Cognitive behavioural therapy without medication for schizophrenia

Background Cognitive behavioural therapy (CBT) can be effective in people with schizophrenia when provided in combination with antipsychotic medication. It remains unclear whether CBT could be safely and effectively offered in the absence of concomitant antipsychotic therapy. Objectives To investigate the effects of CBT for schizophrenia when administered without concomitant pharmacological treatment with antipsychotics. Search methods We conducted a systematic search on 6 March 2022 in the Cochrane Schizophrenia Group's Study‐Based Register of Trials, which is based on CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, PubMed, ClinicalTrials.gov, and WHO ICTRP. Selection criteria We included randomised controlled trials (RCTs) in people with schizophrenia comparing CBT without antipsychotics to standard care, standard care without antipsychotics, or the combination of CBT and antipsychotics. Data collection and analysis Two review authors independently screened references for inclusion, extracted data from eligible studies, and assessed risk of bias using Cochrane's RoB 2 tool. We contacted study authors for missing data and additional information. Our primary outcome was general mental state measured with a validated rating scale. Key secondary outcomes were specific symptoms of schizophrenia, relapse, service use, number of participants leaving the study early, functioning, quality of life, and number of participants actually receiving antipsychotics during the trial. We also assessed behaviour, adverse effects, and mortality. Main results We included 4 studies providing data for 300 participants (average age 21.94 years). The mean sample size was 75 participants (range 61 to 90 participants). Study duration was between 26 and 39 weeks for the intervention period and 26 to 104 weeks for the follow‐up period. Three studies employed a blind rater, while one study was triple‐blind. All analyses included data from a maximum of three studies. The certainty of the evidence was low or very low for all outcomes. For the primary outcome overall symptoms of schizophrenia, results showed a difference favouring CBT without antipsychotics when compared to no specific treatment at long term (> 1 year mean difference measured with the Positive and Negative Syndrome Scale (PANSS MD) −14.77, 95% confidence interval (CI) −27.75 to −1.79, 1 RCT, n = 34). There was no difference between CBT without antipsychotics compared with antipsychotics (up to 12 months PANSS MD 3.38, 95% CI −2.38 to 9.14, 2 RCTs, n = 63) (very low‐certainty evidence) or compared with CBT in combination with antipsychotics (up to 12 months standardised mean difference (SMD) 0.30, 95% CI −0.06 to 0.65, 3 RCTs, n = 125). Compared with no specific treatment, CBT without antipsychotics was associated with a reduction in overall symptoms (as described above) and negative symptoms (PANSS negative MD −4.06, 95% CI −7.50 to −0.62, 1 RCT, n = 34) at longer than 12 months. It was also associated with a lower duration of hospital stay (number of days in hospital MD −22.45, 95% CI −28.82 to −16.08, 1 RCT, n = 74) and better functioning (Personal and Social Performance Scale MD −12.42, 95% CI −22.75 to −2.09, 1 RCT, n = 40, low‐certainty evidence) at up to 12 months. We did not find a difference between CBT and antipsychotics in any of the investigated outcomes, with the exception of adverse events measured with the Antipsychotic Non‐Neurological Side‐Effects Rating Scale (ANNSERS) at both 6 and 12 months (MD −4.94, 95% CI −8.60 to −1.28, 2 RCTs, n = 48; MD −6.96, 95% CI −11.55 to −2.37, 2 RCTs, n = 42). CBT without antipsychotics was less effective than CBT combined with antipsychotics in reducing positive symptoms at up to 12 months (SMD 0.40, 95% CI 0.05 to 0.76, 3 RCTs, n = 126). CBT without antipsychotics was associated with a lower number of participants experiencing at least one adverse event in comparison with CBT combined with antipsychotics at up to 12 months (risk ratio 0.36, 95% CI 0.17 to 0.80, 1 RCT, n = 39, low‐certainty evidence). Authors' conclusions This review is the first attempt to systematically synthesise the evidence about CBT delivered without medication to people with schizophrenia. The limited number of studies and low to very low certainty of the evidence prevented any strong conclusions. An important limitation in the available studies was that participants in the CBT without medication group (about 35% on average) received antipsychotic treatment, highlighting the challenges of this approach. Further high‐quality RCTs are needed to provide additional data on the feasibility and efficacy of CBT without antipsychotics.