Long-acting Injectable Paliperidone Palmitate Research Articles

Prospective, randomized, multicenter clinical trial evaluating longitudinal changes in brain function and microstructure in first-episode schizophrenia patients treated with long-acting injectable paliperidone palmitate versus oral antipsychotics.

Widespread anatomical alterations and abnormal functional connectivity have shown strong association with symptom severity in first-episode schizophrenia (FES) patients. Second-generation antipsychotic treatment might slow disease progression and possibly modify the cerebral plasticity in FES patients. However, whether a long-acting injectable antipsychotic (paliperidone palmitate [PP]), available in monthly and every-3-months formulations, is more effective than oral antipsychotics (OAP) in improving cerebral organization has been unclear. Therefore, in the current longitudinal study, we evaluated the differences in functional and microstructural changes of 68 FES patients in a randomized clinical trial of PP vs OAP. When compared to OAP treatment, PP treatment was more effective in decreasing abnormally high fronto-temporal and thalamo-temporal connectivity, as well as increasing fronto-sensorimotor and thalamo-insular connectivity. Consistent with previous studies, multiple white matter pathways showed larger changes in fractional anisotropy (FA) and mean diffusivity (MD) in response to PP compared with OAP treatment. These findings suggest that PP treatment might reduce regional abnormalities and improve cerebral connectivity networks compared with OAP treatment, and identified changes that may serve as reliable imaging biomarkers associated with medication treatment efficacy.

Retrospective analysis of hospitalization rates in patients with schizophrenia 12 months before and 12 months after the switch on once-monthly long-acting injectable paliperidone palmitate

Background/Aim. There is no available published data about the use of long-acting injectable paliperidone palmitate (PP) in schizophrenia patients in the Republic of Serbia. The aim of this study was to assess hospitalization rates be-fore and after the switch to once-monthly long-acting injectable PP in schizophrenia patients, as well as their compliance with this drug. Methods. We conducted a retrospective cross-sectional study in which hospitalization rates were evaluated 12 months before and 12 months after the switch to once-monthly long-acting injectable PP in 113 schizophrenia patients. The age of the enrolled patients was between 18 and 66 years. Results. The average age of the enrolled patients was 38.36 ? 11.62 years. Among them, 77 (68.1%) were male, and 36 (31.9%) were female. Out of the total number of 113 patients treated with once-monthly injectable PP, 78 (69.03%) were on monotherapy, while 35 (30.97%) had one additional oral antipsychotic (risperidone, olanzapine, aripiprazole, or clozapine). Out of the total number of 113 patients, 68 (60.18%) were not hospitalized in the 12-month period before the switch to once-monthly long-acting injectable PP, while 45 (39.82%) were hospitalized in the same period. Given that 8 patients out of the total number of 113 were excluded from therapy due to an adverse event or their own decision in the period after the switch to PP, the analysis of the hospitalization rate after the switch to PP was performed for the remaining 105 patients, of which 9 (8.57%) were hospitalized in the period after the switch to PP, and 96 (91.43%) were not. Conclusion. Our results show high compliance in the treatment with once-monthly injectable PP and a positive impact of treatment with this drug on low hospitalization rate in a 12-month period in patients with schizophrenia. Considering the availability of this drug in the Republic of Serbia, these results encourage the use of once-monthly injectable PP as an important therapeutic option in schizophrenia patients.

Long-acting injectable paliperidone palmitate induced severe cutaneous allergic reaction in a patient with first episode delusional disorder tolerating oral paliperidone regimen: a case report

BackgroundPaliperidone is a second-generation antipsychotic agent that is effective in the treatment of schizophrenia and schizoaffective disorder as well as an adjunct to mood stabilizers and antidepressants for bipolar and depressive disorders. Paliperidone is available in both oral and injection forms. Here we report an unexpected case of cutaneous allergic reaction induced by paliperidone long-acting injection (LAI) following oral tolerance.Case presentationA 55-year-old man with first episode delusional disorder was treated with paliperidone tablets with tolerance. On day seven he received the paliperidone LAI and developed an allergic reaction in minutes including flushing of the face, widespread urticaria with mild airway constriction. The allergic symptoms were relived following the administration of antihistamine within several minutes.ConclusionThe allergic reaction that occurred post administration of the paliperidone LAI but not the oral tablets suggest it is likely due to the excipients in the formulation of the LAI rather than paliperidone itself. This case highlights the necessity of monitoring allergic reactions in psychiatric patients when converting from oral to LAI format of paliperidone.

