Long-acting Paliperidone Palmitate Research Articles

Adis summary of research: A 10-year observational study of the use, acceptability and effectiveness of long-acting paliperidone palmitate: implications for clinical decision making

Adis summary of research: A 10-year observational study of the use, acceptability and effectiveness of long-acting paliperidone palmitate: implications for clinical decision making

Retrospective Assessment of Metabolic Syndrome and Cardiovascular Disease Risk Following Monthly and Three-Month Long-Acting Paliperidone Palmitate Treatment in Schizophrenia

IntroductionPatients with schizophrenia exhibit a higher prevalence of metabolic syndrome and cardiovascular diseases compared to the general population, resulting in increased mortality rates. The extent of this risk may vary based on the specific treatment employed.ObjectivesThis study aims to compare the risk assessments of metabolic syndrome and cardiovascular diseases in schizophrenia patients who transitioned from monthly long-acting paliperidone palmitate (PP1M) treatment to three-month long-acting paliperidone palmitate (PP3M) treatment during both treatment periods.MethodsThe research was conducted at the Psychiatry Clinic and Psychotic Disorders Outpatient Clinic of Selcuk University Faculty of Medicine. Eligible participants included patients under PP3M treatment for a minimum of 6 months and undergoing continuous monitoring in the psychotic disorders outpatient clinic. Sociodemographic and clinical data, scales, laboratory values, and measurements taken both before and during the use of PP3M and PP1M were retrieved from file records, encompassing assessments, analyses, and examinations conducted in accordance with the “Psychotic Disorders - Treatment Monitoring Protocol.” Ethical approval was obtained from the Selcuk University Ethics Committee.Results Among the 31 patients transitioning from PP1M to PP3M treatment, 15 (48.4%) were female. The mean age of the patients was 44.4±14.4 years. No statistically significant differences were observed in the mean values of clinical evaluation and side effect assessment scales, body mass index (BMI), waist-to-hip ratio, systolic blood pressure, glucose levels, cholesterol levels, prolactin levels, and thyroid-stimulating hormone (TSH) measurements between the pre- and post-treatment phases (p>0.05). However, a significant difference was identified in the mean Qrisk3 values, a cardiovascular risk index, in two distinct measurements (10-year risk score: PP1M 3.7±4.2 and PP3M 4.6±4.8, p=0.003).Conclusions Our study, designed to investigate the impact of the monthly and three-month long-acting formulations of the same antipsychotic drug on patients’ clinical status, side effects, and general health parameters, found that PP3M treatment did not significantly differ from PP1M treatment in terms of Qrisk3 values. Despite the lack of statistical significance between the parameters used in Qrisk3 calculation, the observed significant difference in Qrisk3 values is attributed to variations in age. In order to promote the widespread adoption of long-acting treatments in schizophrenia management, clinicians should engage in comprehensive comparative studies assessing both efficacy and side effects.Disclosure of InterestNone Declared

A randomized, prospective, active-controlled study comparing intramuscular long-acting paliperidone palmitate versus oral antipsychotics in patients with schizophrenia at risk of violent behavior

ObjectivePaliperidone palmitate (PP) is an effective long-acting antipsychotic injection, but its impact on the behavior of schizophrenia patients with dangerous tendencies requires further investigation. This study aims to explore the effects of long-term antipsychotic treatment on this population in the community. MethodsThis 49-week, randomized controlled trial was conducted across 21 communities in Wuhan and enrolled 134 schizophrenia patients at risk for violent behavior. With a fixed block size of 10, participants were randomly assigned to receive either intramuscular PP 1-month formulation (PP1M) or oral antipsychotic medication (OAP) at a 1:1 ratio. Changes in patients' risk for violent/aggressive behavior, family burden, social, and cognitive functioning were measured using VRAPP, MOAS, PANSS, FBS, PSP, and RBANS scales from baseline to endpoint. Longitudinal data from multiple repeated measures were analyzed using linear mixed-effects models. ResultsThe study protocol was completed by 77.6% of the patients overall. Significant improvements were observed in the risk assessment scores, MOAS total score, PANSS total score, PSP total score, and FBS total score of patients in the PP1M group from baseline to the end of treatment (all P < 0.05). Importantly, compared to patients in the OAP group, the improvements in these measures were also significantly greater in the PP1M group. Commonly observed AEs, such as hyperprolactinemia (70.3% vs. 62.65%) and muscle tension (45.3% vs. 57.8%), were considered to be the PP-related AEs. Nonetheless, the differences between the two groups did not reach statistical significance, and no new safety concerns emerged. ConclusionsOur study suggests that PP long-acting injection (LAI) is a safe and effective treatment option for community-dwelling schizophrenia patients with impulsive violence and risky behaviors.

