Correction to: A phase III randomized trial of gantenerumab in prodromal Alzheimer's disease.

Following publication of the original article [1], the author reported errors in the formatting of the table. The details of the errors are as follows.

A phase III randomized trial of gantenerumab in prodromal Alzheimer's disease.

BACKGROUND: Gantenerumab is a fully human monoclonal antibody that binds aggregated amyloid-ß (Aß) and removes Aß plaques by Fc receptor-mediated phagocytosis. In the SCarlet RoAD trial, we assessed the efficacy and safety of gantenerumab in prodromal Alzheimer's disease (AD). METHODS: In this randomized, double-blind, placebo-controlled phase III study, we investigated gantenerumab over 2 years. Patients were randomized to gantenerumab 105 mg or 225 mg or placebo every 4 weeks by subcutaneous injection. The primary endpoint was the change from baseline to week 104 in Clinical Dementia Rating Sum of Boxes (CDR-SB) score. We evaluated treatment effects on cerebrospinal fluid biomarkers (all patients) and amyloid positron emission tomography (substudy). A futility analysis was performed once 50% of patients completed 2 years of treatment. Safety was assessed in patients who received at least one dose. RESULTS: Of the 3089 patients screened, 797 were randomized. The study was halted early for futility; dosing was discontinued; and the study was unblinded. No differences between groups in the primary (least squares mean [95% CI] CDR-SB change from baseline 1.60 [1.28, 1.91], 1.69 [1.37, 2.01], and 1.73 [1.42, 2.04] for placebo, gantenerumab 105 mg, and gantenerumab 225 mg, respectively) or secondary clinical endpoints were observed. The incidence of generally asymptomatic amyloid-related imaging abnormalities increased in a dose- and APOE ε4 genotype-dependent manner. Exploratory analyses suggested a dose-dependent drug effect on clinical and biomarker endpoints. CONCLUSIONS: The study was stopped early for futility, but dose-dependent effects observed in exploratory analyses on select clinical and biomarker endpoints suggest that higher dosing with gantenerumab may be necessary to achieve clinical efficacy. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01224106 . Registered on October 14, 2010.

ADHD Symptom Rebound and Emotional Lability With Lisdexamfetamine Dimesylate in Children Aged 6 to 12 Years.

OBJECTIVE: To describe symptom rebound in children with ADHD treated with lisdexamfetamine dimesylate (LDX) or placebo. METHOD: During a 4-week, randomized, double-blind, placebo-controlled trial of LDX, parents/caregivers completed the Conners' Parent Rating Scale-Revised: Short Form symptom rating scale throughout the day. Response, rebound, and emotional lability (EL) were assessed post hoc based on predefined criteria. RESULTS: Most participants given LDX ( n = 207) were responders throughout the day (50.7%-55.6%) versus placebo ( n = 72; 11.1%-22.2%). A total of seven (3.4%) LDX participants showed rebound in the afternoon and/or evening versus seven (9.7%) with placebo. In both groups, most incidences of rebound occurred in the evening. EL (mean) was higher in LDX rebounders and nonresponders (range = 4.2-9.0) versus LDX responders (range = 1.3-1.6) and versus placebo rebounders (range = 0.7-1.9). CONCLUSION: ADHD symptom rebound occurred in few participants (3.3%) given LDX (accompanied by clinically significant EL). Overall, more participants given LDX versus placebo responded throughout the day.

Lisdexamfetamine dimesylate in adults with attention-deficit/ hyperactivity disorder who report clinically significant impairment in executive function: results from a randomized, double-blind, placebo-controlled study.

