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Improvement of Negative Symptoms in Schizophrenia with Paliperidone Palmitate 1-Month and 3-Month Long-Acting Injectables: Results from a Phase 3 Non-Inferiority Study.

ABSTRACT: Background:Negative symptoms in schizophrenia are associated with impairments in social and cognitive functioning leading to substantial long-term disability. Available antipsychotic treatments have demonstrated only modest benefit in the improvement of negative symptoms. Objective:To compare improvements in negative symptoms among patients treated with paliperidone palmitate 3-month (PP3M) or paliperidone palmitate 1-month (PP1M) long-acting injectable (LAI) formulations. Methods:Data from a randomized double-blind (DB), phase-3, non-inferiority study in patients with schizophrenia were analyzed. Following screening, patients entered a 17-week open-label (OL) phase to receive flexibly dosed PP1M followed by a 48-week DB phase where patients were randomized (1:1) to receive either PP1M or PP3M. Positive and Negative Syndrome Scale (PANSS) total scores with emphasis on 7-item negative subscale scores for PP1M vs PP3M were assessed. Results:Of 1429 patients enrolled, 1016 were randomized to receive PP3M (n=504) or PP1M (n=512). At baseline, mean (SD) PANSS negative subscale was 23.2 (4.60) and negative symptom factor score was 22.3 (4.87), indicating moderate-to-severe negative symptoms. Negative subscale and symptoms factor scores showed continuous improvements throughout OL (15.9 [4.99]) and DB (14.9 [4.81]) phases. Mean (SD) changes from DB baseline in the PANSS negative subscale score were comparable between PP1M (-1.4 [3.67]) and PP3M (-1.4 [3.63]) treatment groups. Conclusion:Treatment with PP3M or PP1M demonstrated comparable improvement in negative symptoms in patients with moderate-to-severe negative symptoms and in patients with prominent negative symptoms. Long-term treatment with PP3M demonstrated benefit, suggesting that continuous antipsychotic medication treatment for >1 year is needed to achieve greater benefit for negative symptoms. Trial Registration:ClinicalTrials.gov Identifier: NCT01515423.

SUBMITTER: Gopal S

PROVIDER: S-EPMC7064291 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Improvement of Negative Symptoms in Schizophrenia with Paliperidone Palmitate 1-Month and 3-Month Long-Acting Injectables: Results from a Phase 3 Non-Inferiority Study.

Gopal Srihari S Gogate Jagadish J Pungor Katalin K Kim Edward E Singh Arun A Mathews Maju M

Neuropsychiatric disease and treatment 20200306

<h4>Background</h4>Negative symptoms in schizophrenia are associated with impairments in social and cognitive functioning leading to substantial long-term disability. Available antipsychotic treatments have demonstrated only modest benefit in the improvement of negative symptoms.<h4>Objective</h4>To compare improvements in negative symptoms among patients treated with paliperidone palmitate 3-month (PP3M) or paliperidone palmitate 1-month (PP1M) long-acting injectable (LAI) formulations.<h4>Meth ...[more]

PMID: 32184607

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Project description:The pooled analysis of two double-blind, randomized, multicenter, phase-3 studies evaluated predictors of improvement or worsening of schizophrenia-related caregiver burden following paliperidone palmitate long-acting injectables (1-monthly [PP1M] and 3-monthly [PP3M]) treatment. Caregivers were offered to complete the involvement evaluation questionnaire (involvement evaluation questionnaire; 31-item scale). Total, 1498 caregivers (intent-to-treat open-label analysis set, n?=?1497; mean [SD] age: 51.5 [13.02] years, 27 countries) were included: 49% were parents and >50% caregivers spent >32?hours/week in caregiving. Majority of caregivers with considerable burden (n?=?1405; mean [SD] baseline involvement evaluation questionnaire scores: 28.4 [15.07]) improved significantly from baseline to end-of-study (n?=?756; mean [SD] change from open-label baseline to double-blind endpoint in long-acting injectable scores:-8.9 [14.73]); most improvements were seen in urging followed by worrying, tension, and supervision domains (mean [SD] change from open-label baseline to double-blind endpoint in involvement evaluation questionnaire scores, urging: -3.7 [6.45]; worrying:-2.6 [5.11]; tension:-2.3 [4.84]; supervision: -1.3 [3.69]). Improvements significantly correlated with relapse status, patient age, and age of diagnosis (p?<?0.001) while long-acting injectable use at baseline, number, and duration of prior psychiatric hospitalizations (<24 months) had no significant correlation. Caregiver burden was significantly improved for patients on prior oral antipsychotics post-switching to long-acting injectable, with less impact on leisure days and hours spent in caregiving (p?<?0.001). Family members of patients with schizophrenia experience considerable caregiver burden. Switching from oral antipsychotic to long-acting injectable can provide meaningful and significant improvement in caregiver burden.Drug formulationEASING THE TOLL OF CAREGIVING: Switching from oral to long-acting injectable antipsychotic medication improves overall caregiver burden. The physical, emotional and financial toll of providing care for patients with schizophrenia is often underestimated. Poor adherence to conventional oral antipsychotics is a major cause of symptomatic relapse in patients and of stress for carers. Srihari Gopal and colleagues at Janssen Pharmaceuticals have pooled data from two large studies involving 1498 caregivers across 27 countries. They found that administration of either 1- or 3-monthly long-acting injectable antipsychotics not only eased the burden of daily dosing and patient compliance, but also had a positive impact on the stress conditions of caregivers. Using the Involvement Evaluation Questionnaire to measure caregiver burden, the authors showed that the switch in drug formulation decreased the need to urge patients to self-care and the hours spent caregiving.

