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A Randomized Trial of Iloperidone for Prevention of Relapse in Schizophrenia: The REPRIEVE Study.

ABSTRACT: The purpose of this study was to evaluate the safety and effectiveness of iloperidone for the prevention of relapse in schizophrenia.Study subjects were adults with schizophrenia who started on oral open-label iloperidone titrated to an initial target dose of 12 mg/day (6 mg twice daily) and then stabilized on a flexible-dose iloperidone regimen (range 8-24 mg/day) for up to 24 weeks. Subjects meeting stabilization criteria then entered the relapse-prevention phase and were randomized 1:1 in a double-blind fashion to continue with iloperidone or placebo withdrawal for up to 26 weeks or until meeting relapse or other withdrawal criteria.A total of 303 subjects were randomized to the relapse-prevention phase; 153 continued to receive iloperidone, and 150 were withdrawn to placebo. The modal total daily dose for iloperidone in all phases of the study was 12 mg/day. The pre-defined unblinded interim analysis upon reaching 68 relapse events confirmed the hypothesis that iloperidone (n = 97) was more effective than placebo (n = 96) in preventing relapse events, and the trial was stopped early. The estimated relapse rates were 63.4 % (Kaplan-Meier [KM] estimate) for placebo compared with 20.4 % (KM estimate) for those continuing to receive iloperidone (log rank test: p < 0.0001). The mean time to relapse was 71 days for placebo and 139 days for iloperidone (hazard ratio 4.7; 95 % confidence interval 2.7-8.3; p < 0.0001). The safety profile observed in previous short-term studies was also reaffirmed in this maintenance treatment setting. The most common treatment-emergent adverse events (TEAEs) in the stabilization phase were dizziness (11.6 %), somnolence (8.3 %), and dry mouth (6.8 %). Rates of reported extrapyramidal disorder or akathisia during stabilization were 2.5 and 3.7 %, respectively.Flexible dosing of iloperidone for maintenance-phase therapy, with a modal dose of 12 mg/day was effective in preventing relapse in subjects previously stabilized on iloperidone. The adverse event profile for iloperidone was consistent with other studies, and the low extrapyramidal symptom and akathisia burden during stabilization was sustained during the course of the study. ClinicalTrials.gov identifier: NCT01291511.

SUBMITTER: Weiden PJ

PROVIDER: S-EPMC4982888 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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A Randomized Trial of Iloperidone for Prevention of Relapse in Schizophrenia: The REPRIEVE Study.

Weiden Peter J PJ Manning Raymond R Wolfgang Curt D CD Ryan J Michael JM Mancione Linda L Han Guangyang G Ahmed Saeed S Mayo Mallery G MG

CNS drugs 20160801 8

<h4>Background</h4>The purpose of this study was to evaluate the safety and effectiveness of iloperidone for the prevention of relapse in schizophrenia.<h4>Methods</h4>Study subjects were adults with schizophrenia who started on oral open-label iloperidone titrated to an initial target dose of 12 mg/day (6 mg twice daily) and then stabilized on a flexible-dose iloperidone regimen (range 8-24 mg/day) for up to 24 weeks. Subjects meeting stabilization criteria then entered the relapse-prevention p ...[more]

