Clozapine is associated with significant weight gain and metabolic disturbances. This multicentre, randomized study comprised a double-blind, placebo-controlled treatment phase of 16 wk, and an open-label extension phase of 12 wk. Outpatients who met DSM-IV-TR criteria for schizophrenia, who were not optimally controlled while on stable dosage of clozapine for > or =3 months and had experienced weight gain of > or =2.5 kg while taking clozapine, were randomized (n=207) to aripiprazole at 5-15 mg/d or placebo, in addition to a stable dose of clozapine. The primary endpoint was mean change from baseline in body weight at week 16 (last observation carried forward). Secondary endpoints included clinical efficacy, body mass index (BMI) and waist circumference. A statistically significant difference in weight loss was reported for aripiprazole vs. placebo (-2.53 kg vs. -0.38 kg, respectively, difference=-2.15 kg, p<0.001). Aripiprazole-treated patients also showed BMI (median reduction 0.8 kg/m(2)) and waist circumference reduction (median reduction 2.0 cm) vs. placebo (no change in either parameter, p<0.001 and p=0.001, respectively). Aripiprazole-treated patients had significantly greater reductions in total and low-density lipoprotein (LDL) cholesterol. There were no significant differences in Positive and Negative Syndrome Scale total score changes between groups but Clinical Global Impression Improvement and Investigator's Assessment Questionnaire scores favoured aripiprazole over placebo. Safety and tolerability were generally comparable between groups. Combining aripiprazole and clozapine resulted in significant weight, BMI and fasting cholesterol benefits to patients suboptimally treated with clozapine. Improvements may reduce metabolic risk factors associated with clozapine treatment.

Findings from PK data, PK simulations, and clinical studies all support that 400 mg is the appropriate initiation dose of AOM for patients with schizophrenia. When switching to oral aripiprazole before initiating AOM 400, tapering the prior oral antipsychotic while titrating up the oral aripiprazole dose (target dose 10-30 mg/d) over >1 to 4 weeks may be an effective strategy. The efficacy, safety, and tolerability of AOM 400 were comparable regardless of whether patients were previously stabilized on oral aripiprazole 10 or 30 mg/d or other antipsychotic therapy and continued to receive the same oral antipsychotic for the first 14 days after initiating AOM 400.

IntroductionTwo risk minimization (RM) tools—a healthcare professional frequently asked questions (HCP-FAQs) brochure and a patient/caregiver information brochure (PCIB)—were developed for HCPs and for adolescents (aged ≥ 13 years) receiving aripiprazole for bipolar I mania and their caregivers.ObjectivesThis study evaluated the effectiveness of these RM tools in improving the awareness and education of HCPs and patients/caregivers.MethodThe RM tools were distributed to HCPs (identified in agreement with the marketing authorization holder [MAH] and local regulatory authorities), who in turn distributed the PCIBs to patients/caregivers. A web-based survey was then conducted targeting HCPs and patients/caregivers.ResultsThe response rate was low: 118 of 23,282 invited HCPs and 16 patients/caregivers completed the survey. Overall, 42% (49/118) of HCP respondents were aware of aripiprazole RM tools; of these, 59% (29/49) of HCPs read them at least once and 66% (19/29) of these used the RM tools while discussing the benefit–risk profile of aripiprazole with patients/caregivers. In total, 30 of the 118 HCPs (25%) were aware of the PCIB, and 26 distributed it to their patients/caregivers, whereas seven HCPs advised them to read the brochure. Overall, 15 of the 16 patients/caregivers were aware of the PCIB, and 13 read/referred to it. Of these, 12 found the PCIB useful, and five monitored their weight while receiving aripiprazole and reported potential risks immediately to their HCP.ConclusionThe response rate to the survey was low, and the tools displayed limited utility and effectiveness in improving awareness and education in a small number of responders. Therefore, the aripiprazole risk management plan was amended, and the tools were discontinued.Electronic supplementary materialThe online version of this article (10.1007/s40264-018-0662-2) contains supplementary material, which is available to authorized users.

To determine the Minimal Clinically Important Difference (MCID) of the Heinrichs-Carpenter Quality of Life Scale (QLS). Data from the "Schizophrenia Trial of Aripiprazole" (STAR) study were used in this analysis. The MCID value of the QLS total score was estimated using the anchor-based method. These findings were substantiated/validated by comparing the MCID estimate to other measurements collected in the study. Half of the patients (49%) showed improvement in Clinical Global Impressions of Severity (CGI-S) during the trial. The estimated MCID of the QLS total score was 5.30 (standard error: 2.60; 95% confidence interval: [0.16; 10.43]; p < 0.05). Patients were divided into two groups: "QLS improvers" (QLS total score increased ≥ six points) and "non-improvers". The QLS improvers had significantly better effectiveness and reported significantly higher levels of preference for their current medications. There was a statistically significant difference between the two groups in the change in two of the four domains of QLS; "Interpersonal relations" and "Intrapsychic foundations" domains during the study. These findings support the value of the estimated MCID for the QLS and may be a useful tool in evaluating antipsychotic treatment effects and improving long-term patient outcomes in schizophrenia. Copyright © 2015 John Wiley & Sons, Ltd.

Background and Aim:Significant weight increase in schizophrenic patients can impact on compliance and is associated with long-term cardiovascular complications. This study aims to evaluate the effect on weight, overall efficacy, safety and tolerability of combining aripiprazole and clozapine in schizophrenic patients with suboptimal response to clozapine.Methods:This 16-week, multicentre, randomised, double-blind, placebo-controlled study included patients with schizophrenia (DSM-IV-TR) experiencing at least 2.5 kg weight gain and suboptimal efficacy and/or safety on clozapine. Patients were randomised to a combination of aripiprazole (5-15 mg/day) and clozapine or clozapine monotherapy (baseline dose maintained up to 16 weeks). Endpoints included body weight change from baseline to Week 16 (primary), PANSS, CGI-I, IAQ scales, and safety assessments (secondary).Results:Two hundred and seven patients were randomised (baseline mean weight = 92.4 kg [52-148.4], mean weight gain on clozapine = +14.9 kg [2.5-66], mean clozapine dose = 373.7 mg/d), and 90% and 94% completed the study for combination and monotherapy, respectively. Statistically significant reductions from baseline were observed in both mean body weight (-2.53 kg and -0.38 kg, p<0.001) and waist line (-0.00 cm and -2.00 cm, p<0.001) on combination compared with monotherapy. BMI, fasting total and LDL cholesterol, and CGI-I and IAQ significantly improved on combination. There was no change in PANSS total score. Five patients discontinued for adverse events on combination, and one patient on monotherapy.Conclusion:Although there was no benefit regarding psychopathological symptoms, combining aripiprazole and clozapine results in significant benefits in terms of weight, BMI and fasting cholesterol in schizophrenic patients suboptimally treated with clozapine monotherapy.