Project description:BackgroundThe negative symptoms of schizophrenia are generally harder to recognize, more difficult to treat than positive symptoms, and have a significant impact on patient functioning and overall outcomes. Treatment with aripiprazole may be associated with benefits on negative symptoms and functioning given its partial agonism to the dopamine D2 receptor. The aim of this subanalysis was to explore the impact of flexibly dosed, long-acting paliperidone palmitate once monthly (PP1M) on negative and depressive symptoms, disorganized thoughts, anxiety, extrapyramidal symptoms, and patient functioning in nonacute adult patients with schizophrenia previously unsuccessfully treated with oral aripiprazole monotherapy.MethodsPost-hoc subanalysis of 46 nonacute but symptomatic patients enrolled in a prospective, interventional, single-arm, multicenter, open-label 6-month study.ResultsAt endpoint, improvements of ⩾ 20% and ⩾ 50% in the Positive and Negative Syndrome Scale (PANSS) total score were observed in 52.2% and 21.7% of patients, respectively. Significant and clinically relevant improvements were observed at endpoint in mean (standard deviation [SD]) PANSS negative subscale score (-3.0 (5.0); p < 0.0001) and in the PANSS Marder factor scores for negative symptoms (-2.9 (5.4); p = 0.0006), disorganized thoughts (-2.8 (4.3); p < 0.0001) and anxiety/depression (-1.8 (3.9); p = 0.0031). Patient functioning assessed by mean (SD) Personal and Social Performance scale score (3.9 (13.2); p = 0.0409), Mini International Classification of Functioning rating for Activity and Participation Disorders in Psychological Illnesses total scores (-2.9 (7.1); p = 0.0079), and Extrapyramidal Symptom Rating Scale scores (-0.6 (3.4); p = 0.0456) improved significantly at endpoint. PP1M was well tolerated with no new safety signals.ConclusionsSix-month treatment with flexibly dosed PP1M was associated with significant and clinically relevant improvements in negative and depressive symptoms, disorganized thoughts, functioning, and extrapyramidal symptoms in nonacute but symptomatic patients with schizophrenia previously unsuccessfully treated with oral aripiprazole.

Project description:BackgroundEnvironmental impact assessments of pharmaceuticals typically consider only a part of the pharmaceutical supply chain, e.g. tablet formulation. While the environmental impact can be expressed in environmental Human Health burden due to resource use and emissions, the Human Health benefit of the pharmaceutical treatment of patients is currently not simultaneously taken into account. The study aims include a cradle-to-grave assessment of all Human Health impacts of the production, administration and disposal of two antipsychotics for the treatment of schizophrenia. This is complemented with the environmental impact of health care providers such as hospitals. The aim is to holistically quantify to what extent the environmental Human Health burden compares to the Human Health benefit associated with the treatment.MethodsWe applied an overall framework which included Life Cycle Assessment to model the environmental Human Health impacts of the pharmaceutical supply chain, administration and disposal of the drug and health care providers. To model the patient benefit, this was complemented with a Markov model with a 1-year time horizon. Three patient groups were modeled: medicine coverage of paliperidone palmitate for either one month (PP1M) or three months (PP3M) at a time, and compared to Treatment Interruption (TI) as a control group. Outcomes were quantified using Years of Life Lost (YLL), Years Lived with Disability (YLD) and Disability-Adjusted Life Years (DALY).ResultsThe main environmental impacts were visits to the psychiatrist and psychiatric hospitals. The pharmaceutical supply chain had a limited impact. For 1000 patients for 1?year, PP1M and PP3M respectively avoided 0.38 and 0.49 environmental DALYs compared to TI. PP1M and PP3M further avoided 45.60 and 57.87 YLL and 23.31 and 29.91 YLD compared to TI. The main outcome was the sum of environmental DALYs, YLL and YLD, in which PP1M and PP3M respectively avoided 69.29 and 88.26 DALYs. Alternative analysis of Quality-Adjusted Life Years confirmed the results.ConclusionsThe overall environmental burden was lower for PP1M and PP3M treatment than Treatment Interruption because patients are kept more stable, which reduces the environmental burden due to hospitals. Moreover, the Human Health burden was outweighed by the Human Health benefit.

Dataset Information

Improvement of Negative Symptoms in Schizophrenia with Paliperidone Palmitate 1-Month and 3-Month Long-Acting Injectables: Results from a Phase 3 Non-Inferiority Study.

Publications

Improvement of Negative Symptoms in Schizophrenia with Paliperidone Palmitate 1-Month and 3-Month Long-Acting Injectables: Results from a Phase 3 Non-Inferiority Study.

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