T204. CLOZAPINE COMBINATION AND AUGMENTATION STRATEGIES IN PATIENTS WITH SCHIZOPHRENIA –RECOMMENDATIONS FROM AN INTERNATIONAL EXPERT SURVEY AMONG THE TREATMENT RESPONSE AND RESISTANCE IN PSYCHOSIS (TRRIP) WORKING GROUP

BACKGROUND: Evidence for the management of inadequate clinical response to clozapine in treatment-resistant schizophrenia is sparse. Accordingly, an international initiative aimed to develop consensus recommendations for treatment strategies for clozapine-refractory patients with schizophrenia. METHODS: We conducted an online survey among members of the Treatment Response and Resistance in Psychosis (TRRIP) working group. An agreement threshold of ≥75% (responses “agree”+“strongly agree”) was set to define a first-round consensus. Questions achieving agreement or disagreement proportions of >50% in the first round, were re-presented to develop second-round final consensus recommendations. RESULTS: From a total of 61 TRRIP members 44 (first round) and 49 (second round) participated in the consensus-process. Expert recommendations included raising clozapine plasma levels to ≥350 ng/mL for refractory positive, negative and mixed symptoms. In case of ineffective plasma level-guided dose escalation waiting for a delayed response was recommended for persistent positive symptoms. For ongoing clozapine-refractory positive symptoms, combination with a second antipsychotic, (amisulpride and oral aripiprazole) and augmentation with ECT achieved consensus. For clozapine-refractory negative symptoms, waiting for a delayed response was recommended, and as an intervention, clozapine augmentation with an antidepressant reached consensus. For clozapine-refractory suicidality, augmentation with antidepressants or mood-stabilisers, and ECT met consensus criteria. For aggression, augmentation with a mood-stabiliser or combination with antipsychotic medication achieved consensus. Generally, cognitive-behavioural therapy (CBT) and psychosocial interventions reached consensus. DISCUSSION: This consensus-based series of recommendations provides a framework for decision-making to manage the challenging clinical situation of CRS, where the evidence from randomised-controlled trials remains sparse.