Multimodal prevention of first psychotic episode through N-acetyl-l-cysteine and integrated preventive psychological intervention in individuals clinically at high risk for psychosis: Protocol of a randomized, placebo-controlled, parallel-group trial.

Aim Meta-analyses indicate positive effects of both antipsychotic and cognitive-behavioural interventions in subjects clinically at high risk (CHR) for psychosis in terms of a delay or prevention of psychotic disorders. However, these effects have been limited regarding social functioning and the relative efficacy of both types of interventions remains unclear. Furthermore, neuroprotective substances seem to be a promising alternative agent in psychosis-prevention as they are associated with few and weak side-effects. Methods In this multi-centre randomized controlled trial (RCT), we investigate the effects of two interventions on transition to psychosis and social functioning: (a) an integrated preventive psychological intervention (IPPI) including stress-/symptom-management and social-cognitive remediation; (b) N-acetyl-l-cysteine (NAC) as a pharmacological intervention with glutamatergic, neuroprotective and anti-inflammatory capabilities. Results This is a double-blind, placebo-controlled RCT with regard to NAC and a single-blind RCT with regard to IPPI using a 2 x 2-factorial design to investigate the individual and combined preventive effects of both interventions. To this aim, a total of 200 CHR subjects will be randomized stratified by site to one of four conditions: (a) IPPI and NAC; (b) IPPI and Placebo; (c) NAC and psychological stress management; (d) Placebo and psychological stress management. Interventions are delivered over 26 weeks with a follow-up period of 12 months. Conclusion This paper reports on the rationale and protocol of an indicated prevention trial to detect the most effective and tolerable interventions with regard to transition to psychosis as well as improvements in social functioning, and to evaluate the synergistic effects of these interventions.