PMID: 27379654

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Project description:Abstract Background: Relapse is common in schizophrenia; identifying characteristics associated with relapse may help improve disease management. Cariprazine, a D3/D2 receptor partial agonist, is approved in the United States for the treatment of schizophrenia. Post hoc analyses of a long-term, randomized, double-blind (up to 72 weeks), relapse prevention trial (NCT01412060) were performed to identify characteristics associated with relapse in placebo- and cariprazine-treated patients. Methods: Baseline characteristics in cariprazine-treated (3, 6, or 9?mg/d) or placebo-treated patients were evaluated in relation to relapse status. Demographic variables included age, sex, race, weight, and BMI. Psychiatric history variables included mean age at illness onset, duration of schizophrenia, duration of current episode, number of lifetime psychotic episodes, previous hospitalizations, and acute exacerbations in the past year. Baseline rating scale severity scores (eg, Positive and Negative Syndrome Scale [PANSS] and Clinical Global Impressions-Severity [CGI-S]) were evaluated. Differences in demographic and psychiatric history variables were evaluated using the Student t test (categorical variables) or Fisher exact test (continuous variables); rating scale severity scores were evaluated with 2-way ANOVA with relapse and study center as factors. Results: Relapse occurred in nearly twice as many placebo-treated (47.5%) as cariprazine-treated patients (24.8%) (hazard ratio [95% CI] = 0.45 [0.28, 0.73]). For cariprazine-treated patients who relapsed vs those who did not, significant differences were seen in baseline age (mean, 43 vs 38 y), weight (85 vs 73?kg), BMI (29 vs 26?kg/m2), and race (all, P < .05); for placebo-treated patients, there were no significant differences in demographic variables based on relapse status. In both treatment groups, patients who relapsed vs patients who did not relapse had a greater mean number of previous hospitalizations (cariprazine = 8.4 vs 4.3 [P = .0199]; placebo = 4.9 vs 2.8 [P = .0183]). Cariprazine patients who relapsed vs those who did not had longer illness duration (18.1 y vs 9.9 [P = .0005]); the number of lifetime episodes also differed by relapse status (P = .0016), with a greater percentage of relapsed patients experiencing ?5 episodes. Baseline PANSS total score and CGI-S scores were not significantly different in relapsed vs nonrelapsed patients in either treatment group. Conclusion: While patients treated with cariprazine had a lower rate of relapse than placebo overall, the results suggest that patients who were older, heavier, or had a later stage of illness may be more prone to relapse during cariprazine treatment. In patients randomized to placebo, demographic characteristics and psychiatric history were not as meaningful in predicting relapse. Greater symptom severity at baseline did not appear to be associated with relapse.

Project description:IMPORTANCE:Relapse is highly prevalent following substance abuse treatments, highlighting the need for improved aftercare interventions. Mindfulness-based relapse prevention (MBRP), a group-based psychosocial aftercare, integrates evidence-based practices from mindfulness-based interventions and cognitive-behavioral relapse prevention (RP) approaches. OBJECTIVE:To evaluate the long-term efficacy of MBRP in reducing relapse compared with RP and treatment as usual (TAU [12-step programming and psychoeducation]) during a 12-month follow-up period. DESIGN, SETTING, AND PARTICIPANTS:Between October 2009 and July 2012, a total of 286 eligible individuals who successfully completed initial treatment for substance use disorders at a private, nonprofit treatment facility were randomized to MBRP, RP, or TAU aftercare and monitored for 12 months. Participants medically cleared for continuing care were aged 18 to 70 years; 71.5% were male and 42.1% were of ethnic/racial minority. INTERVENTIONS:Participants were randomly assigned to 8 weekly group sessions of MBRP, cognitive-behavioral RP, or TAU. MAIN OUTCOMES AND MEASURES:Primary outcomes included relapse to drug use and heavy drinking as well as frequency of substance use in the past 90 days. Variables were assessed at baseline and at 3-, 6-, and 12-month follow-up points. Measures used included self-report of relapse and urinalysis drug and alcohol screenings. RESULTS:Compared with TAU, participants assigned to MBRP and RP reported significantly lower risk of relapse to substance use and heavy drinking and, among those who used substances, significantly fewer days of substance use and heavy drinking at the 6-month follow-up. Cognitive-behavioral RP showed an advantage over MBRP in time to first drug use. At the 12-month follow-up, MBRP participants reported significantly fewer days of substance use and significantly decreased heavy drinking compared with RP and TAU. CONCLUSIONS AND RELEVANCE:For individuals in aftercare following initial treatment for substance use disorders, RP and MBRP, compared with TAU, produced significantly reduced relapse risk to drug use and heavy drinking. Relapse prevention delayed time to first drug use at 6-month follow-up, with MBRP and RP participants who used alcohol also reporting significantly fewer heavy drinking days compared with TAU participants. At 12-month follow-up, MBRP offered added benefit over RP and TAU in reducing drug use and heavy drinking. Targeted mindfulness practices may support long-term outcomes by strengthening the ability to monitor and skillfully cope with discomfort associated with craving or negative affect, thus supporting long-term outcomes. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT01159535

