Relative Effectiveness of Cognitive Behavior Therapy, Antipsychotics and the Combination for People with First Episode Psychosis: A Two-Study Pooled Analysis of Individual Participant Data

Background There is little head-to-head data comparing cognitive behavior therapy for psychosis (CBTp) and antipsychotic medication (APs). However, several recent trials have been conducted in first episode psychosis. We report a pre-specified individual participant data (IPD) pooled analysis utilizing data from two randomized controlled trials (RCTs) with similar designs to examine relative effectiveness. Study Design The outcomes were psychiatric symptoms (Positive and Negative Syndrome Scale: PANSS) and recovery (Questionnaire about the Process of Recovery: QPR) at 6 months. One-stage and two-stage IPD meta-analyses were performed based on the intention-to-treat principle. Serious adverse events are also summarized. Study Results Two RCTs were included in the pooled IPD analysis which provided 136 participants. For PANSS total at 6 months, the one-stage meta-analysis found no evidence of a difference between CBTp alone and APs alone (mean difference 2.58, 95% CI, -2.83 to 7.98; P-value 0.35) and CBTp alone compared with APs plus CBTp (MD -5.91; 95% CI, -12.14 to 0.31; P-value 0.063). For APs alone compared to CBTp plus APs there was evidence of a difference (MD -8.49; 95% CI, -14.65 to -2.33; P-value 0.007) favoring the combined treatment. For user-defined recovery (QPR), there was a difference favoring CBTp plus APs in comparison to both CBTp alone (P-value 0.029) and APs alone (P-value 0.026), but no difference between the monotherapies (P-value 0.91). The most common serious adverse events were psychiatric hospital admissions. Conclusions Cognitive behavior therapy for psychosis and APs did not differ in their effects on symptoms or recovery, but there were suggestions that the combined treatment may be superior. A definitive RCT is warranted.