Comparing Relapse Rates in Real-World Patients with Schizophrenia Who Were Adequately versus Not Adequately Treated with Paliperidone Palmitate Once-Monthly Injections Before Transitioning to Once-Every-3-Months Injections.

PurposeThis retrospective cohort study evaluated real-world data on relapses in adult patients with schizophrenia who transitioned to long-acting injectable paliperidone palmitate once-every-3-months (PP3M) following treatment with once-monthly paliperidone palmitate (PP1M).Patients and MethodsData derived from the IBM® MarketScan® Multi-State Medicaid Database were analyzed. Adults aged ≥18 years with ≥1 schizophrenia diagnosis claim and ≥12 months of continuous medical and prescription enrollment before and/or at index date of PP3M were eligible for inclusion. Patients were matched on propensity score to 2 PP3M cohorts: (1) adequately treated (AT), defined as patients treated with PP1M for ≥4 months, with the last 2 doses the same and a PP3M initiation dose meeting the corresponding PP1M-to-PP3M dose conversion, or (2) not adequately treated (NAT), defined as patients who received ≤2 or no PP1M doses. Relapse rates and time to relapse distributions based on the first occurrence of a qualifying event during the 2-year follow-up period were compared between PP3M cohorts using Kaplan–Meier survival curves and log rank test statistics. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. Two sensitivity analyses using different matched populations were performed to assess the robustness of the primary findings.ResultsPropensity score matching yielded a sample of 1314 patients (657 per group). Most patients were male (68.9%) and aged 25–64 years (90.1%). The relapse rate was significantly lower in the AT (18.4%) versus NAT cohort (26.8%), P = 0.0002. Risk of relapse decreased by 35% for AT versus NAT (HR: 0.65 [95% CI: 0.51–0.81]). Relapse reductions favored the AT cohort in both sensitivity analyses (HR: 0.67 [95% CI: 0.54–0.83] and HR: 0.74 [95% CI: 0.56–0.97]).ConclusionIn this analysis of Medicaid claims data, patients adequately treated with PP1M before transitioning to PP3M demonstrated significantly lower relapse rates and delayed time to relapse.

Impact of 3-Monthly Long-Acting Injectable Paliperidone Palmitate in Schizophrenia: A Retrospective, Real-World Analysis of Population-Based Health Records in Spain.

BackgroundTreatment of schizophrenia requires long-term medication to prevent relapse. Treatment nonadherence may increase the risk of relapse, leading to increased hospitalizations and emergency room (ER) visits. Long-acting injectables (LAIs) such as paliperidone palmitate have improved treatment adherence and therefore symptoms. However, real-world studies comparing 3-monthly LAI formulations with other LAIs and oral antipsychotics (OAs) are scarce.ObjectiveThe objective of this study was to investigate and evaluate the clinical effectiveness of paliperidone palmitate LAI monthly (PP1M; Xeplion®) and 3-monthly (PP3M; Trevicta®) formulations compared with the monthly LAI aripiprazole (AM; Abilify Maintena®) and OAs in Spain.MethodsThis was a retrospective, observational study including 2275 adult patients with schizophrenia in a Spanish population. Data from hospital, primary care, and pharmacy dispensation electronic medical records were obtained between January 2017 and February 2018. The main outcomes included psychiatric hospitalizations and ER visit rates, days on treatment, and treatment persistence.ResultsPatients receiving PP3M had a significantly lower mean hospitalization rate (0.00046 ± standard deviation [SD] 0.00181; p < 0.0001) than other treatment groups. Kaplan–Meier curves revealed that 92.0 and 88.4% of patients receiving PP3M remained hospitalization free by 12 and 18 months, respectively. All treatment groups had at least a twofold significantly higher risk of psychiatric hospitalizations compared with those receiving PP3M or OAs, and the hospitalization risk among the PP3M group was significantly lower (hazard ratio [HR] 0.46; 95% confidence interval [CI] 0.31–0.67). The risk of ER visits was significantly lower with both PP3M and PP1M than with OAs, and lowest with PP3M (HR 0.462 [95% CI 0.29–0.62] and HR 0.833 [95% CI 0.59–0.97], respectively). Time until treatment switch with PP3M was high, with more than 86.5% of patients remaining on treatment at 18 months.ConclusionsPP3M was more effective than OAs and monthly LAIs in improving clinical outcomes for patients with schizophrenia in a real-world setting in Spain.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40263-022-00917-1.

