Riad Dirani

Effectiveness of injectable risperidone long-acting therapy for schizophrenia: data from the US, Spain, Australia, and Belgium

BackgroundBecause wide variations in mental health care utilization exist throughout the world, determining long-term effectiveness of psychotropic medications in a real-world setting would be beneficial to physicians and patients. The purpose of this analysis was to describe the effectiveness of injectable risperidone long-acting therapy (RLAT) for schizophrenia across countries.MethodsThis was a pragmatic analysis of data from two prospective observational studies conducted in the US (Schizophrenia Outcomes Utilization Relapse and Clinical Evaluation [SOURCE]; ClinicalTrials.gov registration number for the SOURCE study: NCT00246194) and Spain, Australia, and Belgium (electronic Schizophrenia Treatment Adherence Registry [eSTAR]). Two separate analyses were performed to assess clinical improvement during the study and estimate psychiatric hospitalization rates before and after RLAT initiation. Clinical improvement was evaluated using the Clinical Global Impressions-Severity (CGI-S) and Global Assessment of Functioning (GAF) scales, and change from baseline was evaluated using paired t tests. Psychiatric hospitalization rates were analyzed using incidence densities, and the bootstrap resampling method was used to examine differences between the pre-baseline and post-baseline periods.ResultsThe initial sample comprised 3,069 patients (US, n = 532; Spain, n = 1,345; Australia, n = 784; and Belgium, n = 408). In all, 24 months of study participation, completed by 39.3% (n = 209), 62.7% (n = 843), 45.8% (n = 359), and 64.2% (n = 262) of patients from the US, Spain, Australia, and Belgium, respectively, were included in the clinical analysis. Improvements compared with baseline were observed on both clinical assessments across countries (P < 0.001 at all post-baseline visits). The mean improvement was approximately 1 point on the CGI-S and 15 points on the GAF. A total of 435 (81.8%), 1,339 (99.6%), 734 (93.6%), and 393 (96.3%) patients from the US, Spain, Australia, and Belgium, respectively, had ≥1 post-baseline visit and were included in the analysis of psychiatric hospitalization rates. Hospitalization rates decreased significantly in all countries regardless of hospitalization status at RLAT initiation (P < 0.0001) and decreased significantly in the US and Spain (P < 0.0001) when the analysis was limited to outpatients only.ConclusionsRLAT in patients with schizophrenia was associated with improvements in clinical and functional outcomes and decreased hospitalization rates in the US, Spain, Australia, and Belgium, despite differences in health care delivery systems.

Psychometric evaluation of the Medication Satisfaction Questionnaire (MSQ) to assess satisfaction with antipsychotic medication among schizophrenia patients

The Medication Satisfaction Questionnaire (MSQ) is a single-item questionnaire which evaluates satisfaction with antipsychotic medication in schizophrenia patients. This study evaluated the reliability and validity for its use in research and clinical settings. Data pooled across treatment groups (control vs. Paliperidone ER) from a randomized 6-week study were used to conduct four psychometric assessments of the MSQ: (1) test-retest reliability, (2) convergent validity, (3) known-groups validity, and (4) minimally important difference (MID). This analysis included 191 randomized subjects. Test-retest reliability was evaluated for patients with no change in satisfaction from weeks 2 to 4 and weeks 4 to 6 (ICC=0.80; 0.83, respectively). Convergent validity was demonstrated through large correlations with Treatment Satisfaction Questionnaire for Medication (TSQM) global score (r=0.72-0.77), and through small correlations with variables measuring clinical symptoms and functioning (e.g., Positive and Negative Syndrome Scale (PANSS) total score [r=-0.30 to -0.17], CGI-S [r=-0.35 to -0.27], SF-36 Physical Functioning Score [r=0.18] and side effects and extrapiramidal measures (including UKU, ESRS-A, SAS). Mean MSQ scores were significantly different between those who completed and discontinued the study, and between different satisfaction groups based on TSQM, demonstrating good known-groups validity. MID estimates for the MSQ ranged from 0.47 (standard error of measurement) to 0.58 (anchor-based method). Results suggest that the MSQ has acceptable reliability and validity, making this single-item questionnaire appropriate and easy to use in clinical research and potentially in clinical practice. A 1-point change on the MSQ may be considered clinically meaningful.

Changes in schizophrenia-related hospitalization and ER use among patients receiving paliperidone palmitate: results from a clinical trial with a 52-week open-label extension (OLE)

Abstract Background: Schizophrenia affects ∼1.1% of the United States population, resulting in substantial direct, indirect and societal costs. Objective: To evaluate hospitalization rates associated with use of paliperidone palmitate (PP). Methods: Data were from a variable-duration double-blind (DB), randomized, relapse-prevention comparison (NCT00111189) of PP vs. placebo (Pbo), followed by a 1-year open-label extension (OLE). Between-phase change in schizophrenia-related hospitalizations was evaluated using data from an investigator-completed questionnaire. Change in hospitalizations using patients before enrollment who participated in the OLE phase was also analyzed. Poisson regression was used to evaluate changes in incidence density within exposure category and by schizophrenia duration. Results: A total of 160 patients in the PP-PP group and 153 in the Pbo-PP group from the DB to the OLE phase were included. Mean age (standard deviation [SD]), gender, and duration of schizophrenia were similar at the start of the DB phase (Pbo: 38.5 years [10.6], 51.0% male, 68.0% ≥5 years’ duration; PP: 37.3 years [11.4] (p = 0.342); 51.9% male (p = 0.874); 70.0% ≥5 years’ duration (p = 0.698), respectively. From the DB to the end of the OLE phase, the number of hospitalizations per person-year for patients treated during the DB phase with Pbo significantly declined from 0.27 to 0.06 (78% reduction; p = 0.005). A statistically nonsignificant difference was observed for PP patients treated during the DB phase with PP (0.11–0.04; 63.6% reduction; p = 0.076), compared with the OLE phase. Change from before enrollment to the end of the OLE phase (n = 381) produced similar results (0.35–0.04; 88.6% reduction; p < 0.001). Patients who enroll in a clinical trial may be different from the general population and this may affect the generalizability of results. Conclusion: From the double-blind to the open-label phase and from prior to the trial until the end of the open-label phase, hospitalizations significantly decreased for patients with schizophrenia treated with PP.

