, schizoaffective disorder, or delusional disorder, or met the entry criteria for an early intervention for psychosis service. Participants were assigned (1:1:1) to antipsychotics, psychological intervention (CBT with optional family intervention), or antipsychotics plus psychological intervention. Randomisation was via a web-based randomisation system, with permuted blocks of random size, stratified by centre and family contact. CBT incorporated up to 26 sessions over 6 months plus up to four booster sessions, and family intervention incorporated up to six sessions over 6 months. Choice and dose of antipsychotic were at the discretion of the treating consultant psychiatrist. Participants were followed up for a maximum of 12 months. The primary outcome was feasibility (ie, data on trial referral and recruitment, session attendance or medication adherence, retention, and treatment acceptability) and the proposed primary efficacy outcome was total score on the Positive and Negative Syndrome Scale (PANSS) at 6 months. Primary outcomes were analysed by intention to treat. Safety outcomes were reported according to as-treated status, for all patients who had received at least one session of CBT or family intervention, or at least one dose of antipsychotics. The study was prospectively registered with ISRCTN, ISRCTN80567433. Findings Of 101 patients referred to the study, 61 patients (mean age 16•3 years [SD 1•3]) were recruited fromApril 10, 2017, to Oct 31, 2018, 18 of whom were randomly assigned to psychological intervention, 22 to antipsychotics, and 21 to antipsychotics plus psychological intervention. The trial recruitment rate was 68% of our target sample size of 90 participants. The study had a low referral to recruitment ratio (around 2:1), a high rate of retention (51 [84%] participants retained at the 6-mon...

Mindfulness‐based cognitive therapy and depression relapse—evaluating evidence through a meta‐analytic lens may indicate myopia

“…A number of RCTs have been conducted where people with schizophrenia or psychosis are offered CBT as an alternative to antipsychotics, utilising TAU comparator groups. These have included CBT versus antipsychotics (TAU) or a combination of both 13,14 (or a combination of CBT plus family therapy versus antipsychotics or both) 15 . The results of these trials have led some to suggest that ‘patient choice’ should include the use of this intervention in place of antipsychotic medication (cited in the current meta‐analysis).…”

“…All of these trials have been conducted by the same research group (Morrison and colleagues) and have TAU as comparator (with no active psychological placebo). One trial showed a significant difference between CBT and TAU, with 37 people in each arm, 13 one an advantage for CBT plus antipsychotics over CBT alone, 14 and one (feasibility study) showed no difference between psychosocial interventions and TAU in adolescents with psychosis 15 …”

Service-user efforts to maintain their wellbeing during and after successful withdrawal from antipsychotic medication

“…These findings are consistent with the existing qualitative research suggesting a ‘safety net’ of information, strategies and supports is needed to successfully withdraw from antipsychotics. 5 , 18 , 19 , 25 , 27 , 53 However, studies of attempted withdrawal show people frequently lack the information, skills and support needed to build this kind of safety net, 18 , 26 , 52 and often taper off too rapidly, relapse and resume the medication. 11 , 17 , 24 The reverse was true for this group.…”

“… 47 , 48 A number of studies suggest that talking therapy and other psycho-social interventions improve outcomes among those who experience psychosis and represent promising alternatives to antipsychotic treatment, but withdrawal research typically overlooks these treatments and their targets as potential covariates. 49 - 54 …”

“…To our knowledge only one small qualitative study has specifically explored how people who successfully stop taking antipsychotics manage the process. 27 Furthermore, most studies that explore the psycho-social efforts of those who stop taking antipsychotics limit their investigations to the decision-making process and the strategies and supports currently in place, 18 , 19 , 42 , 52 , 53 but neglect to explore the critical withdrawal period or account for the evidence regarding the differential and interactive effects of various coping styles, cognitive processes and environments. These issues were addressed in the present study, in which interviews were conducted with people who had stopped taking antipsychotic medication successfully and believed themselves to be managing well.…”