A health economics study of long-acting injectable once-monthly paliperidone palmitate in schizophrenia: a one-year mirror-image study in China

Schizophrenia is ranked among the top 25 leading causes of disability worldwide in 2013 which resulting in social and economic burden. By observing patients with schizophrenia one year before and after switching from oral antipsychotics (OAPs) to once-monthly paliperidone palmitate (PP1M), we can better understand the change of total costs in schizophrenic patients, including direct costs and indirect costs, after switching treatment patterns.A total of 100 schizophrenic (ICD-10) patients from Shandong Mental Health Center were collected from December 2016 to June 2019. Treatment modalities, health care resource utilization and costs were compared before and after switching directly from oral antipsychotics to PP1M.Of the 82 patients included in the main analyses, treatment with PP1M resulted in an increase in direct costs of 31.92% (P < 0.01), an increase in medicine costs of approximately 142% (P < 0.01), and a reduction in hospital costs of 68.15% (P > 0.05). There was no significant increase in total costs (P = 0.25), while 31.92% increase in direct costs (P < 0.01), and 35.62% decrease in indirect costs (P < 0.01) after conversion to PP1M. Compared with before administration of PP1M, patients with ≥ 1 inpatient stay in 1 year Pre-PP1M treatment with OAPs (n = 32) had a 20.16% decrease in direct costs (P < 0.01), a 144% increase in medicine costs (P < 0.01), and a significant 72.02% decrease in hospital costs (P < 0.01). The observed reduction in the number of hospitalizations (t = 2.56, P ≤ 0.01) and inpatient stays (t = 1.73, P < 0.05) and after transition to PP1M resulted in a reduction in hospitalization costs (P < 0.01).Switching from OAPs to PP1M decreased the household workforce burden without increasing clinical healthcare costs. Direct costs were significantly reduced in patients with ≥ 1 inpatient stay in 1 year pre-PP1M treatment with OAPs after the switch, which decreased by improving adherence to therapy and reducing the number and length of hospital stays, suggesting that those patients may benefit after switching to PP1M.

Clinical Study of Paliperidone Palmitate Long-Acting Injection Combined With Electroacupuncture in the Treatment of Methamphetamine Addicts.

Objective: To explore the clinical efficacy of paliperidone palmitate long-acting injection combined with electroacupuncture in the treatment of methamphetamine addicts. Methods: This study focused on methamphetamine addicts who were admitted to our hospital from January 2020 to December 2020 as the main research object, with a total of 89 cases. The patients were divided into a control group of 45 cases and a study group of 44 cases according to the treatment method. The control group was treated with electroacupuncture, and the study group was treated with paliperidone palmitate long-acting injection on the basis of electroacupuncture in the control group. After 6 months of continuous treatment, the treatment effect of methamphetamine withdrawal symptom score before and after treatment was used; Hamilton Anxiety Scale score and Hamilton Depression Scale were used to compare the anxiety and depression situation of the two groups; the brain wave α and θ wave situation of the two groups were compared. Result: The results showed that there was no significant difference in the scores of Ma withdrawal symptoms, Hamilton Anxiety and Hamilton Depression between the two groups before treatment (p < 0.05); after 3 and 6 months of treatment, the scores of Ma withdrawal symptoms, Hamilton Anxiety and Hamilton Depression in the study group were significantly lower than those in the control group and the difference was statistically significant (p < 0.05); 6 months after the completion of the treatment, the α wave amplitude and Fourier transformed α brain wave (FFTα) in the study group were significantly higher than those in the control group, and the difference was statistically significant (p < 0.05). Conclusion: Paliperidone palmitate long-acting injection combined with electroacupuncture is better than electroacupuncture alone in the treatment of methamphetamine addicts, and can significantly improve anxiety, depression and brain waves, thereby preventing addicts from relapse.