Cortical thickness, gray-white matter contrast, and intracortical myelin in first-episode schizophrenia patients treated with long-acting paliperidone palmitate versus oral antipsychotics

This longitudinal study evaluated the cortical thickness, gray-to-white matter contrast (GWC), and frontal lobe intracortical myelin (ICM) volume in first-episode schizophrenia (FES) patients treated with oral antipsychotics (OAP) versus a long-acting injectable antipsychotic, paliperidone palmitate (PP). 2D proton density and inversion recovery images, and 3D T1-weighted MPRAGE images were acquired at 3T from 68 FES patients in a randomized clinical trial with PP vs OAP. At baseline, no differences in GWC and ICM were observed between FES patients and HCs, but the thickness of the left precuneus, the right transverse temporal gyrus, and the bilateral superior temporal gyri was found to be thinner in FES patients relative to HCs. Following 9 months of antipsychotics, OAP treatment, compared to PP treatment, resulted in a more widespread cortical thickness reduction including the right lateral occipital and orbitofrontal gyri. No significant ICM and GWC changes were observed in the PP group, whereas OAP treatment led to a significant ICM volume decrease and GWC increase. A negative correlation was found between ICM changes and GWC changes within multiple frontal regions after 9 months of OAP treatment. These preliminary findings suggest that PP treatment might aid preservation of brain morphology.

Mothers and fathers with schizophrenia: Treatment and quality of life

IntroductionSchizophrenia is a chronic disease that deteriorates the functionality of patients, especially when raising a family and caring for children. We are interested in analyzing the characteristics of mothers and fathers diagnosed with schizophrenia and their degree of global activity when switching from oral treatments to injectable treatments.Objectives1 To evaluate the quality of life and functional level of mothers with schizophrenia treated with quarterly paliperidone palmitate. 2. To compare the quality of life and functional level when switching from oral treatment to long-acting injectables.MethodsParticipants were 3 mothers and 3 fathers, 33-40 years old, with a diagnosis of schizophrenia in monotherapy who changed treatment with monthly paliperidone palmitate to quarterly paliperidone palmitate LD IM (525 mg/every 12 weeks). Retrospective data collection. QLS quality of life scale.ResultsSix patients were included, caregivers of 1 child (80%), 2 children (20%) who met the inclusion criteria and completed the questionnaires. After its application and correction by means of non-parametric tests (N&lt;30). During oral treatment, scores are observed in the QLS questionnaire of: intrapsychic functions mean 34.2, interpersonal relationships mean 19, instrumental role mean 8, daily activities mean 8. After 12 months of treatment with intramuscular paliperidone palmitate (injectable every 12 weeks ) scores were obtained: intrapsychic functions mean 36, interpersonal relationships mean 23, instrumental role mean 15, daily activities mean 11. A better functioning of the patients was observed in the instrumental categories and daily activities. As well as the patients referred better adherence to treatment.ConclusionsIn our experience, injectable long-acting Paliperidone Palmitate every 12 weeks is associated with the perception of a better quality of life in parents with schizophrenia and increases administration facilities as well as planning in their daily lives.Disclosure of InterestNone Declared

Baseline risk characterization of early versus later adopters of long-acting paliperidone palmitate formulations.

Early Post‐Marketing Phase Vigilance (EPPV) is a unique system that encourages reporting of serious adverse reactions for medications newly introduced to Japan. When a once‐monthly paliperidone palmitate formulation (PP1M) was introduced in Japan in 2013, EPPV detected a signal of increased mortality, but this signal was not subsequently confirmed. To clarify whether that signal reflected increased adverse event reporting or an atypically high baseline mortality risk among early adopters of PP1M, we evaluated the baseline risk characteristics of early, mid, and later adopters of PP1M in a Japanese database and did a similar evaluation of PP1M and the three‐monthly formulation (PP3M) in two US databases. In Japan, early adopters compared with later adopters were older (mean 39.16 vs 33.70 years) but had a lower proportion of male patients (32.0% vs 44.44%), and a lower mean number of antipsychotic medications (distinct active medical substances) other than paliperidone (2.62 vs 2.85). In the United States, the baseline characteristics of early adopters of PP1M and PP3M did not suggest higher mortality risk than later adopters. These results offer no convincing evidence that the unconfirmed early signal of increased mortality with PP1M was due to increased baseline mortality risk among early adopters.

