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

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.

Time to treatment response in first-episode schizophrenia: should acute treatment trials last several months?

OBJECTIVE: Response patterns may differ between patients with first-episode and multiepisode schizophrenia. This analysis explored trial duration with first-episode patients and asked whether early limited improvement predicts ultimate lack of treatment response with first-episode patients as it does with multiepisode patients. METHOD: One hundred twelve subjects (mean age = 23.3 years, SD = 5.1 years) who presented between November 1998 and October 2004 with a first episode of psychosis and had a DSM-IV diagnosis of schizophrenia or schizophreniform or schizoaffective disorder were randomly assigned to treatment with olanzapine or risperidone for 16 weeks. Treatment response, the primary outcome measure, was defined as a rating of mild or better on all of the positive symptom items on the Schedule for Affective Disorders and Schizophrenia Change Version With Psychosis and Disorganization Items. Response rates were calculated for each study week. A logistic regression analysis examined the association between percentage reduction in symptom severity scores from baseline values at weeks 2, 4, or 8 and response by week 16. The study was conducted at The Zucker Hillside Hospital, Glen Oaks, New York and the Bronx-Lebanon Hospital Center, Bronx, New York. RESULTS: The estimated cumulative response rate was 39.59% (95% CI, 29.77%-49.41%) by week 8 and 65.19% (95% CI, 55.11%-75.27%) by week 16. The confidence intervals for estimated response at weeks 10, 12, 14, and 16 were not distinct. Response rates increased approximately 5 to 6 percentage points each 2-week interval between week 10 and 16. Percentage reduction in symptom severity score at week 4 (but not 2 or 8) was associated (χ²1 = 3.96; P < .05) with responder status at week 16 (odds ratio = 1.03; 95% CI, 1.00-1.05). However, receiver operating characteristic curves did not suggest any level of percentage symptom reduction that would be clinically useful as a predictor of response by week 16. CONCLUSIONS: Many first-episode patients respond between weeks 8 and 16 of treatment with a single antipsychotic medication. Limited early symptom improvement does not identify those first-episode patients who will not improve with a full 16-week trial with enough accuracy to be clinically useful. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000374.

Lack of an inverse relationship between duration of untreated psychosis and cognitive function in first episode schizophrenia.

This study assessed the relationship between duration of untreated psychosis (DUP) and cognitive measures in order to assess if longer DUP was associated with worse performance. One hundred two patients with first episode schizophrenia or schizoaffective disorder were assessed on cognitive measures of speed of processing, episodic memory, executive function, and visual spatial processing at baseline (when patients were drug naive and after 16 weeks of olanzapine or risperidone treatment), so that a change score could be derived. DUP was defined by the emergence of psychiatric symptoms and the emergence of psychotic symptoms. Data were analyzed correlationally, parametrically (after the group was divided into long and short DUP by median split), and by regression. We found that DUP for psychotic symptoms in this group of patients was long, with a median of 46 weeks. Neither correlational, parametric analyses in which DUP served as a class variable, nor multiple regression indicated that longer DUP was associated with worse cognition at baseline or smaller magnitude of improvement in cognition. Our results suggest that while early intervention may be critical for symptom amelioration by shortening DUP, early intervention for treatment of psychiatric symptoms may have little or no impact on cognitive function. Furthermore, assuming that cognition is a core symptom of schizophrenia, the notion that ongoing psychosis is somehow toxic for a variety of information processing domains appears questionable.

Randomized comparison of olanzapine versus risperidone for the treatment of first-episode schizophrenia: 4-month outcomes.

OBJECTIVE: The authors compared 4-month treatment outcomes for olanzapine versus risperidone in patients with first-episode schizophrenia spectrum disorders. METHOD: One hundred twelve subjects (70% male; mean age=23.3 years [SD = 5.1]) with first-episode schizophrenia (75%), schizophreniform disorder (17%), or schizoaffective disorder (8%) were randomly assigned to treatment with olanzapine (2.5-20 mg/day) or risperidone (1-6 mg/day). RESULTS: Response rates did not significantly differ between olanzapine (43.7%, 95% CI=28.8%-58.6%) and risperidone (54.3%, 95% CI=39.9%-68.7%). Among those responding to treatment, more subjects in the olanzapine group (40.9%, 95% CI=16.8%-65.0%) than in the risperidone group (18.9%, 95% CI=0%-39.2%) had subsequent ratings not meeting response criteria. Negative symptom outcomes and measures of parkinsonism and akathisia did not differ between medications. Extrapyramidal symptom severity scores were 1.4 (95% CI=1.2-1.6) with risperidone and 1.2 (95% CI=1.0-1.4) with olanzapine. Significantly more weight gain occurred with olanzapine than with risperidone: the increase in weight at 4 months relative to baseline weight was 17.3% (95% CI=14.2%-20.5%) with olanzapine and 11.3% (95% CI=8.4%-14.3%) with risperidone. Body mass index at baseline and at 4 months was 24.3 (95% CI=22.8-25.7) versus 28.2 (95% CI=26.7-29.7) with olanzapine and 23.9 (95% CI=22.5-25.3) versus 26.7 (95% CI=25.2-28.2) with risperidone. CONCLUSIONS: Clinical outcomes with risperidone were equal to those with olanzapine, and response may be more stable. Olanzapine may have an advantage for motor side effects. Both medications caused substantial rapid weight gain, but weight gain was greater with olanzapine.