The effect of paliperidone palmitate long-acting injectable (PP-LAI) on "non-core" symptoms of schizophrenia: a retrospective, collaborative, multicenter study in the "real world" everyday clinical practice.

Schizophrenia is frequently complicated by the occurrence of depressive symptoms, anhedonia, obsessions and compulsions, suicidal ideation, and substance abuse, that causes exacerbations and remissions and, in several cases, sustained morbidity and disability. The present study aimed to evaluate the effect of paliperidone palmitate once-monthly long-acting injection (PP-LAI) mainly on "non-core" symptoms in persons with recent diagnosis schizophrenia, during a follow-up period of almost 12 months (T1) in the context of the "real world" everyday clinical practice. Concerning core symptoms of schizophrenia, PP-LAI was effective in reducing all symptoms at T1 as measured by Positive and Negative Syndrome Scale (PANSS), including depressive symptoms, and increased the functioning. Moreover, concerning the non-core symptoms of schizophrenia, PP-LAI treatment was effective in reducing scores of anhedonia, suicidal ideation and obsessive-compulsive symptoms at T1. However, the levels of alexithymia remained relatively stable, even if reduced. The present retrospective, multicenter, non-sponsored, collaborative study showed that early PP-LAI treatment was effective in improving almost all the core dimensions and "non-core" symptoms of schizophrenia, and this may have positive repercussions on both functioning and quality of life. PP-LAI treatment should be offered earlier as possible and was effective on "non-core" symptoms of schizophrenia at follow-up, but had a little effect on alexithymia. However, study' limitations must be considered and future researches are needed to confirm these interesting findings.

Impact of initiating long-acting injectable paliperidone palmitate on relapse and hospitalization in patients with bipolar I disorder: A mirror image retrospective study.

Literature assessing the use of long-acting injectable paliperidone palmitate in patients with bipolar I disorder is limited. The aim of this retrospective study was to determine the effectiveness of long-acting injectable paliperidone palmitate treatment on relapse and hospitalization in a real-world setting. Patients with bipolar I disorder aged 18-65 years, who were treated with paliperidone palmitate once-monthly (PP1M) for at least one year, were included. The rate of relapse, hospitalization, and length of hospital stay were collected. Safety outcomes included levels of prolactin, fasting blood sugar, total cholesterol, triglyceride, high density lipoprotein, and low density lipoprotein. The data of 36 patients who met the study criteria were evaluated. Number and length of hospitalizations, number of manic and mixed episodes significantly decreased after PP1M addition. When we compared the prolactin, fasting blood sugar, total cholesterol, triglyceride, high density lipoprotein, and low density lipoprotein levels as an indicator of the safety of treatment, there was no statistically significant change in these values before and after PP1M addition. Our findings suggested PP1M may be effective in reducing manic and mixed episodes. Limitations include a mirror image retrospective design and small sample size.

M197. SEASONAL ANTIPSYCHOTICS IN SCHIZOPHRENIA: OUTCOMES IN NATURALISTIC SETTINGS (SEASONS STUDY) OBSERVATIONAL RETROSPECTIVE MULTICENTRE CANADIAN STUDY ON 3MONTH-FORMULATION OF LONG-ACTING INJECTABLE PALIPERIDONE PALMITATE

BackgroundThe 3 month-formulation of long-acting injectable paliperidone palmitate (PP3M) is available in Canada since 2016. However, there are still limited data on its use in real life setting.MethodsThis ongoing study retrospectively reviews the use of this formulation in 6 centers across Canada (targeted n=250 patients). Data on PP3M use (dosage, duration of exposure, reasons for initiating PP3M and stopping it, if applicable) are recorded, as well as its clinical impact (hospitalizations, global severity of illness as measured by Clinical Global Impression Scales), the main outcome variable being discontinuation of PP3M.ResultsPreliminary data are available for the first 35 patients coming from 3 participating centers. 31/35 are men, on average 35 years old, Caucasian (25/35), exposed to antipsychotics for an average of 7 years (sd 2 yrs) with an average 2-year exposure to the 1-month formulation of long-acting injectable paliperidone palmitate (PP1M). 21/35 had also at least one concomitant disorder (some may be combined), such as substance use disorder, personality disorder or anxious disease, and 10/35 were under a court treatment order. Clinical Remission (as defined as a CGI S score equal or less to 3) was maintained in 27/35 subjects over an average of 14 months (sd 9 months) of PP3M. However, 8 patients stopped their treatment dues to compromise stability (2 patients), side effects (2 patients: somnolence, 1 patient: pain discomfort at site of injection) or loss to follow-up (3 patients).DiscussionIn this Canadian study, preliminary observations in real life settings suggest that PP3M may be an interesting option for patient previously stabilized on PP1M, although the number of treatment cessations might suggest that the clinical effectiveness of PP3M vs. PP1M may not be similar in all subjects.