Long-acting Paliperidone Palmitate treatment in an Ekbom’s Syndrome secondary to Lewy Body Dementia: A case report

IntroductionEkbom Syndrome (ES) is a condition characterized by the fixed, delusional belief that one’s body is infested by parasites or other vermin, in absence of supporting clinical evidence. Literature suggests antipsychotic treatment for the management of behavioural and psychotic symptomatology, long-acting-injectable (LAI) antipsychotics for poor compliance.ObjectivesA case report of a 70-year-old woman with an ES diagnosis treated with LAI palmitate paliperidone was followed-up for an 8-months period, resulting in a confirmed diagnosis of secondary ES to Lewy Body Dementia (LBD).MethodsPatient was admitted to the local psychiatry ward presenting with new-onset visual and tactile hallucinations and social withdrawal. She was diagnosed with ES in a context of executive functions impairment. She was initially treated with risperidone, then switched to LAI Paliperidone due to poor compliance. Subsequently she was monitored monthly for 8 months by administering PANSS, MOCA, GAF, BPRS, PSP, complete neurocognitive assessment and neuroimaging studiesResultsAfter 8 months a progressive cognitive deterioration and worsening of motor impairment confirmed a secondary ES to a LBD. Meanwhile, a significant reduction of psychotic symptomatology (delusions and somatic hallucinations) was observed at BPRS and PANSS positive scale, even after treatment discontinuation due to the onset of extrapyramidal symptoms of the underlying condition.ConclusionsLAI Paliperidone treatment induced a complete remission of psychotic symptoms, with no relapse even after discontinuation of treatment. Moreover, close observation during follow-up allowed early diagnosis of LBD, which has been associated with a more favorable course.DisclosureNo significant relationships.

A 10-year mirror-image study of effectiveness and cost of long-acting paliperidone palmitate injectable in patients with schizophrenia or schizoaffective disorder

Acute episodes of Schizophrenia and Schizoaffective Disorder often require hospitalizations and/or psychiatry emergency room (PER) visits, with significant economic burden. Long-acting injectables (LAI), such as the once-monthly Palmitate Paliperidone LAI (1MPP) are effective in suppressing symptoms and raise treatment adherence. This study is the first aimed at evaluating long-term efficacy of initiation of 1MPP. This was a mirror-image study with a total 10 year observational length. Sample was divided into five different groups according to time span of observation: 2,4,6,8, and 10 years. Number of participants per group was 162, 129, 95, 77 and 35, respectively. Main outcomes were number and length of hospitalizations and number of PER visit. Significant reductions in these outcomes after initiation of 1MPP were found in all groups. Subgroups consisting only of patients with full adherence were evaluated, and these had better outcomes. A cost evaluation was also performed, which demonstrated decreases every year, for all main outcomes. Sensitivity analysis in the 2-year group showed results in this time-frame are independent of gender, diagnosis, previous LAI or 1MPP initiation setting. Initiation of 1MPP reduces number and length of hospitalizations up to 5 years, decreasing associated costs. This study increases evidence supporting use of 1MPP in patients with Schizophrenia or Schizoaffective disorder.

Mothers with schizophrenia: Treatment, quality of life and motherhood experience

IntroductionSchizophrenia is a chronic disease that deteriorates the functionality of patients, especially when forming a family and taking care of children. We are interested in analyzing the characteristics of mothers with schizophrenia and their degree of global activity when going from oral treatments to injectable treatments.Objectives1 To assess the quality of life and functional level of mothers with schizophrenia receiving paliperidone treatment. 2. Compare quality of life and functional level when going from oral treatment to long-term injectables.MethodsSample: Mothers, 37-45 years old, diagnosed with schizophrenia in monotherapy with oral paliperidone who started treatment with Paliperidone Palmitate LD IM (200 - 300 mg / month). Retrospective data collection. QLS quality of life scale.Results5 patients were included, caregivers of 1 child (80%), 2 children (20%) who met the inclusion criteria and completed the questionnaires. After its application and correction through non-parametric tests (N &lt;30). During oral treatment, scores were observed in the QLS questionnaire of: mean intrapsychic functions 34.2, mean interpersonal relationships 19, mean instrumental role 8, mean daily activities 8. After 12 weeks of treatment with Paliperidone Palmitate IM, scores were obtained: functions Medium intrapsychic 36, medium interpersonal relationships 23, medium instrumental role 15, medium daily activities 11. A better functioning of the patients was observed in the instrumental and daily activities categories.ConclusionsIn our experience, injectable long-acting Paliperidone Palmitate is associated with the perception of better quality of life in mothers with schizophrenia and increases the ease of administration as well as planning in their daily life.

Partial compliance with long-acting paliperidone palmitate and impact on hospitalization: a 6-year mirror-image study.