OBJECTIVE: Behavioral rating scales that assess impairments in executive function commonly associated with attention-deficit/hyperactivity disorder (ADHD) may offer advantages over neuropsychological testing. The primary objective of this study was to evaluate the efficacy of lisdexamfetamine dimesylate for executive function deficits in adults with ADHD and clinically significant executive function impairment using self-reported Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A) assessments. METHOD: This randomized double-blind study, conducted between May 2010 and November 2010, screened at least 1 participant at 35 of 39 registered US clinical research sites. Adults (aged 18-55 years) with a primary ADHD diagnosis (meeting full DSM-IV-TR criteria) and executive function deficits (assessed by baseline BRIEF-A Global Executive Composite [GEC] T-scores of at least 65) were randomized to treatment with optimized lisdexamfetamine dimesylate (30 mg/d, 50 mg/d, or 70 mg/d; n = 80) or placebo (n = 81) during a 10-week double-blind treatment period. Outcome measures included the BRIEF-A scales (GEC, index, and clinical subscales). RESULTS: At week 10 or at early termination, lisdexamfetamine dimesylate was associated with significantly greater reductions from baseline in mean BRIEF-A GEC T-scores than placebo (effect size, 0.74; P < .0001) and significantly greater reductions from baseline in mean T-scores for both BRIEF-A index scales (Behavioral Regulation Index and Metacognition Index) and all 9 clinical subscales (P ≤ .0056 for all). At week 10 or at early termination, mean T-scores for BRIEF-A indexes and clinical subscales were below levels of clinically significant executive function deficits (ie, < 65) with lisdexamfetamine dimesylate treatment. The mean (SD) GEC T-score was 57.2 (14.11) for the lisdexamfetamine dimesylate group and 68.3 (17.12) for the placebo group. The safety profile of lisdexamfetamine dimesylate was consistent with other long-acting psychostimulants. CONCLUSION: Among adults with ADHD and clinically significant executive function deficits, lisdexamfetamine dimesylate was associated with significant improvements in self-reported executive function ratings. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01101022.

Adjunctive lisdexamfetamine dimesylate therapy in adult outpatients with predominant negative symptoms of schizophrenia: open-label and randomized-withdrawal phases.

Negative symptoms of schizophrenia (NSS), related to hypodopaminergic activity in the mesocortical pathway and prefrontal cortex, are predictive of poor outcomes and have no effective treatment. Use of dopamine-enhancing drugs (eg, psychostimulants) has been limited by potential adverse effects. This multicenter study examined lisdexamfetamine dimesylate (LDX), a d-amphetamine prodrug, as adjunctive therapy to antipsychotics in adults with clinically stable schizophrenia and predominant NSS. Outpatients with stable schizophrenia, predominant NSS, limited positive symptoms, and maintained on stable atypical antipsychotic therapy underwent a 3-week screening, 10-week open-label adjunctive LDX (20-70 mg/day), and 4-week, double-blind, randomized, placebo-controlled withdrawal. Efficacy measures included a modified Scale for the Assessment of Negative Symptoms (SANS-18) and Positive and Negative Syndrome Scale (PANSS) total and subscale scores. Ninety-two participants received open-label LDX; 69 received double-blind therapy with placebo (n=35) or LDX (n=34). At week 10 (last observation carried forward; last open-label visit), mean (95% confidence interval) change in SANS-18 scores was -12.9 (-15.0, -10.8; P<0.0001). At week 10, 52.9% of participants demonstrated a minimum of 20% reduction from baseline in SANS-18 score. Open-label LDX was also associated with significant improvement in PANSS total and subscale scores. During the double-blind/randomized-withdrawal phase, no significant differences (change from randomization baseline) were found between placebo and LDX in SANS-18 or PANSS subscale scores. In adults with clinically stable schizophrenia, open-label LDX appeared to be associated with significant improvements in negative symptoms without positive symptom worsening. Abrupt LDX discontinuation was not associated with positive or negative symptom worsening. Confirmation with larger controlled trials is warranted.

Lifespan persistence of ADHD: the life transition model and its application.