Bir Toplum Ruh Sağılığı Merkezinde İzlenen Hastaların Klinik ve Sosyodemografik Özellikleri ile Tedavi yaklaşımlarının incelenmesi

Amaç: Bu çalışmada amaç bir Toplum Ruh Sağlığı Merkezi’nden hizmet alan hastaların klinik ve sosyodemografik özellikleri ile tedavi yaklaşımlarının incelenmesidir.Metod: Toplum ruh sağlığı merkezinde kayıtlı ve çalışmaya katılmayı kabul eden toplam 203 hastayla klinisyen yüz yüze görüşme yaparak DSM-IV tanı kriterlerine göre hastalara tanı konuldu. Kesitsel tipte olan çalışmada tüm hastalara sosyodemografik veri formu, bipolar bozukluk grubu hastalarına ise Hamilton Depresyon Derecelendirme Ölçeği (HDDÖ) ve Young Mani Derecelendirme Ölçeği (YMDÖ), psikotik bozukluk grubu hastalarına ise Pozitif ve Negatif Sendrom Ölçeği (PANSS) uygulandı.Bulgular: Çalışmamızda 52(%25,6) hastada bipolar bozukluk tanısı, 151 (%74,4) hastada psikotik bozukluk tanısı vardı. Hastaların ölçek puan ortalamaları HDDÖ 3,40±1,62, YMDÖ 2,38±0,97 ve PANSS Toplam 58,94±12,16 idi. Hastaların çoğunluğu erkek olup hanedeki ilk ve ikinci çocuklarda ruhsal hastalığın daha fazla oranda görüldüğü belirlenmiştir. 78 (%38,4) hastanın birinci derecede yakınlarında psikiyatrik hastalığın olduğu, bunun yanında 24 (%11,8) hastada adli sorun öyküsünün ve 4 (%2) hastada madde kötüye kullanımı öyküsünün olduğu görülmüştür. Tedaviye bakıldığında hastaların 29 (%14,3) kişisi risperidon uzun etkili enjeksiyon formu, 6 (%3) kişisi paliperidon palmitat uzun etkili enjeksiyon formu ve 9 (%4,4) kişisi aripiprazol uzun etkili enjeksiyon formu kullanmaktaydı.Sonuç: Bildiğimiz kadarıyla çalışmamız Türkiye’de Toplum Ruh Sağlığı Merkezi’nden hizmet alan hastaların klinik ve tedavi özelliklerini inceleyen nadir çalışmalardan biridir. Bu nedenle çalışmamızın literatür açısından önemli olduğu düşünmekteyiz.

Need for Bioequivalence Standards that Reflect the Clinical Importance of the Complex Pharmacokinetics of Paliperidone Palmitate Long-Acting Injectable Suspension.

