Structured psychiatric care and psychosocial support during placebo participation: association with violent and domestic-violence offending in the ReINVEST trial.

BACKGROUND: Participants in the ReINVEST randomized placebo-controlled trial of sertraline, conducted among men with high trait impulsivity and histories of violent offending, received structured clinical contact throughout the trial, including psychiatric assessments, nursing consultations, crisis support, and referrals to mental health and external services. We estimated the association between placebo trial participation and violent and domestic-violence reoffending, compared with non-participation after baseline and single-blind run-in. METHODS: This prespecified secondary analysis included men from the ReINVEST trial pathway who completed baseline assessment and entered the single-blind run-in phase but did not proceed to randomization, to inform the counterfactual. Violent and domestic-violence offences were identified from linked administrative records over 12- and 24-month follow-up periods. Adjusted differences, targeting the average treatment effect on the treated (ATT), were estimated using g-computation after common-support restriction, with entropy balancing as a second estimator. RESULTS: Placebo trial participation was associated with lower offending across both outcome domains and follow-up periods. Placebo-standardized mean count differences for violent offending were -0.19 (95% confidence interval [CI] -0.38, -0.04) at 12 months and -0.22 (95% CI -0.51, -0.05) at 24 months. Corresponding differences for domestic-violence offending were -0.37 (95% CI -0.81, -0.14) at 12 months and -0.49 (95% CI -0.92, -0.22) at 24 months. The association was more apparent among men with a documented psychiatric history and, for domestic-violence offending, among those with higher baseline anger, irritability and aggression. Pre-randomization referrals did not explain selection into placebo participation or materially alter the estimates. Post-randomization referrals were observed in both groups, remained more common in the placebo group, and did not account for the observed association. CONCLUSION: Placebo participation in this trial involved sustained clinical contact and psychosocial support beyond exposure to inactive medication, and the findings are consistent with a contribution of these non-pharmacological components to lower reoffending. In placebo-controlled trials involving populations with high psychiatric morbidity and limited continuity of coordinated care, the clinical content of placebo participation should be explicitly characterized in trial design and interpretation. CLINICAL TRIAL REGISTRATION: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?, identifier ACTRN12613000442707.