Patricia K. Corey-Lisle

Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder

OBJECTIVE: The objective of this study was to evaluate short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder who were manifesting behaviors such as tantrums, aggression, self-injurious behavior, or a combination of these. METHODS: This 8-week, double-blind, randomized, placebo-controlled, parallel-group study was conducted of children and adolescents (aged 6–17 years) with autistic disorder. Patients were randomly assigned (1:1) to flexibly dosed aripiprazole (target dosage: 5, 10, or 15 mg/day) or placebo. Efficacy outcome measures included the Aberrant Behavior Checklist irritability subscale and the Clinical Global Impression–Improvement score (CGI-I). Safety and tolerability were also assessed. RESULTS: Ninety-eight patients were randomly assigned to receive placebo (n = 51) or aripiprazole (n = 47). Mean improvement in Aberrant Behavior Checklist irritability subscale score was significantly greater with aripiprazole than with placebo from week 1 through week 8. Aripiprazole demonstrated significantly greater global improvements than placebo, as assessed by the mean CGI-I score from week 1 through week 8; however, clinically significant residual symptoms may still persist for some patients. Discontinuation rates as a result of adverse events (AEs) were 10.6% for aripiprazole and 5.9% for placebo. Extrapyramidal symptom-related AE rates were 14.9% for aripiprazole and 8.0% for placebo. No serious AEs were reported. Mean weight gain was 2.0 kg on aripiprazole and 0.8 kg on placebo at week 8. CONCLUSIONS: Aripiprazole was efficacious in children and adolescents with irritability associated with autistic disorder and was generally safe and well tolerated.

Economic Implications of Treatment-Resistant Depression Among Employees

AbstractBackground: Conservative estimates indicate between 10% and 20% of all individuals with major depressive disorders (MDDs) fail to respond to conventional antidepressant therapies. Amongst those with MDD, individuals with treatment-resistant depression (TRD) have been found to be frequent users of healthcare services and to incur significantly greater costs than those without TRD. Given the prevalence of the disorder, it is understandable that MDDs are responsible for a significant amount of both direct and indirect healthcare costs. Objective: To provide empirical findings for employees likely to have TRD based on analysis of employer claims data, in the context of previous research. Methods: We conducted a claims data analysis of employees of a large national (US) employer. The data source consisted of medical, pharmaceutical and disability claims from a Fortune 100 manufacturer for the years 1996–1998 (total beneficiaries <100 000). The employee sample included individuals with medical or disability claims for MDDs (n = 1692). A treatment pattern algorithm was applied to classify MDD patients into TRD-likely (n = 180) and TRD-unlikely groups. Treated prevalence of select comorbid conditions and the patient costs (direct and indirect) from the employer perspective by condition were compared among TRD-likely and TRD-unlikely employees, and with a 10% random sample of the overall employee population for 1998. Results: The average annual cost of employees considered TRD-likely was

Impact of Obesity on Health-related Quality of Life in Schizophrenia and Bipolar Disorder

US14 490 per employee, while the cost for depressed but TRD-unlikely employees was

Remission, response without remission, and nonresponse in major depressive disorder: impact on functioning

US6665 per employee, and

Risk of diabetes mellitus associated with atypical antipsychotic use among Medicaid patients with bipolar disorder: a nested case-control study.

US4043 for the employee from the random sample. TRD beneficiaries used more than twice as many medical services compared with TRD-unlikely patients, and incurred significantly greater work loss costs. Conclusion: TRD has gained increasing recognition due to both the clinical challenges and economic burdens associated with the condition. TRD imposes a significant economic burden on an employer. TRD-likely employees are more likely to be treated for selected comorbid conditions and have higher medical and work loss costs across all conditions.

Naturalistic Impact of Second-Generation Antipsychotics on Weight Gain

Objective: Studies have reported that up to 60% of individuals with schizophrenia and 68% of those with bipolar disorder are overweight/obese. This paper explores the health‐related quality of life (HRQOL) of individuals with schizophrenia or bipolar disorder as a function of obesity status.

