Efficacy and tolerability of aripiprazole versus D(2) antagonists in the early course of schizophrenia: a systematic review and meta-analysis

Early intervention is essential for favorable long-term outcomes in schizophrenia. However, there is limited guidance in the scientific literature on how best to choose between dopamine D(2) receptor (D(2)R) partial agonists and D(2)R antagonists in early stages of schizophrenia. The aim of this meta-analysis was to directly compare D(2)R partial agonists with D(2)R antagonists for efficacy and tolerability, using randomized controlled trials (RCTs) that involved participants diagnosed with first-episode psychosis, schizophrenia, or related psychotic disorders with a duration of illness ≤5 years. Fourteen RCTs, involving 2494 patients, were included in the meta-analysis. Aripiprazole was the only identified D(2)R partial agonist, and was not significantly different from pooled D(2)R antagonists for overall symptom reduction or all-cause discontinuation. However, aripiprazole was more favorable than pooled D(2)R antagonists for depressive symptoms, prolactin levels, and triglyceride levels. Specifically, aripiprazole was more favorable than paliperidone for triglyceride levels and more favorable than risperidone and olanzapine, but less favorable than ziprasidone, for weight gain. In addition, aripiprazole was less favorable for akathisia compared with second-generation D(2)R antagonists, in particular olanzapine and quetiapine, and less favorable for discontinuation due to inefficacy than risperidone. Lastly, aripiprazole was more favorable than haloperidol for various efficacy and tolerability outcomes. In conclusion, aripiprazole’s efficacy did not differ substantially from D(2)R antagonists in the early course of schizophrenia, whereas differential tolerability profiles were noted. More double-blind RCTs are required comparing the efficacy and tolerability of aripiprazole as well as other D(2)R partial agonists with D(2)R antagonists in early stages of schizophrenia.