BACKGROUND: The understanding that attention-deficit/hyperactivity disorder (ADHD) often persists throughout life has heightened interest of patients, families, advocates, and professionals in a longitudinal approach to management. Such an approach must recognize and address known patient- and systems-based challenges of long-term mental health treatment, shifting of clinical presentations of ADHD, and commonality of psychiatric comorbidity with ADHD. OBJECTIVE: The ADHD Life Transition Model is a step toward developing criteria to optimize recognition and clinical management of ADHD (eg, response, remission) across an individual's lifespan and across diverse medical subspecialties. To support therapeutic efficiency and adaptability, our proposed model highlights periods when external resources for managing ADHD are reduced, cognitive and behavioral stressors are increased, and individuals may be reevaluating how they perceive, accept, and adhere to ADHD treatment. Such a model aims to support the clinical community by placing in context new findings, which suggest that the prevention of adult psychopathology in individuals with pediatric ADHD may be possible. CONCLUSIONS: The ADHD Life Transition Model seeks to improve care for individuals with ADHD by (1) underscoring that ADHD persists beyond childhood in at least two-thirds of patients, (2) raising awareness of the need to approach ADHD from a chronic illness standpoint, and (3) increasing mental health professionals' diligence in symptom recognition and management of ADHD across developmental phases from childhood through adulthood.

Managing ADHD across the lifespan in the primary care setting.

Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurobehavioral condition that affects most patients throughout their lives and is associated with occupational underachievement, psychiatric comorbidity, and substance abuse. Primary care physicians (PCPs) are at the forefront of helping patients with ADHD manage symptoms and overcome functional impairments. In this article, the problems of recognizing and effectively managing ADHD are explored through the presentation of 2 composite patient cases based on real patients in the authors' practices. Both cases highlight maturational changes in ADHD-related problems as patients develop through childhood, adolescence, and into adulthood. The striking differences between the cases serve to illustrate the highly varied clinical presentation and developmental trajectories of ADHD, moderated by family environment, patient characteristics, and life events. Emphasis is placed on understanding the crucial developmental turning points from early childhood through adulthood at which patients with ADHD are most likely to need increased support and specialized behavioral interventions. Diagnosis of adult ADHD is also reviewed, including an overview of potentially clinically relevant patient characteristics that should alert PCPs to the possible presence of ADHD and use of the World Health Organization's rapid 6-item adult ADHD Self-Report Scale as a screening device. The present discussion challenges PCPs to recognize the varied presentations of what ADHD "looks like," and describes the need for PCPs to establish and maintain working partnerships with families, patients, and mental health care professionals in their local communities to successfully treat ADHD across the lifespan.

A New Psychosocial Tool for Gaining Patient Understanding and Acceptance of Long-acting Injectable Antipsychotic Therapy.

Nonadherence to antipsychotic medications in serious, persistent mental illness remains a significant clinical challenge. Long-acting therapy was developed to help improve adherence to schizophrenia therapy and provide an effective means for ameliorating symptoms and preventing relapse. The Agency for Health Care Policy and Research/National Institute of Mental Health Schizophrenia Patient Outcomes Research Team recommends that antipsychotic long-acting therapy be strongly considered for patients who have difficulty adhering to an oral medication regimen or who prefer long-acting therapy. Depot conventional formulations have long been available; for clinicians and patients who would rather use an atypical antipsychotic, studies with risperidone long-acting therapy suggest that it is efficacious and well tolerated. A common concern of clinicians who elect to initiate long-acting therapy is how to introduce the possibility of changing from the current oral antipsychotic to an long-acting therapy injection. As with other aspects of patient care, having an established therapeutic relationship with the patient is advantageous for recommending changes in care, but the way in which the idea is approached may improve the likelihood of its acceptance. To help clinicians broach a recommendation of long-acting therapy with their patients, the GAIN approach was designed as a standard interview process for presenting this option. It encompasses (and is an acronym for) goal setting, action planning, initiating treatment, and nurturing motivation. This novel clinical tool is based on the principles of motivational enhancement therapy, a patient-centered approach that seeks to evoke the patient's own motivation for change, to consolidate the decision to change, and to plan for change. This tool is also based on the Listen-Empathize-Agree-Partner, or LEAP, communication strategy. Motivational enhancement therapy, which is typically brief, has been found effective in several chronic illnesses in both outpatient and inpatient settings. GAIN may be a practical tool for aligning clinician-patient expectations and enhancing long-term maintenance of therapy.

Remission in schizophrenia: applying recent consensus criteria to refine the concept.