Paliperidone palmitate is a second generation antipsychotic, approved for the treatment of schizophrenia in the form of the long-acting injectable (LAI) products INVEGA SUSTENNA® (once monthly injection) and INVEGA TRINZA® (once every 3 months injection). Paliperidone palmitate dissolves slowly after deep intramuscular injection before being hydrolyzed to paliperidone and absorbed into the systemic circulation. The pharmacokinetic (PK) profile of the INVEGA SUSTENNA® formulation is biphasic, comprised of an initial relatively fast zero-order input, which allows rapid attainment of therapeutic concentrations without oral supplementation; and a subsequent maintained second-stage, first-order input, allowing for once monthly administration. Changes to the manufacturing processes can substantially alter the release characteristics of paliperidone palmitate LAI and consequently its PK profile. As an example, larger or smaller particle sizes of paliperidone palmitate can result in a delayed or accelerated release of paliperidone into the systemic circulation, respectively. Such changes are clinically relevant, as transient excursions above therapeutic plasma concentrations can be associated with an increased risk of adverse effects, including tachycardia, hypotension, QT prolongation, and extrapyramidal symptoms. Conversely, a delay in attaining therapeutic plasma concentrations of paliperidone on initiation of treatment, or a return to low plasma concentrations before the end of a dosing interval during repeated dosing, increases the risk of relapse. Given the integral relationship of the PK profile to the product's clinical effects, it is important to have bioequivalence standards that reflect the complexity of the paliperidone palmitate LAI PK profile if one is to consider therapeutic equivalence based on simple bioequivalence testing. Although both the EMA and U.S. FDA have product-specific guidelines to determine bioequivalence, their requirements differ substantially. In Canada, no LAI product-specific bioequivalence guidance exists for multiphasic medication delivery systems, and the recently revised Comparative Bioavailability Standards: Formulations Used for Systemic Effects guidance applies only to oral and non-injectable formulations. We recommend that new Canadian standards be developed for multiphasic and biphasic intramuscular / subcutaneous (IM/SC) products, including paliperidone palmitate LAI products, because, similar to modified-release oral dosage forms, a different PK profile in modified-release IM/SC products can result in clinically meaningful differences in safety, efficacy, and tolerability. To ensure bioequivalence for both newly initiated and switch patients, this paper proposes bioequivalence standards that could be adopted in Canada that include two studies, a multiple-dose cross-over study, and a single-dose study with partial AUC metrics.

Factors Associated with the Initiation of Long-Acting Injectable Paliperidone Palmitate Versus Aripiprazole Among Medicaid Patients with Schizophrenia: An Observational Study.

Factors underlying the selection of antipsychotics for patients with schizophrenia are poorly understood. This study investigated variables associated with initiation of treatment with the long-acting injectables paliperidone palmitate (LAI-PP) and aripiprazole LAI (LAI-AP) in Medicaid patients with schizophrenia. Adults with at least one medical or pharmacy claim for LAI-PP or LAI-AP from 1 January 2013 to 31 December 2016 were selected from the IBM® MarketScan® Medicaid Database. The date of the first LAI-PP or LAI-AP claim was the index date. Patients who had at least two medical claims, on different days, for a schizophrenia diagnosis and at least 12months of continuous health plan enrollment prior to index date were included in the analysis. Multivariable logistic regression was performed to determine the factors associated with the initiation of LAI-PP versus LAI-AP. Of included patients, 5501 initiated LAI-PP and 1449 initiated LAI-AP. Patients more likely to initiate LAI-PP versus LAI-AP were older, male, or African American (all p < 0.01). Patients with obesity (odds ratio [OR] 0.84; 95% confidence interval [CI] 0.71, 0.98), post-traumatic stress disorder (OR 0.76; 95% CI 0.63, 0.92), or prior oral antipsychotic use (OR 0.66; 95% CI 0.55, 0.79) were less likely to initiate LAI-PP; whereas, patients with nonorganic psychoses (OR 1.35; 95% CI 1.18, 1.55) or prior use of other injectable antipsychotics (OR 1.26; 95% CI 1.09, 1.47) were more likely to initiate LAI-PP versus LAI-AP. Patients with at least two all-cause hospitalizations were 1.37 times more likely to initiate LAI-PP vs LAI-AP (OR 1.37; 95% CI 1.18, 1.60). Factors associated with initiating LAI-PP and LAI-AP differed. Notably, patients who initiated LAI-PP had greater prior use of medical services than LAI-AP patients. Understanding prescribing practices may help optimize treatment strategies and improve disease management. Janssen Scientific Affairs, LLC.

Adherence and economic impact of paliperidone palmitate versus oral atypical antipsychotics in a Medicare population.

Aim: To compare adherence, healthcare utilization and costs among real world, Medicare-eligible patients with schizophrenia using long-acting injectable paliperidone palmitate (PP) versus oral atypical antipsychotics. Patients &methods: Historical cohort study used Medicare Advantage claims data. Inverse probability of treatment weighting was applied to adjust for baseline differences. 12-month adherence, healthcare utilization and costs were compared. Results: Patients using PP were more adherent (proportion of days covered ≥0.8; 48.1 vs 32.6%; p <0.001), had lower odds of hospitalization (odds ratio [OR]: 0.81; 95%CI:0.68-0.96) and lower medical costs ($11,095; 95%CI: $10,374-11,867 vs $15,551; 95%CI: $14,584-16,583), but higher pharmacy costs ($14,787; 95%CI: $14,117-15,488 vs $5781; 95%CI: $5530-6043). Conclusion: Compared with patients using oral atypical antipsychotics, PP had lower hospitalizations and medical costs with greater medication adherence accompanied by higher pharmacy costs.

