A Randomized Controlled Trial of Long-Acting Injectable Risperidone vs Continuation on Oral Atypical Antipsychotics for First-Episode Schizophrenia Patients: Initial Adherence Outcome
Center for Cognitive Medicine, Department of Psychiatry, University of Illinois, Chicago, IL 60612, USA. The Journal of Clinical Psychiatry
(Impact Factor: 5.5).
10/2009; 70(10):1397-406. DOI: 10.4088/JCP.09m05284yel
Nonadherence for first-episode schizophrenia is a major unsolved challenge. The long-acting injectable route is an appealing strategy, but there are concerns about acceptability. We report on acceptance and initial adherence outcomes with risperidone long-acting injection (RLAI) in first-episode schizophrenia patients.
We conducted a prospective randomized controlled trial in which we enrolled patients defined by appropriate Structured Clinical Interview for DSM-IV diagnosis and < or = 16 weeks of lifetime antipsychotic exposure. Participants were randomly assigned (2:1 ratio) to a recommendation of changing to RLAI versus continuing on oral therapy (ORAL). Nonadherence behavior was defined as a medication gap > or = 14 days. Adherence attitudes were determined by the Rating of Medication Influences (ROMI) scale. A priori analysis defined treatment groups as intent-to-treat (ITT) and as-actually-treated (AAT) for the first 12 weeks after initial randomization. Participants were enrolled from December 2004 to March 2007.
Of 46 eligible patients, 37 were randomly assigned, 11 to ORAL and 26 to RLAI. Nineteen of 26 patients (73%) accepted the RLAI recommendation. There were no differences in adherence behavior at 12 weeks based on initial randomization (Kaplan-Meier survival for ITT: 76% [95% CI, 35%-90%] adherent for RLAI vs 72% [95% CI, 55%-89%] for ORAL; log-rank P = .78), but patients accepting RLAI were significantly more likely to be adherent than patients staying on ORAL (AAT: 89% [95% CI, 64%-97%] adherent for RLAI vs 59% [95% CI, 32%-78%] for ORAL; log-rank P = .035). There were no ROMI attitude differences between either treatment group comparison at 12 weeks.
Most first-episode patients taking oral antipsychotics will accept a recommendation of RLAI therapy. On the basis of initial randomization status, an RLAI recommendation did not affect adherence behavior at 12 weeks. However, acceptance of RLAI was associated with significantly better adherence. Regardless of whether RLAI is recommended or accepted, there is no adverse impact on subsequent medication attitudes at 12 weeks. These results support the feasibility and acceptability of introducing RLAI as a treatment option for first-episode schizophrenia patients.
clinicaltrials.gov Identifier: NCT00220714.
Available from: Martin Lambert
- "Additional benefits in the RLAI treated patients included greater reduction in the total Positive and Negative Syndrome Scale (PANSS) (10% vs. 2%; p = 0.001), and in the Clinical Global Impression-Severity (CGI-S) scale (10% vs. 2.5%; p = 0.001) and greater functional improvement as measured by the General Assessment of Functioning (GAF) scale, with patients on RLAI showing an increase of 26% while patients on oral risperidone experienced a 0.5% improvement (p = 0.001). A prospective randomised controlled study specifically compared medication adherence during continuation treatment in first-episode patients (with ≤16 weeks of lifetime total antipsychotic medication exposure) following stabilization with oral risperidone . Eleven patients received continuation treatment with oral risperidone while twenty-six were treated with RLAI. "
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ABSTRACT: The use of long-acting injectable antipsychotics (LAIs) in schizophrenia is usually restricted to patients in long-term treatment, who prefer them to oral antipsychotics, and to patients with multiple relapses who have a history of non-adherence. However, preliminary evidence from patients in the early phases of the disease suggest that second generation LAIs may be superior to second generation oral medications with regard to the control of negative symptoms and psychosocial functioning. Moreover, several studies have found that psychiatrists are generally reluctant to prescribe LAI antipsychotics and under-estimate their acceptability by patients. Key elements to take into account when offering a LAI in the early course of schizophrenia should include their potential superiority in allowing early detection of non-adherence and in reducing the number of rehospitalisations and relapses.