Although the concept of remission has been widely accepted and utilized in depression and anxiety disorders, there has been much less emphasis on defining remission in schizophrenia. Recently, an expert consensus definition of remission in schizophrenia was proposed along specific operational criteria for the attainment of remission focusing on the three core dimensions of psychopathology identified within schizophrenia: psychoticism, disorganization and negative symptoms. To date, the criteria have been applied retrospectively to several clinical studies, and these have demonstrated that the proposed definition of remission correlates significantly with established measures of symptom severity, functioning and quality of life, and appears achievable for a significant proportion of patients receiving at least 3 months of pharmacotherapy. In this article we extend the notion of remission to include an examination of the possible association of several modifiable and unmodifiable factors and co-morbidities on remission status. We also propose an investigation into the likelihood of different patient populations in achieving remission as well as assessing the impact of remission on health care costs and family burden. Since cognitive dysfunction and negative symptoms may be strongly correlated with a lower likelihood of achieving remission, we recommend retrospective and/or prospective studies to determine the relationship between neurocognitive status and the predominance of negative symptoms at treatment start and the probability of achieving remission. Taken together, these studies should help identify key predictors of remission, further define the remitted state, reduce therapeutic pessimism, raise treatment expectations and chart a strategy for further research in this important area.

Long-acting risperidone in young adults with early schizophrenia or schizoaffective illness.

BACKGROUND: Treatment with long-acting injectable risperidone was evaluated in young adults likely to be in the early stages of schizophrenia or schizoaffective disorder. METHOD: An open-label 50-week trial included young adults (men aged 18-25 years and women aged 18-30 years). RESULTS: Sixty-six young adults received at least 1 injection of long-acting risperidone (25 or 50 mg) every two weeks; 64% of the patients completed the 50-week trial. A mode dose of 25 mg/14 days was received by 23 patients and 50 mg/14 days by 43 patients. Mean PANSS scores improved significantly from baseline at each time point, with 64% of the patients showing clinical improvement (>or=20% reduction in PANSS total scores) at endpoint. Patient-rated quality of life (SF-36 scores) improved and patients' attitudes toward the medication were positive (DAI scores). Severity of movement disorders (ESRS) and injection-site pain ratings were low throughout the trial. Results were similar in the population of other (older) patients. CONCLUSIONS: Long-acting risperidone was associated with clinical benefits in stable young adults with early schizophrenia or schizoaffective illness.

Evaluation of a treatment manual for risperidone long-acting injectable.

We evaluated the usefulness of a treatment manual to facilitate the use of long-acting injectable risperidone in community mental health centers (CMHCs) during an open-label observational study. Perceived clinical utility and clinician adherence to the manual were evaluated. Patient adherence to treatment satisfaction, Clinical Global Impression of Severity (CGI-S) and the Schizophrenia Quality-of-Life Scale (SQLS) were assessed. Mean score for overall utility of the guidebook was 4.2 +/- .6 (scale ratings ranged from 1 = not at all to 5 = extremely). Most clinicians (89-100%) found the guidebook useful, and were adherent to key aspects of appropriate treatment use including concomitant oral risperidone use and injection and dosing parameters for long-acting risperidone. Most patients were adherent to treatment (86.7%), preferred long-acting risperidone over oral risperidone (72.6%) or other oral antipsychotics (78.4%) and were satisfied with long-acting risperidone (90.1%). The open-label observational design limits interpretation of these data. However, in this study manual-supported use of long-acting risperidone was associated with successful implementation of this pharmacologic treatment in the CMHC setting.

Maintenance therapy with once-monthly administration of long-acting injectable risperidone in patients with schizophrenia or schizoaffective disorder: a pilot study of an extended dosing interval.

