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

Abstract

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.

Efficacy and Safety of Aripiprazole Once-Monthly in the Maintenance Treatment of Bipolar I Disorder

“…Among the atypical antipsychotics, aripiprazole is known to be prolactin-sparing, whereas others, including risperidone, are considered to be prolactin-raising. 42,48 The present study did not reveal any clinically meaningful alterations in prolactin levels with AOM 400 versus placebo, and there were few TEAEs related to prolactin or sexual dysfunction.…”

Dopamine Targeting Drugs for the Treatment of Schizophrenia: Past, Present and Future

“…Extrapyramidal syndrome is a commonly observed side effect, especially for the first generation antipsychotics, such as haloperidol, which generally require high striatal D 2 receptor occupancy for efficacy and consequently result in motor disturbances such as parkinsonism and akathisia [174, 190]. It has been suggested for first-episode patients that aripiprazole may be considered as the preferred choice over risperidone; however, if the potential for akathisia and poor impulse control is a concern, low-dose risperidone may be a better choice over aripiprazole [191]. Clozapine demonstrated less severe motoric side effects, which is likely due to the relatively lower D 2 receptor occupancy at therapeutic doses [194].…”

Current Data on and Clinical Insights into the Treatment of First Episode Nonaffective Psychosis: A Comprehensive Review

“…This higher discontinuation rate seems to be related not only to extrapyramidal symptoms but also to some other disadvantages of FGAs, as they may produce more secondary negative and cognitive symptoms [32]. Additionally, these negative effects do not seem to be homogeneous among different medications within the SGA group [33, 34]. …”

“…Most of the medium-term randomized studies have shown similar rates of clinical response and all-cause treatment discontinuation in people with a FEP treated with other SGAs (risperidone, olanzapine, ziprasidone, aripiprazole, amisulpride) [28, 31]. Robinson et al [33] showed a similar efficacy and effectiveness between aripiprazole and risperidone for the acute treatment of first-episode schizophrenia. Olanzapine might lead to longer treatment maintenance than haloperidol or ziprasidone in treatment-naïve people with a FEP [40].…”