Transdiagnostic therapy for persistent physical symptoms: A mediation analysis of the PRINCE secondary trial

The PRINCE secondary trial did not find any evidence that transdiagnostic cognitive behavioural therapy (TDT-CBT) plus standard medical care (SMC) was more efficacious than SMC for patients with Persistent Physical Symptoms (PPS) for the primary outcome Work and Social Adjustment Scale (WSAS) at final follow-up (52 weeks). There was a significant treatment effect for TDT-CBT plus CBT compared with SMC for two secondary outcomes: WSAS at the end of active treatment (20 weeks) and symptom severity (Patient Health Questionnaire, PHQ-15) at 52 weeks. To understand mechanisms that lead to effects of TDT-CBT plus SMC versus SMC we performed a planned secondary mediation analysis. We investigated whether TDT-CBT treatment effects on these two secondary outcomes at the end of the treatment could be explained by effects on variables that were targeted by TDT-CBT during the initial phase of treatment. We pre-specified mediator variables measured at mid-treatment (9 weeks). Reductions in catastrophising and symptom focusing were the strongest mediators of TDT-CBT treatment effects on WSAS at the end of treatment. Improvements in symptom focusing also mediated the effect of TDT-CBT on PHQ-15. Future developments of the TDT-CBT intervention could benefit from targeting these mediators.