BACKGROUND: Several clinical studies have established the efficacy, safety, and tolerability of long-acting risperidone administered once every 2 weeks in patients with schizophrenia or schizoaffective disorder. This report evaluates preliminary efficacy, safety, tolerability, and pharmacokinetic data for a novel (once-monthly) administration of long-acting injectable risperidone 50 mg in patients with schizophrenia or schizoaffective disorder. METHODS: Clinically stable patients participated in a 1-year, open-label, single-arm, multicenter pilot study. During the 4-week lead-in phase, patients received long-acting risperidone 50 mg injections every 2 weeks, with 2 weeks of oral risperidone supplementation. Injections of long-acting risperidone 50 mg every 4 weeks followed for up to 48 weeks, without oral supplementation. The primary endpoint was relapse; other assessments included PANSS, CGI-S, adverse event reports, and determination of risperidone and 9-hydroxyrisperidone plasma concentrations. RESULTS: Twelve patients in the intent-to-treat population (n = 67) met relapse criteria (17.9%). Relapse risk at 1 year was estimated as 22.4%. Non-statistically significant improvements in symptoms (PANSS) and clinical status (CGI-S) at endpoint were observed. The most common adverse events included schizophrenia aggravated not otherwise specified (19.5%), anxiety (16.1%), insomnia (16.1%), and headache (11.5%). There were no unexpected safety and tolerability findings. Mean plasma concentrations for risperidone and 9-hydroxyrisperidone were generally stable during the study. CONCLUSION: Once-monthly dosing of long-acting risperidone was well tolerated, associated with a relatively low relapse rate (similar to that reported with other antipsychotics), and maintained the clinically stable baseline status of most patients. Although the results suggest that some symptomatically stable patients with schizophrenia or schizoaffective disorder might be safely managed with long-acting risperidone 50 mg once monthly, these findings alone do not identify which patients will have a sufficient therapeutic benefit nor do they quantify comparative effects of standard and altered dosing. Study limitations (the open-label pilot study design, small sample size, and lack of a concurrent biweekly treatment arm) prevent broad interpretations and extrapolations of results. Controlled studies would be required to support a recommendation for alternative dosing regimens.

A 1-year double-blind study of 2 doses of long-acting risperidone in stable patients with schizophrenia or schizoaffective disorder.

OBJECTIVE: This study examined the effects of 2 doses of long-acting risperidone injection in patients with schizophrenia or schizoaffective disorder. METHOD: This 52-week, prospective, randomized, double-blind, multicenter, international study included clinically stable outpatients with schizophrenia or schizoaffective disorder (DSM-IV criteria). Settings included physicians' offices and clinics. Patients received a fixed dose of long-acting risperidone (25 or 50 mg) every 2 weeks. Primary outcome was time to relapse, defined as either re-hospitalization or other exacerbation criteria. Other assessments included the Positive and Negative Syndrome Scale, Clinical Global Impressions-Severity of Illness scale, and functional and quality-of-life measures. Safety was assessed via treatment-emergent adverse events, laboratory tests, and movement disorder rating scales. Data were collected from December 2002 to September 2004. RESULTS: A total of 324 patients were randomized to 25 mg (N = 163) or 50 mg (N = 161) of long-acting risperidone. Time to relapse was comparable (p = .131) for both groups. Projected median time to relapse was 161.8 weeks (95% CI = 103.0 to 254.2) with 25 mg and 259.0 weeks (95% CI = 153.6 to 436.8) with 50 mg. One-year incidences of relapse were 21.6% (N = 35) and 14.9% (N = 24), respectively (p = .059). Psychiatric hospitalization was the reason for relapse for 16 (10%) in the 25-mg group and 10 (6%) in the 50-mg group. Patients experienced statistically significant but modest improvements at endpoint in most measures (i.e., psychotic symptoms, functioning, movement disorder severity) with both doses, with no significant between-group differences. CONCLUSION: In this 1-year study, long-acting risperidone was associated with low relapse and rehospitalization rates, indicating that doses of 25 to 50 mg are appropriate for long-term treatment in schizophrenia.

Effects of risperidone augmentation in patients with treatment-resistant depression: Results of open-label treatment followed by double-blind continuation.