Long-acting injectable paliperidone palmitate for schizophrenia and alcohol use disorder

Long-acting injectable paliperidone palmitate for schizophrenia and alcohol use disorder

P.3.f.018 - The influence of the introduction of paliperidone palmitate long-acting injection on oral prescription of schizophrenic patients

A history of binge-drinking decreases protein expression of the glutamate-related scaffolding protein Homer2 within the central nucleus of the amygdala (CEA), coinciding with behavioral signs of negative affect. To assess the functional relevance of this protein change for withdrawal-induced hyper-anxiety, adult (PND 56) and adolescent (PND 28) male C57BL/6J mice were administered an intra-CEA infusion of an adeno-associated viral vector (AAV) carrying either cDNA to express Homer2 (H2-cDNA) or GFP as control. Mice underwent 14 days of binge-drinking under multi-bottle, limited-access conditions and were assayed for behavioral signs of negative affect during withdrawal using the light-dark box, marble burying, and forced swim tests (FST). Following behavioral testing, all animals experienced 5 days of drinking to evaluate the effects of prior alcohol experience and Homer2 manipulation on subsequent alcohol consumption. During protracted (4 weeks) withdrawal, adolescent alcohol-experienced GFP controls showed increased signs of negative affect across all 3 assays, compared to water-drinking GFP animals, and also showed elevated alcohol consumption during the subsequent drinking period. Homer2-cDNA infusion in adolescent-onset alcohol-drinking animals was anxiolytic and reduced subsequent alcohol consumption. Conversely, Homer2-cDNA was anxiogenic and increased drinking in water-drinking adolescents. Unfortunately, the data from adult-onset alcohol-drinking animals were confounded by low alcohol consumption and negligible behavioral signs of anxiety. Nevertheless, the present results provide novel cause-effect evidence supporting a role for CEA Homer2 in the regulation of both basal anxiety and the time-dependent intensification of negative affective states in individuals with a history of binge-drinking during adolescence.

Safety and efficacy of paliperidone palmitate 1-month formulation in Chinese patients with schizophrenia: a 25-week, open-label, multicenter, Phase IV study.

RationaleLong-acting injectable (LAI) paliperidone palmitate 1-month formulation (PP1M) has demonstrated acceptable tolerability and favorable clinical outcomes in Western and Asian patients with schizophrenia. Hence, analysis of the outcomes of long-term PP1M treatment specifically in Chinese patients is of interest.ObjectiveThe aim of this study is to evaluate the long-term safety and efficacy of PP1M treatment in Chinese patients with schizophrenia.MethodsIn this 25-week, open-label, Phase IV study, patients (18–65 years) diagnosed with schizophrenia and having a baseline Positive and Negative Syndrome Scale (PANSS) total score of 60–120 (inclusive) were enrolled. All patients received injections of PP1M 150 mg eq. (day 1) and 100 mg eq. (day 8), followed by a flexible once-monthly maintenance dosing (75, 100, or 150 mg eq.).ResultsOf the 353 patients, 234 (66.3%) completed the study treatment (mean age, 31.1 years; 52.7% men). The PANSS total score (primary end point) improved significantly over the 6-month treatment period (mean [standard deviation] change from baseline to end of treatment, −27.2 [18.30]; P<0.0001). The Clinical Global Impressions-Severity and Personal and Social Performance scores (secondary end points) also improved significantly (P<0.0001). At 6 months, PP1M had a positive impact on medication satisfaction, adherence, and increased preference for LAIs. Treatment-emergent adverse events (TEAEs) were reported by 181 (51.3%) patients (TEAEs ≥5%: extrapyramidal disorder [15.3%], akathisia [10.5%], blood prolactin increase [8.8%], insomnia [5.4%]). A total of 8 deaths were reported, including 4 completed suicides.ConclusionLong-term treatment with PP1M was efficacious, and no new safety concerns were identified in Chinese patients with schizophrenia. Overall, the results were comparable with observations from previous studies.

