Antipsychotic drugs versus cognitive behavioural therapy versus a combination of both in people with psychosis: a randomised controlled pilot and feasibility study

Abstract

SummaryBackgroundLittle evidence is available for head-to-head comparisons of psychosocial interventions and pharmacological interventions in psychosis. We aimed to establish whether a randomised controlled trial of cognitive behavioural therapy (CBT) versus antipsychotic drugs versus a combination of both would be feasible in people with psychosis.MethodsWe did a single-site, single-blind pilot randomised controlled trial in people with psychosis who used services in National Health Service trusts across Greater Manchester, UK. Eligible participants were aged 16 years or older; met ICD-10 criteria for schizophrenia, schizoaffective disorder, or delusional disorder, or met the entry criteria for an early intervention for psychosis service; were in contact with mental health services, under the care of a consultant psychiatrist; scored at least 4 on delusions or hallucinations items, or at least 5 on suspiciousness, persecution, or grandiosity items on the Positive and Negative Syndrome Scale (PANSS); had capacity to consent; and were help-seeking. Participants were assigned (1:1:1) to antipsychotics, CBT, or antipsychotics plus CBT. Randomisation was done via a secure web-based randomisation system (Sealed Envelope), with randomised permuted blocks of 4 and 6, stratified by gender and first episode status. CBT incorporated up to 26 sessions over 6 months plus up to four booster sessions. Choice and dose of antipsychotic were at the discretion of the treating consultant. Participants were followed up for 1 year. The primary outcome was feasibility (ie, data about recruitment, retention, and acceptability), and the primary efficacy outcome was the PANSS total score (assessed at baseline, 6, 12, 24, and 52 weeks). Non-neurological side-effects were assessed systemically with the Antipsychotic Non-neurological Side Effects Rating Scale. Primary analyses were done by intention to treat; safety analyses were done on an as-treated basis. The study was prospectively registered with ISRCTN, number ISRCTN06022197.FindingsOf 138 patients referred to the study, 75 were recruited and randomly assigned—26 to CBT, 24 to antipsychotics, and 25 to antipsychotics plus CBT. Attrition was low, and retention high, with only four withdrawals across all groups. 40 (78%) of 51 participants allocated to CBT attended six or more sessions. Of the 49 participants randomised to antipsychotics, 11 (22%) were not prescribed a regular antipsychotic. Median duration of total antipsychotic treatment was 44·5 weeks (IQR 26–51). PANSS total score was significantly reduced in the combined intervention group compared with the CBT group (–5·65 [95% CI −10·37 to −0·93]; p=0·019). PANSS total scores did not differ significantly between the combined group and the antipsychotics group (–4·52 [95% CI −9·30 to 0·26]; p=0·064) or between the antipsychotics and CBT groups (–1·13 [95% CI −5·81 to 3·55]; p=0·637). Significantly fewer side-effects, as measured with the Antipsychotic Non-neurological Side Effects Rating Scale, were noted in the CBT group than in ...

Response rates in patients with schizophrenia and positive symptoms receiving cognitive behavioural therapy: a systematic review and single-group meta-analysis

“…As a result, it is not possible to ascertain the respective role of cognitive behavioural therapy and medication on the outcome, neither to evaluate the adequacy of the pharmacotherapy provided in combination with CBT. Moreover, administration of CBT to patients with schizophrenia without concomitant antipsychotic medication is a debated issue: some studies have been conducted by Morrison et al in patients receiving CBT without medication [ 24 , 28 , 29 ], but other authors have claimed this to be unethical [ 30 ]. We argue that the situation in the studies included in the present review resembles real-life clinical practice settings, where patients, in general, receive antipsychotics in addition to CBT, making our results more generalizable to the clinical context.…”

Psychosocial interventions for people with schizophrenia or psychosis on minimal or no antipsychotic medication: A systematic review

“…Harms: In Morrison et al (2014) 8 serious adverse events were reported, 2 in the CBT group and 6 in the control group and 2 participants in each group were judged to have a deterioration. In Morrison et al (2018) adverse side-effects (e.g. sleep or memory problems) were less common in the CBT group than the antipsychotics group (p=.017).…”

“…Few studies described how the treatment delivered was standardised and how quality of implementation was assured. The trials of CBT used regular supervision, rated recordings of sessions with a cognitive therapy scale (Blackburn et al, 2001), and reviewed written, structured session records (Morrison et al, 2018(Morrison et al, , 2014. Results are grouped by intervention, including a brief general summary of each intervention.…”

“…Results: Two single blind RCTs have been conducted (Morrison et al, 2018(Morrison et al, , 2014. The first RCT found that CBT compared to an antipsychotic-free treatment as usual control group, significantly reduced the primary outcome, symptoms of psychosis at moderate effect (d=0.5, p=0.003), and improved social function (Est=5.47, p=0.04) (Morrison et al, 2014).…”

“…During the study, in both groups 10/37 people were prescribed antipsychotics. The second RCT compared CBT to an antipsychotic only control group (Morrison et al, 2018). No differences between the groups were found for symptoms of psychosis or social function.…”