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

Schizophr Bull. 2026 Jan 16;52(1):sbaf121. doi: 10.1093/schbul/sbaf121.

Abstract

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.

Keywords: CBT; antipsychotics; psychosis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents* / adverse effects
  • Antipsychotic Agents* / pharmacology
  • Cognitive Behavioral Therapy* / methods
  • Cognitive Behavioral Therapy* / statistics & numerical data
  • Combined Modality Therapy
  • Female
  • Humans
  • Male
  • Outcome Assessment, Health Care* / statistics & numerical data
  • Psychotic Disorders* / therapy
  • Randomized Controlled Trials as Topic
  • Schizophrenia* / therapy
  • Young Adult

Substances

  • Antipsychotic Agents