Project description:Long-acting, injectable, second-generation antipsychotic medication has tremendous potential to bring clinical stability to persons with schizophrenia. However, long-acting medications are rarely used following a first episode of schizophrenia.To compare the clinical efficacy of the long-acting injectable formulation of risperidone with the oral formulation in the early course of schizophrenia.A randomized clinical trial performed at a university-based research clinic, between 2005 and 2012. Eighty-six patients with recent onset of schizophrenia were randomized to receive long-acting injectable risperidone or oral risperidone. Half of each group was simultaneously randomized to receive cognitive remediation to improve cognitive functioning or healthy-behaviors training to improve lifestyle habits and well-being. An intent-to-treat analysis was performed between October 4, 2012, and November 12, 2014.A 12-month trial comparing the long-acting injectable vs oral risperidone and cognitive remediation vs healthy-behaviors training.Psychotic relapse and control of breakthrough psychotic symptoms.Of the 86 patients randomized, 3 refused treatment in the long-acting injectable risperidone group. The psychotic exacerbation and/or relapse rate was lower for the long-acting risperidone group compared with the oral group (5% vs 33%; ?21 = 11.1; P?<?.001; relative risk reduction,?84.7%). Long-acting injectable risperidone better controlled mean levels of hallucinations and delusions throughout follow-up (? = -0.30; t68 = -2.6, P = .01). The cognitive remediation and healthy-behaviors training groups did not differ significantly regarding psychotic relapse, psychotic symptom control, or hospitalization rates, and there were no significant interactions between the 2 medications and the 2 psychosocial treatments. Discontinuations owing to inadequate clinical response were more common in the oral group than in the long-acting risperidone group (?21 = 6.1; P = .01). Adherence to oral risperidone did not appear to differ before randomization but was better for the long-acting risperidone group compared with the oral group (t80 = 5.3; P < .001). Medication adherence was associated with prevention of exacerbation and/or relapse (?21 =11.1; P = .003) and control of breakthrough psychotic symptoms (? = 0.2; t79 = 2.1; P = .04).The use of long-acting injectable risperidone after a first episode of schizophrenia has notable advantages for clinical outcomes. The key clinical advantages are apparently owing to the more consistent administration of the long-acting injectable. Such formulations should be offered earlier in the course of illness.clinicaltrials.gov Identifier: NCT00333177.

Project description:BackgroundPolyunsaturated fatty acid (PUFA) metabolism abnormalities have been long implicated in the etiology of schizophrenia. Although several randomized clinical trials have been carried out to assess the efficacy of omega-3 PUFA as add-on therapy in reducing psychopathology in populations of chronic patients with schizophrenia, only a few concern first-episode schizophrenia. The majority of these studies used a 12-week intervention based on ethyl-eicosapentaenoic acid (ethyl-EPA), however, with conflicting results. An intervention based on docosahexaenoic acid plus EPA has not been used in first-episode schizophrenia studies so far. No add-on supplementation studies have been carried out in medicated first-episode schizophrenia patients to assess the efficacy of omega-3 PUFA in preventing relapses.MethodsA randomized placebo-controlled one-center trial will be used to compare the efficacy of 26-week intervention, composed of either 1320 mg/day of EPA and 880 mg/day of DHA, or olive oil placebo with regard to symptom severity and relapse rate in first-episode schizophrenia patients. Eighty-two patients (aged 16-35) will be recruited for the study. Eligible patients will be randomly allocated to one of two intervention arms: an active arm or a placebo arm (olive oil). The primary outcome measure of the clinical evaluation is schizophrenia symptom severity measured by the Positive and Negative Syndrome Scale (PANSS). Other outcomes include depressive symptoms, patient functioning and the level of insight. Correlates of change measured during the study will include structural brain changes, oxidative stress and defense, as well as neuroplasticity indicators. Metabolic syndrome components will also be assessed throughout the study.DiscussionBy comparing 26-week administration of EPA + DHA or (placebo) olive oil as add-on therapy in reducing symptom severity and one-year relapse rate in patients with first episode schizophrenia, it is intended to provide new insights into the efficacy of omega-3 PUFA and correlates of change, and contribute to the improvement of mental health care for individuals suffering from schizophrenia.Trial registrationThis study has been registered at Clinical Trials.gov with the following number: NCT02210962 .