Approximately one-third of persons with depression do not respond to antidepressant monotherapy. Studies suggest that atypical antipsychotic augmentation may benefit these patients. We investigated the longer-term efficacy of risperidone augmentation of serotonin-selective reuptake inhibitor treatment for resistant depression. In 57 in- and outpatient centers in three countries, we conducted a three-phase study with 4-6 weeks of open-label citalopram monotherapy, 4-6 weeks of open-label risperidone augmentation, and a 24-week double-blind, placebo-controlled discontinuation phase. A total of 489 patients with major depressive disorder and 1-3 documented treatment failures entered the citalopram monotherapy phase (20-60 mg/day). Patients with <50% reduction in HAM-D-17 scores entered the risperidone augmentation phase (0.25-2.0 mg/day). Patients with HAM-D-17< or =7 or CGI-S < or = 2 were randomized to risperidone or placebo augmentation. The primary outcome was time to relapse during the double-blind phase. During citalopram monotherapy, 434 patients had <50% HAM-D-17 reduction; 299 (68.9%) were fully nonresponsive (<25% reduction) and 135 were partially nonresponsive (25-49% reduction). Of the 386 nonresponders who entered the augmentation phase, 243 remitted and 241 entered the double-blind phase. Median time to relapse was 102 days with risperidone augmentation and 85 days with placebo (NS); relapse rates were 53.3 and 54.6%, respectively. In a post hoc analysis of patients fully nonresponsive to citalopram monotherapy, median time to relapse was 97 days with risperidone augmentation and 56 with placebo (p = 0.05); relapse rates were 56.1 and 64.1%, respectively (p < or = 0.05). Open-label risperidone augmentation substantially enhanced response in treatment-resistant patients, but the longer-term benefits of augmentation were not demonstrated in this study.

Insight and its relationship to clinical outcomes in patients with schizophrenia or schizoaffective disorder receiving long-acting risperidone.

Poor insight is common in schizophrenia, predictive of non-compliance, and an impediment to effective patient management. We hypothesized that long-acting risperidone would be associated with enhanced insight, contributing to improved quality of life measures. In an international, open-label 50-week study, stable patients received long-acting risperidone every 2 weeks. Assessments included the Positive and Negative Syndrome Scale [PANSS; item G12 rated 'impaired insight and judgment' from 1 (no impairment) to 7 (severe impairment)]; Clinical Global Impressions-Severity (CGI-S); and the Medical Outcomes Study Short-form 36-item Health Survey (SF-36) (patient-rated quality of life). Correlation and regression post-hoc analyses examined associations between insight and other measures. At baseline, 314 (51.1%; N=614) patients had impaired insight (G12=3-7) and 83 (26.4%) achieved normal or near normal ratings at endpoint (G12=1-2). Symptom severity corresponded with insight: baseline mean+/-SD PANSS total scores were 56.0+/-14.4 in patients without impaired insight (G12=1-2); 73.4+/-15.7 with mild-moderate impairment (G12=3-4); and 86.0+/-17.4 with severe impairment (G12=5-7). These scores improved significantly in each group at endpoint (P<0.001). Improved insight ratings correlated with improvements in CGI-S (r=0.37); PANSS disorganized thought (r=0.46); negative symptoms (r=0.32); and anxiety/depression (r=0.24; P<0.001 all comparisons), but not quality of life ratings. The change in insight did not contribute significantly to the variance in SF-36 scores; however, changes in negative symptoms, anxiety/depression and CGI-S scores did contribute significantly. Long-acting risperidone was associated with improvements in insight, symptom domains, clinical status and quality of life measures. Associations were noted between patient-rated quality of life and specific symptom domains, but not insight.

Lack of impact of race on the efficacy and safety of long-acting risperidone versus placebo in patients with schizophrenia or schizoaffective disorder.

This analysis aimed to assess the relationship between race and clinical response to long-acting, injectable risperidone treatment in patients with schizophrenia or schizoaffective disorder. In a 12-week, randomized, double-blind study, patients with schizophrenia or schizoaffective disorder received placebo or long-acting risperidone (25, 50 or 75 mg every 2 weeks). Data were stratified by race as identified by demographic information: Caucasian, African-American or Other. Psychotic symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS); movement disorders by the Extrapyramidal Symptom Rating Scale (ESRS); adverse events (AEs) were reported spontaneously. Data were available for 439 patients: 193 Caucasian (44%), 174 (40%) African-American and 72 (16%) Other patients. Baseline characteristics were similar between racial groups, as were study completion rates (overall: 30% placebo; 48% long-acting risperidone). There was a significant effect of treatment (P<0.001), but not of race, on improvement in PANSS total scores from baseline to endpoint. ESRS scores were low throughout the study, and no significant impact of race was observed. Overall rates of AEs were similar among the racial groups. Race did not appear to impact the efficacy and tolerability of long-acting risperidone.

