A Randomized Comparison of Aripiprazole and Risperidone for the Acute Treatment of First-Episode Schizophrenia and Related Disorders: 3-Month Outcomes

Schizophr Bull. 2015 Nov;41(6):1227-36. doi: 10.1093/schbul/sbv125. Epub 2015 Sep 3.


Research findings are particularly important for medication choice for first-episode patients as individual prior medication response to guide treatment decisions is unavailable. We describe the first large-scale double-masked randomized comparison with first-episode patients of aripiprazole and risperidone, 2 commonly used first-episode treatment agents. One hundred ninety-eight participants aged 15-40 years with schizophrenia, schizophreniform disorder, schizoaffective disorder or psychotic disorder Not Otherwise Specified, and who had been treated in their lifetime with antipsychotics for 2 weeks or less were randomly assigned to double-masked aripiprazole (5-30 mg/d) or risperidone (1-6 mg/d) and followed for 12 weeks. Positive symptom response rates did not differ (62.8% vs 56.8%) nor did time to response. Aripiprazole-treated participants had better negative symptom outcomes but experienced more akathisia. Body mass index change did not differ between treatments but advantages were found for aripiprazole treatment for total and low-density lipoprotein cholesterol, fasting glucose, and prolactin levels. Post hoc analyses suggested advantages for aripiprazole on depressed mood. Overall, if the potential for akathisia is a concern, low-dose risperidone as used in this trial maybe a preferred choice over aripiprazole. Otherwise, aripiprazole would be the preferred choice over risperidone in most situations based upon metabolic outcome advantages and some symptom advantages within the context of similar positive symptom response between medications.

Trial registration: ClinicalTrials.gov NCT00320671.

Keywords: akathisia; clinical trial; metabolic side effects; negative symptoms; treatment response.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / pharmacology*
  • Aripiprazole / administration & dosage
  • Aripiprazole / adverse effects
  • Aripiprazole / pharmacology*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Outcome Assessment, Health Care*
  • Psychotic Disorders / drug therapy*
  • Risperidone / administration & dosage
  • Risperidone / adverse effects
  • Risperidone / pharmacology*
  • Schizophrenia / drug therapy*
  • Young Adult


  • Antipsychotic Agents
  • Aripiprazole
  • Risperidone

Associated data

  • ClinicalTrials.gov/NCT00320671