Sequential Multiple-assignment Randomized Trials To Compare Antipsychotic Treatments (SMART-CAT) In First-episode Psychosis Patients

Objectives: To determine the optimal treatment plan for first-episode schizophrenia in China and to define the appropriate treatment strategies for the first-trial failed schizophrenia,especially the value of early use of clozapine.Methods: The study is a randomized controlled clinical multicenter trial which includes two treatment phases(each phase lasting for 8 weeks).First-episode psychosis were enrolled and randomly assigned to olanzapine,risperidone,amisulpride,aripiprazole or perphenazine for 8 weeks in an open-label design.Patients who did not meet response criteria at 8 weeks were randomly assigned to one of the treatments with oral olanzapine,risperidone,amisulpride,aripiprazole or clozapine.Psychotic symptoms were evaluated with positive and negative symptom scale(PANSS),Clinician-Rated Dimensions of Psychosis Symptom severity(CRDPS),Calgary Depression Scale for Schizophrenia(CDSS)and clinical global impression scale(CGI).The Barnes Akathisia Scale(BAS),Simpson-Angus Extrapyramidal Side Effects Scale(SAS)and Abnormal Involuntary Movement Scale(AIMS)are used to assess extrapyramidal adverse reactions,and Arizona Sexual Experiences Scale(ASEX)used for assessing sexual dysfunction.The University of California,San Diego(UCSD)Performance-based Skills Assessment-Brief(UPSA-B)is used to evaluate the social function and the MATRICS consensus cognitive battery(MCCB)is used to evaluate cognitive deficits.Quality of life is assessed by Heinirich Quality of life Scale(HRQOL).In addition,Medication Satisfaction Questionnaire(MSQ) and the Subjective Well-being under Neuroleptics(SWN)are used to assess whether participants are satisfied with their assigned treatments.Results: Between February 2019 and December 2019,we recruited 76 participants who signed informed consent.Of the 65 patients in the intention-to-treat sample,54(83%)completed the eight weeks open label random treatment(16 on olanzapine,9 on risperidone,13 on amisulpride,7 on aripiprazole,9 on perphenazine),and 29(53.7%±6.8%)patients achieved response criteria after phase 1(9 on olanzapine,6 on risperidone,7 on amisulpride,3 on aripiprazole,4 on perphenazine,p=0.86).16 of the 25 patients who were not meet the response criteria continued to the 8-week open-label randomized switching trial,with 14(87.5%)patients completing the trial(3 on olanzapine,6 on risperidone,3 on amisulpride,2 on clozapine),and 11(87.5%)patients achieved response criteria after phase 1(3 on olanzapine,5 on risperidone,2 on amisulpride,1 on perphenazine,p=0.61).Conclusions: Olanzapine,risperidone,amisulpride,aripiprazole and perphenazine were all effective in improving the acute symptoms in FES patients.After medication treatment,the patient’s verbal learning improved.Olanzapine,risperidone,amisulpride,and clozapine can effectively relieve psychotic symptoms in the first-trail failed schizophrenia and a little longer treatment time may be required for first-trail failed schizophrenia.