Hospitalisation and resource utilisation in patients with schizophrenia following initiation of risperidone long-acting therapy in the Veterans Affairs Healthcare System

Abstract Objective: To examine hospitalisation rates and resource utilisation following initiation of risperidone long-acting therapy (RLAT) among US veterans with schizophrenia. Methods: Encounter data were analysed from the Ohio Veterans Affairs (VA) Healthcare System. Adult patients (schizophrenia or schizoaffective disorder) with ≥1 medical or hospital visits with a diagnosis code of 295.xx, continuous enrolment from January 2003 through January 2006, and ≥4 injections of RLAT were selected. Analyses compared psychiatric-related resource utilisation pre- and post-exposure to RLAT; each patient served as his/her own control. The pre-exposure and post-exposure periods defined were equal in duration (e.g., a 6-month post-exposure period was matched with a 6-month pre-exposure period). Descriptive and comparative analyses (paired t tests, McNemars test) were performed. Results: Patients (n=106) were 51.9 years old (±10.2), male (93%), white (73%) and received on average 14 RLAT doses (±9.7; range, 4–47 injections) over 309 days (±196; range, 42–737 days). Most experienced a psychiatric-related hospitalisation prior to initiation; less than half experienced hospitalisation after initiation (75% vs. 42%; p<0.001). Relative to pre-initiation, fewer psychiatric-related hospitalisations (mean [SD] change, –0.8 [2.0]; p<0.001), shorter length of stay (–25 [63.6] days; p<0.001), fewer inpatient days/month (–3.1 [7.2] days) and one (2.8) additional outpatient visit/month (p<0.001) occurred post-initiation. Limitations: The absence of a control group in this pre-/post comparison may have resulted in exposure to a regression to the mean effect. Also, this study evaluated only one cohort of patients in a VA healthcare setting. Conclusions: VA patients with schizophrenia and schizoaffective disorder treated with RLAT experienced fewer hospitalisations and psychiatric-related inpatient days following RLAT initiation. Further studies utilising a control group and in non-VA populations are warranted.

One-year clinical and economic consequences of oral atypical antipsychotics in the treatment of schizophrenia*

ABSTRACT Objective: To assess the clinical and economic consequences of oral atypical antipsychotic treatment (aripiprazole, olanzapine, paliperidone ER, quetiapine, risperidone, and ziprasidone) in schizophrenia over one-year from a US healthcare system perspective. Methods: The decision model captured rates of discontinuation, symptom response, frequency and duration of relapse, adverse events (extrapyramidal symptoms and weight gain), resource utilization, and unit costs. Published randomized, double-blind, placebo-controlled clinical trial data were used to obtain response rates for comparators. Published clinical trial data from long-term effectiveness trials reflective of typical clinical settings were used for time on therapy, rates of discontinuation, likelihood of switching, relapse rates, and adverse event rates. Drug costs were based on Wholesale Acquisition Cost weighted by Wolters Kluwer Retail and First Databank Pricing drug utilization data. PharMetrics Patient-Centric database was utilized for length of stay, frequency of relapse, and unit cost of healthcare resource data. A clinical expert panel provided resource-use information not available in published literature or healthcare databases. To test the robustness of the findings, sensitivity analyses were performed using plausible ranges of key model input parameters. Results: The model estimated that, over 1 year, clinical outcomes of patients administered oral atypical antipsychotics would not vary considerably. This is partly due to differences ‘washing out’ because of frequent switching and discontinuation of medication. Economic outcomes did vary among pharmacotherapies: paliperidone ER was associated with cost savings in direct medical costs per patient per year compared to risperidone (cost savings using paliperidone ER vs. risperidone:

Systematic review of long-acting injectables versus oral atypical antipsychotics on hospitalization in schizophrenia

793), quetiapine (

Prevalence of liver disease in veterans with bipolar disorder or schizophrenia

1191), olanzapine (

Predicting hospital admission and discharge with symptom or function scores in patients with schizophrenia: pooled analysis of a clinical trial extension

1259), ziprasidone (

Workplace productivity, employment issues, and resource utilization in patients with bipolar I disorder.

2159), and aripiprazole (

Association between adherence to and persistence with atypical antipsychotics and psychiatric relapse among US Medicaid-enrolled patients with schizophrenia

2204)). Limitations of this analysis include the absence of direct head-to-head long-term comparative data for antipsychotics. However, the results of the decision analysis held true when tested through a multitude of sensitivity analyses. Conclusion: This modeling study showed that paliperidone ER had the most favorable clinical and economic outcomes compared to other oral atypical antipsychotics for patients with schizophrenia. The analysis supports the notion that frequent discontinuation of medication is a problem with all oral antipsychotic treatments for schizophrenia.