A 12-week, naturalistic switch study of the efficacy and tolerability of aripiprazole in stable outpatients with schizophrenia or schizoaffective disorder

Abstract

The objectives of this 12-week multicenter open-label switching study were to evaluate the overall clinical efficacy, safety, and tolerability of aripiprazole in stable patients with schizophrenia or schizoaffective disorder, and to assess, in a naturalistic setting, whether such patients experience symptom worsening when switched from D2 receptor antagonists to aripiprazole (a D2 receptor partial agonist). Patients with schizophrenia or schizoaffective disorder in a symptomatically stable state were randomized to aripiprazole or standard-of-care antipsychotics. The Clinical Global Impression (CGI), Positive and Negative Syndrome Scale, and Investigator's Assessment Questionnaire were used monthly. The Udvalg for Kliniske Undersogelser side-effect rating scale scores and treatment emergent adverse events were recorded to assess the safety and tolerability of switching to aripiprazole from other antipsychotics. A total of 292 patients were randomly assigned to receive aripiprazole (N = 245) or non-aripiprazole antipsychotics (N = 47). Mean CGI-Improvement score at 12 weeks was 3.56+/-1.29 (95% confidence interval: 3.39-3.73) in the aripiprazole group, indicating that aripiprazole was effective in treating schizophrenic patients. Aripiprazole treatment resulted in improvement from baseline on all efficacy outcome measures, including Positive and Negative Syndrome Scale total, positive, negative, and general subscale, and CGI-Severity scores. In addition, after aripiprazole treatment, the remission rate was increased from 43.9% at baseline to 51.7% at 12 weeks. The proportion of patients with symptom worsening at 12 weeks was low (12.4%). Both Investigator's Assessment Questionnaire and Udvalg for Kliniske Undersogelser scores showed that there were fewer prolactin-related adverse events in the aripiprazole group than in the standard-of-care antipsychotics group (P<0.05). There were no significant between-group differences in time to failure to maintain remission and time to dropout. In the naturalistic setting, symptomatically stable outpatients with schizophrenia who were switched to aripiprazole showed clinically meaningful treatment benefits. The majority of patients was successfully switched from other antipsychotics without serious symptom exacerbation or adverse events over a course of 12 weeks.

Brexpiprazole has a low risk of dopamine D2 receptor sensitization and inhibits rebound phenomena related to D2 and serotonin 5‐HT2A receptors in rats

“…Therefore, olanzapine at 3 mg/kg is a side effect dose. Accumulating evidence shows that switching to aripiprazole may provide favorable outcomes by potentially improving psychosis and by decreasing metabolic problems such as weight gain . However, aripiprazole may transiently worsen psychosis in some cases after an abrupt discontinuation of a prior atypical antipsychotic drug .…”

Effects of paliperidone extended release on the symptoms and functioning of schizophrenia

“…The results demonstrated an improvement in symptomatic remission rate after the 12-week treatment of paliperidone ER. Another study showed that the remission rate was increased from 43.9% at baseline to 51.7% at 12 weeks after aripiprazole treatment [29]. The original RSWG criteria requires 6 month duration, we have not used the criteria for remission as originally defined.…”

Dopamine supersensitivity psychosis and dopamine partial agonist: A retrospective survey of failure of switching to aripiprazole in schizophrenia

“…These switching failures were speculated to be attributable to its unique receptor profile of DPA ( Takeuchi et al., 2009 ). Indeed several ARI trials suggested that a switching method of concomitant ARI initiation and tapering off of the current medication could cause a relapse of psychosis ( Lin et al., 2009 ; Pae et al., 2009 ), although this result was not always confirmed in other trials ( Casey et al., 2003 ; Kim et al., 2009 ). In addition, Pae and colleagues noticed a possible association between psychotic relapse following switching to ARI and DSP ( Pae, 2009 ; Pae et al., 2010 ).…”