Copyright © 2014 Elsevier Masson SAS. All rights reserved. Published by Elsevier Masson SAS. All rights reserved.
Available from: Nina R Schooler
- "Explanatory Pragmatic Study objectives To determine efficacy and safety in a controlled environment To determine efficacy and safety in a real-world clinical en- vironment Population selection Specific selection criteria may not be fully representative of the population requiring treatment; extensive exclusion criteria Includes all patients who meet basic inclusion criteria; minimal exclusion criteria Site selection Experienced practitioners in an optimal controlled clinical environment Sites are selected broadly from relevant settings that provide treatment to the target population Intervention during trial Limited flexibility; changes in randomized treatment may end study participation Highly flexible; participants retained in treatment even after change of randomized assignment Outcome measures Primary measures are often not applicable to a real-world situation (e.g., use of rating systems or scales not used in routine clinical practice) Include objective measures pertinent to clinicians, patients, and public health officials Adherence Maximized to allow accuracy in analysis of efficacy and safety Allowed to reflect a real-world clinical environment Randomization Random assignment to treatment Often incorporate randomization; completely nonrandomized trials introduce selection bias of an injection allow a definitive assessment of adherence to LAI medications, but adherence to oral treatments can only be determined by less definitive methods. These include self report, pharmacy data, clinical records, family report, pill counts (manual or electronic), or serum medication levels (Valenstein et al., 2002; Weiden et al., 2009; Rosenheck et al., 2011). "
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ABSTRACT: This article reviews key methodological considerations for clinical trials that utilize explanatory and pragmatic trial designs and relates these contrasting approaches to the interpretation of results from comparisons of oral versus long-acting injectable (LAI) antipsychotics in schizophrenia. Explanatory randomized controlled trials (RCTs) generally measure the efficacy of a treatment in a homogeneous population with intensive, frequent, and often clinical trial-specific assessments. In contrast, pragmatic trials measure effectiveness in routine clinical practice and frequently aim to inform choices between treatments. Comparative effectiveness outcomes with pragmatic designs in naturalistic settings for schizophrenia treatments are of increasing interest to healthcare providers because outcomes of treatment (both efficacy and safety) may vary significantly when identified in an explanatory setting compared with a naturalistic pragmatic setting. Indeed, it has been suggested that the inconsistent outcomes observed in trials comparing oral and LAI antipsychotic medications may be a function of the use of explanatory or pragmatic trial designs.
In practice, clinical trial designs are seldom purely explanatory or pragmatic. To identify the predominant orientation of a trial, one must consider multiple features. This paper reviews the relative impact of these features when comparing LAI and oral antipsychotic treatments and makes recommendations for improving these comparative designs.
Available from: Florence Thibaut
- "In fi rst-episode schizophrenia patients, long-acting injectable risperidone was well tolerated and led to more treatment adherence than oral risperidone in a prospective RCT (Weiden et al. 2009). Another longterm 2-year open-label study with fi rst-episode schizophrenia patients revealed that 64% of the patients achieved remission and that 97% of the patients maintained this status until study completion (Emsley et al. 2008). "
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ABSTRACT: Abstract Objectives. This article presents an overview of the current literature on biological markers for alcoholism, including markers associated with the pharmacological effects of alcohol and markers related to the clinical course and treatment of alcohol-related problems. Many of these studies are well known, while other studies cited are new and still being evaluated. Methods. In this paper we first describe known biomarkers of alcohol-related disorders, review their features and the problems involved in their use. We then consider future developments on biomarkers and their possible impact on the field. Results. More recent findings cited include the work on type 7 adenylcyclase (AC) polymorphism and its lower expression levels in female alcoholics. Neuroimaging studies involving biomarkers have also reported brain volume reductions of gray and white matter, including amygdala and subcortical regions in alcoholic patients, while a high association between the copy number variations (CNVs) in 6q14.1/5q13.2 and alcohol dependence has more recently been identified in genetic studies. Conclusions. In addition to their possible importance for diagnosis, biomarkers may have utility for predicting prognosis, progression of the disorder, the development of new treatments, and monitoring treatment effects. Although such findings should be verified in independent studies, the search for new biomarkers is continuing. Several potential candidate biomarkers have been found recently in blood, imaging, and genetic studies with encouraging results.
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