Validation of the Investigator's Assessment Questionnaire, a new clinical tool for relative assessment of response to antipsychotics in patients with schizophrenia and schizoaffective disorder

Major depressive disorder (MDD) is associated with significant functional impairment. This post-hoc analysis of data from two randomized trials assessed the impact of response status on functioning in MDD. Patients with at least one historical treatment failure followed by an inadequate response after 8 weeks of prospective open-label treatment with escitalopram, fluoxetine, paroxetine-CR, sertraline, or venlafaxine-XR plus single-blind placebo were randomized to 6 weeks of double-blind treatment with adjunctive placebo or adjunctive aripiprazole. At the end of double-blind treatment, patients were defined as: in remission [≥50% reduction in Montgomery–Åsberg Depression Rating Scale (MADRS) score with MADRS ≤10]; with a response without remission (≥50% reduction in MADRS with MADRS >10); or with a nonresponse (all others). Functional status was assessed with the Sheehan Disability Scale. Of the 679 patients, 144 were in remission, 44 had a response without remission, and 491 had a nonresponse. Mean improvements in the Sheehan Disability Scale total and item scores were significantly greater in patients in remission versus those with a response without remission (P<0.02) as well as nonresponse (P<0.001). Structural Equation Modeling found that efficacy (Hamilton Rating Scale for Depression scores) did not significantly correlate with functioning in this study. In conclusion, MDD patients achieving symptomatic remission experience greater functional improvements than those respond without remission. Functioning may be a distinctly different outcome from symptom reduction. Treatments focused on producing high remission rates may improve patient functioning over and above that seen with patients who only achieve response.

Changes in weight and weight-related quality of life in a multicentre, randomized trial of aripiprazole versus standard of care

Study Objective. To quantify the risk of diabetes mellitus associated with atypical antipsychotics compared with conventional antipsychotics in managed care Medicaid patients with bipolar disorder.

Q‐TWiST analysis of ixabepilone in combination with capecitabine on quality of life in patients with metastatic breast cancer

Background: While second-generation antipsychotics (SGAs) have had benefits over earlier antipsychotic treatments, their use has been associated with reports of weight gain. Body mass index (BMI) has been studied in clinical trials with limited comparison between drugs. Objective: To investigate the impact of each SGA on the risk of weight increase in an adult population. Methods: Using a national electronic medical records database, a naturalistic impact of SGAs on BMI was evaluated. Patients (aged ≥ 18 y) receiving a prescription for an antipsychotic drug between January 1995 and March 2004 were identified. An adverse event was defined as at least a 7% increase in BMI from baseline within one year of antipsychotic prescription and a post-increase BMI of at least 25 kg/m2. Results: A total of 9394 patients were identified, with 1514 cases of increased BMI after initial prescription. Risperidone (OR 1.39; 95% CI 1.16 to 1.66), quetiapine (OR 1.36; 95% CI 1.13 to 1.64), and olanzapine (OR 1.76; 95% CI 1.50 to 2.07)were significantly more likely to cause BMI increase compared with first-generation antipsychotics (FGAs). Aripiprazole (OR 0.72; 95% CI 0.36 to 1.46), ziprasidone (OR 0.68; 95% CI 0.39 to 1.18), and clozapine (OR 1.01; 95% CI 0.56 to 1.81) were less likely to induce weight gain compared with FGAs. Conclusions: This study provides a foundation for understanding how SGAs impact weight gain in a naturalistic, as opposed to a clinical trial, setting and provides evidence that there are differential risks of weight gain between SGAs. Because of negative long-term health effects of weight gain, physicians need to take all factors into consideration when recommending pharmaceutical therapy for patients with severe mental illness.

M1810 The Impact of Hepatitis-C Viral (HCV) Treatment On Work Absence and Productivity

The success of long-term therapy in schizophrenia is contingent upon real-world effectiveness or improvements in several domains, including efficacy, safety and tolerability. This report describes the Investigators Assessment Questionnaire (IAQ), a new 10-item instrument designed to assess relative effectiveness (efficacy, safety and tolerability) of antipsychotic medications in patients with schizophrenia or schizoaffective disorder. To measure content validity, 300 psychiatrists rated the importance of the IAQ items. Efficacy (i.e., positive and negative symptoms) was considered most important, but importance scores relative to the mean ranged only from 0.87 to 1.18, suggesting similar importance of the items. Cronbachs coefficient alpha values showed that the items were internally consistent. Factor analyses indicated that all IAQ items belong to a single domain. Data from the US Broad Effectiveness Trial of Aripiprazole were used for construct validation. Total IAQ score correlated significantly with time to treatment discontinuation (r=-0.50), Clinical Global Impressions-Improvement (CGI-I) score (r=0.76) and medication preference of patients (r=0.71) or caregivers (r=0.70). A one-unit decrease in IAQ score corresponded to an additional 1.35 days in the study and a decrease in CGI-I of 0.21 units. These results provide initial validation of the IAQ as a tool for evaluating antipsychotic response in patients with schizophrenia or schizoaffective disorder.