An assessment of emergent tardive dyskinesia and existing dyskinesia in patients receiving long-acting, injectable risperidone: results from a long-term study.

INTRODUCTION: Treatment-emergent tardive dyskinesia (TD) can be a serious side effect of antipsychotic treatment. Atypical antipsychotics are associated with a lower risk for TD than are conventional agents. A long-acting atypical antipsychotic, with more stable blood levels and lower peak blood levels than an oral formulation, may provide differential benefit regarding side effects, including movement disorders. This analysis assessed TD by defined research criteria in patients receiving long-acting, injectable risperidone. METHODS: Clinically stable subjects with schizophrenia or schizoaffective disorder participated in a 50-week, open-label trial of long-acting, injectable risperidone. TD was studied by defined research criteria (Schooler, N.R., Kane, J.M., 1982. Research diagnosis for tardive dyskinesia. Arch. Gen. Psychiatry. 39, 486-487; Americal Psychiatric Association, 2000. Diagnostic and Statistical Manual of Mental Disorders, fourth ed. American Psychiatric Association, Washington, DC). The severity of dyskinesia and other movement disorders were rated by the Extrapyramidal Symptom Rating Scale (ESRS). RESULTS: ESRS dyskinesia data were available for 662 patients. Five of 530 subjects without dyskinesia at baseline (0.94%) met the predefined criteria for emergent persistent TD during therapy. Based on either exposure to study medication or Kaplan-Meier analysis, the 1-year rate was 1.19%. Among the 132 subjects with dyskinesia at baseline, the mean score on the ESRS physician's exam for dyskinesia improved significantly at endpoint (-2.77; P<0.0001), regardless of anticholinergic drug use. (P=0.243 for patients with versus without anticholinergic drug use.) CONCLUSIONS: In this open-label study, treatment with long-acting risperidone was associated with a low rate of emergent persistent TD. Significant improvement in existing dyskinesias was noted. The TD rate reported here is consistent with other reports of atypical antipsychotics and substantially lower than with conventional antipsychotics.

Abnormal Involuntary Movement Scale (AIMS) and Extrapyramidal Symptom Rating Scale (ESRS): cross-scale comparison in assessing tardive dyskinesia.

Assessing tardive dyskinesia (TD) has been complicated by the use of different research criteria and rating scales. We studied concordance between two commonly used scales, the Abnormal Involuntary Movement Scale (AIMS) and Extrapyramidal Symptom Rating Scale (ESRS), to study interscale concordance and criteria to define TD. Patients with schizophrenia or schizoaffective disorder (N = 374) were rated at baseline with both scales. Linear and logistic regression models explored relationships between scale ratings and mapped scores for corresponding items. TD was defined as at least mild in > or = 2 anatomical areas, or moderate or greater symptoms in > or = 1 area at baseline. Logistic regression was used to find simplified criteria for predicting AIMS-defined TD by ESRS scores. There was a strong association on corresponding item ratings. "Mild" was defined as AIMS score of 2 and ESRS 2 or 3, and "moderate or greater" as AIMS score > or = 3 and ESRS > or = 4. Using these criteria, there was 96.0% (359/374) agreement between AIMS- and ESRS-defined TD cases. The ESRS Clinical Global Impressions of severity of dyskinesia (CGI-SD) best predicted AIMS-defined TD. An ESRS CGI-SD > or = 4 (95% CI: 3.61, 4.76) was associated with > or = 95% probability of AIMS-defined TD. High concordance between the scales for dyskinesia scores was found. Findings suggest that the ESRS CGI-SD score can serve as a simplified criterion for identifying AIMS-defined TD, and may be a useful tool for future research-based TD analyses, when occurring in the context of a full movement disorder assessment.