Effectiveness of paliperidone palmitate long-acting injectable in the initial stages of psychosis: Clinical and functional impact

IntroductionAn appropriate early intervention (EI) after the onset of a first episode of psychosis (FEP) is a key factor to prevent relapse, cognitive and functional impairment related to neurotoxicity as it is a critical period in order to get good adherence to treatment. This is the most reported factor linked to relapse. Therefore, interventions focused on getting good adherence to treatment may make the difference in terms of outcome.AimsTo compare relapse rates, symptom severity and level of functionality before and after treatment with Paliperidone Palmitate Long-Acting Injectable (PP-LAI). To analyze prior antipsychotic treatments and side effects registered before and after the introduction of (PP-LAI).Material and methodThis is a cross-sectional descriptive study. We analyzed a sample of 15 patients, recruited from PAFIP (an specialized EI unit) and treated with variable doses of PP-LAI. They all met diagnostic criteria for schizophrenia according to DSM-IV. Clinical and functional data of the two years before and after treatment intoroduction were recorded.ResultsTwenty-seven percent of the patients resumed their work activity or studies and 33% of the patients increased their social activity. Thirteen percent of the patients improved from negative symptoms. Prior to treatment introduction, more than a half of the simple, had suffered one or two relapses. After treatment introduction, 87% did not experience more relapses while 13% experienced another relapse.ConclusionsTreatment with PP-LAI is associated to a recovery of functional abilities, and a trend to clinical stability with high adherence to treatment related to few side effects.Disclosure of interestThe authors have not supplied their declaration of competing interest.

A case of pharmacologic extrapyramidal syndrome

IntroductionMore than 60% of patients receiving intensive treatment with first generation antipsychotic manifest some type of clinically significant extrapyramidal side effects. Parkinsonian syndrome is the most common and is characterized by rigidity, tremors, akinesia and bradykinesia and usually improves with discontinuation of antipsychotic drug or anticholinergic association.MethodsIt is a 60-year-old man, married with two children. Initiates contact with mental health in 2013 with a diagnosis of adjustment disorder. In February 2014 he requires hospitalisation, establishing the diagnosis of delusional disorder and starting treatment with long-acting injectable paliperidone palmitate (100 mg/month) with remission of psychotic symptoms in a few days. When we receive the patient in our clinic, he presents parkinsonian extrapyramidal symptoms (UKU subscale: 18), with significant functional limitation. We decrease the dose to 75 mg/month and an anticholinergic was added without improvement of Parkinsonian clinic, so we decided to switch to long-acting injectable aripiprazole 400 mg/month, objectifying complete remission of extrapyramidal syndrome (UKU subscale: 0).ConclusionsThe mechanism of action of aripiprazole m LAI (partial agonist of D2 receptors in the brain) without decreases in the nigrostriatal dopamine pathway, of improving extrapyramidal effects associated one other antipsychotics.Disclosure of interestThe authors have not supplied their declaration of competing interest.

The impact of paliperidone palmitate long-acting injection on hospital admissions in a mental health setting.

We screened 216 patients in a retrospective observational investigator-initiated study, of whom 45.37% patients (n=98) were retained after the inclusion criteria were applied. These patients had been prescribed paliperidone palmitate long-acting injection (PPLAI) with diagnoses of schizophrenia, schizoaffective disorder and bipolar affective disorder. We investigated whether PPLAI has an effect on the frequency and length of admissions to mental health inpatient units, the number of contacts with Crisis Resolution Home Treatment Teams (CRHTT) and frequency of home visits by the CRHTT per patient, over 6 years, split using a 'mirror image' method. In total, 85% of patients continued PPLAI for 1 year, 60% for 2 years and 47% for 3 years. In the sample of patients who continued with PPLAI for 3 years (n=48), the mean number of hospital admissions decreased from 1.03 to 0.35 per patient (P=0.001). The mean number of bed days decreased significantly from 53 to 24 bed days (P=0.0001). The median values showed similar significant differences. There were numerical differences but nonsignificant results between CRHTT's number of contacts and length of episodes across the study period. Our results indicate that PPLAI has been shown to be effective in the reduction of hospital admissions, relapse rates and length of inpatient stay.