Healthcare Provider Engagement with a Novel Dashboard for Tracking Medication Ingestion: Impact on Treatment Decisions and Clinical Assessments for Adults with Schizophrenia.

Purpose: Schizophrenia is a severe, chronic condition accounting for disproportionate healthcare utilization. Antipsychotics can reduce relapse rates, but the characteristics of schizophrenia may hinder medication adherence. A phase 3b open-label clinical trial used aripiprazole tablets with sensor (AS; includes pills with ingestible event-marker, wearable sensor patches and smartphone application) in adults with schizophrenia. This post hoc analysis explored how healthcare providers' (HCPs) usage of a dashboard that provided medication ingestion information impacted treatment decisions and clinical assessments. Patients and Methods: Participants used AS for 3-6 months. HCPs were instructed to check the dashboard regularly, identify features used, and report impact on treatment decisions. After stratifying HCPs by frequency of dashboard checks and resulting treatment decisions, changes from baseline were calculated for Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI)-Severity of Illness and CGI-Improvement (CGI-I), and Personal and Social Performance (PSP), and compared using Mann-Whitney U-tests and rank-biserial correlation coefficient (r) effect sizes. Results: To ensure sufficient opportunity for AS engagement, 113 participants who completed ≥3 months on study were analyzed. HCPs most often accessed dashboard data regarding medication ingestion and missed doses. HCPs recommended adherence counseling and participant education most often. Participants whose HCPs used the dashboard more and recommended adherence counseling and participant education (n=61) improved significantly more than participants with less dashboard-active HCPs (n=49) in CGI-I mean score (2.9 versus 3.4 [p=0.004]), total PANSS (mean change: -9.2 versus -3.1 [p=0.0002]), PANSS positive subscale (-3.2 versus -1.5 [p=0.003]), PANSS general subscale (-4.3 versus -1.2 [p=0.02]), and Marder factor for negative symptoms (-1.9 versus 0.0 [p=0.03]). Most HCPs found the dashboard easy to use (74%) and helpful for improving conversations with participants about their treatment plan and progress (78%). Conclusion: This provider dashboard may facilitate discussions with patients about regular medication-taking, which can improve patient outcomes.

Pharmacokinetics and safety of deltoid or gluteal injection of aripiprazole lauroxil NanoCrystal® Dispersion used for initiation of the long-acting antipsychotic aripiprazole lauroxil.

BACKGROUND: Aripiprazole lauroxil (AL), a long-acting injectable antipsychotic for the treatment of schizophrenia in adults, can be started with either 21 days of daily oral aripiprazole supplementation or a 1-day initiation regimen consisting of a single injection of a NanoCrystal® Dispersion formulation of AL (ALNCD) and a single dose of 30 mg oral aripiprazole. This phase I study assessed the pharmacokinetics and safety of deltoid versus gluteal ALNCD injections. METHODS: Patients with schizophrenia or schizoaffective disorder (N = 47) were randomized 1:1 to receive a single intramuscular dose of ALNCD in the deltoid or gluteal muscle. Plasma samples were collected over 85 days to measure ALNCD concentration by injection site. Relative aripiprazole bioavailability for deltoid versus gluteal injection was assessed based on area under the curve (AUC∞ and AUClast) and maximum concentration (Cmax) values. Adverse events were monitored throughout the study. RESULTS: Plasma aripiprazole concentrations after a single ALNCD injection were comparable between deltoid and gluteal administration. Mean maximum plasma aripiprazole concentrations were 196.1 ng/ml (deltoid) and 175.0 ng/ml (gluteal). Exposure to aripiprazole was similar, with mean AUC∞ values of 6591 day × ng/ml for deltoid and 6437 day × ng/ml for gluteal. Aripiprazole bioavailability was not significantly different between injection sites. ALNCD administration in the deltoid or gluteal muscle was well tolerated, with similar safety profiles at both sites. CONCLUSION: ALNCD demonstrated similar exposure and safety profiles between the two administration sites, suggesting that ALNCD can be given in either the gluteal or the deltoid muscles as a component of the 1-day initiation regimen for AL.