Project description:Chronic management of schizophrenia and schizoaffective disorders is frequently complicated by symptomatic relapse. An open-label, randomized, active-controlled, 2-year trial evaluated 710 patients with schizophrenia or related disorders who were switched from stable treatment with oral risperidone, olanzapine, or conventional neuroleptics to risperidone long-acting injectable (RLAI) or oral quetiapine. Primary effectiveness evaluation was time-to-relapse. Safety evaluations included adverse events (AEs) reported for the duration of the study, Extrapyramidal Symptom Rating Scale (ESRS), clinical laboratory tests, and vital signs. A total of 666 patients (n=329 RLAI, n=337 quetiapine) were evaluable for effectiveness measures. Baseline demographics were similar between treatment groups. Kaplan-Meier estimate of time-to-relapse was significantly longer with RLAI (p<0.0001). Relapse occurred in 16.5% of patients with RLAI and 31.3% with quetiapine. RLAI and quetiapine were both safe and well tolerated. Weight gain affected 7% of patients with RLAI and 6% with quetiapine, with mean end point increases of 1.25±6.61 and 0±6.55?kg, respectively. There were no significant between-group differences in weight gain. ESRS total scores decreased similarly after randomization to either RLAI or quetiapine. Extrapyramidal AEs occurred in 10% of patients with RLAI and 6% with quetiapine. Treatment-emergent potentially prolactin-related AEs were reported in 15 (5%) patients with RLAI and 5 (2%) patients with quetiapine; hyperprolactinemia was reported in 43 (13.1%) patients with RLAI and 5 (1.5%) patients with quetiapine. Somnolence occurred in 2% of patients with RLAI and 11% with quetiapine. To our knowledge, this is the first report of a randomized clinical trial directly comparing relapse prevention with a second-generation long-acting injectable antipsychotic and oral therapy. Time-to-relapse in stable patients with schizophrenia or schizoaffective disorder was significantly longer in patients randomized to RLAI compared with those randomized to oral quetiapine. Both antipsychotics were generally well tolerated.

Project description:Successful interventions have been developed for smoking cessation, but the success of smoking relapse prevention interventions has been limited. In particular, cognitive behavioural therapy (CBT) has been hampered by a high relapse rate. Because relapses can be due to the presence of conditions associated with tobacco consumption (such as drinking in bars with friends), virtual reality exposure therapy (VRET) can generate synthetic environments that represent risk situations for the patient in the context of relapse prevention. The primary objective of this study is to evaluate the effectiveness of CBT coupled with VRET, in comparison to CBT alone, in the prevention of smoking relapse. The secondary objectives are to assess the impact of CBT coupled with VRET on anxiety, depression, quality of life, self-esteem and addictive comorbidities (such as alcohol, cannabis, and gambling). A third objective examines the feasibility and acceptability of VR use considering elements such as presence, cybersickness and number of patients who complete the VRET program.The present study is a 14-month (2 months of therapy followed by 12 months of follow-up), prospective, comparative, randomized and open clinical trial, involving two parallel groups (CBT coupled with VRET versus CBT alone). The primary outcome is the proportion of individuals with tobacco abstinence at 6 months after the end of the therapy. Abstinence is defined by the total absence of tobacco consumption assessed during a post-test interview and with an apparatus that measures the carbon monoxide levels expired. A total of 60 individuals per group will be included.This study is the first to examine the efficacy of CBT coupled with VRET in the prevention of smoking relapse. Because VRET is simple to use and has a low cost, this interactive therapeutic method might be easily implemented in clinical practice if the study confirms its efficacy.ClinicalTrials.gov Identifier: NCT02205060 (registered 25 July 2014).

Dataset Information

A Randomized Trial of Iloperidone for Prevention of Relapse in Schizophrenia: The REPRIEVE Study.

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A Randomized Trial of Iloperidone for Prevention of Relapse in Schizophrenia: The REPRIEVE Study.

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