Evaluation of functionally meaningful measures for clinical trials of cognition enhancement in schizophrenia.

OBJECTIVE: Because reduction of psychotic symptoms in schizophrenia does not result in adequate community functioning, efforts have shifted to other areas, such as cognitive impairment. The U.S. Food and Drug Administration requires that drugs for cognition enhancement in schizophrenia show improvement on two distinct outcome measures in clinical trials: an accepted cognitive performance battery and a functionally meaningful coprimary measure. The authors examined the reliability, validity, and practicality of functionally meaningful measures. METHOD: In this four-site validation study, schizophrenia patients were assessed at baseline (N=166) and 4 weeks later (N=144) on performance-based (Independent Living Scales, Test of Adaptive Behavior in Schizophrenia [TABS], and UCSD Performance-based Skills Assessment [UPSA]) and interview-based (Cognitive Assessment Interview and Clinical Global Impression Scale for Cognition) candidate coprimary measures. In addition, cognitive performance, community functioning, and clinical symptoms were assessed. Both full and short forms of the performance-based measures were evaluated. RESULTS: All measures were well tolerated by patients, had adequate test-retest reliability, and showed good utility as a repeated measure. Measures differed in their correlation with cognitive performance, with performance-based measures having stronger correlations than interview-based measures. None of the measures had notable floor or ceiling effects or missing data. CONCLUSIONS: Among the full-form measures, the UPSA was judged to have the strongest overall properties. Among the short forms, the TABS and UPSA appeared to have the strongest features. Use of the short forms saves time, but at the cost of lower test-retest reliability and weaker correlations with cognitive performance.

A novel, point-of-care test for lithium levels: description and reliability.

BACKGROUND: Lithium is a highly effective agent for numerous psychiatric disorders but requires therapeutic monitoring because of its narrow therapeutic index. This article describes a novel instant blood test that will facilitate the routine monitoring process. METHOD: This instant blood test allows the clinician to take a finger-stick sample of whole blood and determine the plasma lithium level in a 2-minute period. This new test is compared with standard laboratory measurements for lithium in human subjects. The reliability of the new test is reported as agreement with standard laboratory values in 3 studies involving a total of 269 subjects. RESULTS: The test demonstrates extremely high reliability (r = 0.962, 0.928, 0.983 for studies 1-3, respectively) for the measurement of serum and plasma lithium levels as compared with standard laboratory measures. CONCLUSION: This new test is reliable and offers unique advantages over standard laboratory procedures for measuring lithium levels in patients.

Oxcarbazepine versus Divalproex Sodium for the Continuing Treatment of Mania.

BACKGROUND AND OBJECTIVE: Oxcarbazepine, an antiepileptic and a derivative of carbamazepine, has been shown to have clinical utility as an antimanic agent. This study sought to assess the efficacy and tolerability of oxcarbazepine compared with divalproex sodium in the treatment of patients with mania. PATIENTS AND METHODS: 57 patients from a large clinical practice who had recently begun treatment with divalproex sodium were randomly assigned to one of two treatment groups. In this open-label, single (rater)-blind study, group 1 remained on treatment with divalproex sodium and group 2 was switched to oxcarbazepine. Both treatment groups were followed for 10 weeks after the switch. Pharmacotherapeutic efficacy was compared using the Clinician Administered Rating Scale for Mania (CARS-M). Weight and adverse events were monitored throughout the study. RESULTS: 83% of patients using oxcarbazepine showed a decrease in mania as assessed using the CARS-M, and 70% showed a net decrease in weight over the 10-week course of the study. For the divalproex sodium group, 53% showed a decrease in mania, as assessed by CARS-M, and 37% lost weight. CONCLUSION: Oxcarbazepine showed comparable efficacy to divalproex sodium, yet appeared to do so with an equal or more benign side-effect profile, particularly with regard to weight. These results suggest that oxcarbazepine, which has been used in Europe for the treatment of mood disorders for some time (albeit used off-label for this purpose) may show promise for use in the US as an agent for maintenance of non-acute mania.