Background:Previous studies showed a linear correlation between partial compliance with an oral antipsychotic medication and hospitalisation risk among patients with schizophrenia. Long-acting injections (LAIs) may significantly improve adherence and reduce relapse in patients with psychosis. The aim of this study was to evaluate the relationship between the level of compliance with 1-monthly paliperidone palmitate (PP1M) and hospitalisation rates.Methods:This was a naturalistic, mirror-image study examining retention, compliance and hospitalisation rates 3 years pre- and 3 years post-PP1M initiation. Compliance was divided in three groups: full (no missed dose/year), good (6–11injections/year), poor (<6 injections/year).Results:A total of 173 patients suffering from a severe mental illness (70% with a diagnosis of schizophrenia and 30% with other diagnoses) were included; 77% of patients continued PP1M for 1 year, 66% for 2 years and 55% for 3 years. Of the 95 patients who remained on PP1 throughout the 3 years of follow up, 81% showed full, 13% good, and only 6% poor compliance. In the patients who were fully compliant, the mean number of hospital admissions decreased from 1.34 to 0.43, and the mean number of bed days from 82 to 19 days per patient 3 years before and 3 years after PP1M initiation (p < 0.001). It is noteworthy that the reductions in hospital stay were statistically significant for the group of patients with full compliance but not for the other two groups. In fact, patients with poor compliance demonstrated higher hospitalisation rates both before and after PPM1 initiation. These findings were similar in the subgroup of patients with schizophrenia who continued treatment for 3 years (n = 68).Conclusion:There was a direct association between partial compliance and re-hospitalisation; fully compliant patients maintained the best outcomes in terms of reduced bed use following PPM1 initiation.

Infertility after long-acting paliperidone palmitate treatment: A case report (tur)

Infertility after long-acting paliperidone palmitate treatment: A case report (tur)

Efficacy and quality of life in patients with schizophrenia and schizoaffective disorders treated with long-acting paliperidone palmitate: A naturalistic longitudinal study

IntroductionIntramuscular paliperidone palmitate (PP) is a long-acting, atypical antipsychotic for ntramuscular (IM) administration in the treatment of patients with schizophrenia.ObjectiveTo study efficacy and quality of life in patients with schizophrenia and schizoaffective disorders treated with long-acting paliperidone palmitate.MethodA non-randomized, prospective naturalistic study was performed in out-patients with schizophrenia and schizoaffective disorder unsuccessfully treated with oral antipsychotics. Efficacy of PP over time was evaluated by using BPRS 24-items (Brief Psychiatric Rating Scale) Quality of life was evaluated by the QL-Index (Quality of life Index) at T0 and at most recent visit (T1).ResultsData were available for 16 outpatients consecutively prescribed PP and naturalistically treated attending at the Psychiatric Clinic, University of Sassari. Patients were predominantly male (n = 9; 56.2%), with schizophenia (n = 10; 62.5%). Three patients dropped out (18.8%). Mean time on PP treatment was 870.0 days (sd 217.02) at a mean PP maintenance dose of 97.82 ± 37.17 mg eq. BPRS mean total score at T0 was 55 (sd 14.5) and at T1 was 44.8 (sd 11.8). Ql-Index mean total score was 5 (sd 1.6) at T0 and 7.2 (sd 2.4) at T1. Paired sample test showed a statistically significant difference in deacreasing symptoms at BPRS over time (P = 0.009) and in improving Quality of life at QL-Index (P = 0.017). The analyses showed a significant improving at the following BPRS sub-items: Depression (P = 0.021), Hostility (P = 0.022), Suspiciousness (P = 0.005), Hallucinations (P = 0.050), Unusual thought content (P = 0.029), Self-neglet (P = 0.028), Conceptual disorganization (P = 0.044), Emotional withdrawal (P = 0.028) and Distractibility (P = 0.014).Disclosure of interestThe authors have not supplied their declaration of competing interest.

The effect of long-acting paliperidone palmitate once-monthly on negative and depressive symptoms in patients with schizophrenia switched from previous unsuccessful treatment with oral aripiprazole.

The 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. Post-hoc subanalysis of 46 nonacute but symptomatic patients enrolled in a prospective, interventional, single-arm, multicenter, open-label 6-month study. At 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. Six-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.

Modeling the Time Course of the Tissue Responses to Intramuscular Long-acting Paliperidone Palmitate Nano-/Microcrystals and Polystyrene Microspheres in the Rat.

Long-acting injectable (LAI) drug suspensions consist of drug nano-/microcrystals suspended in an aqueous vehicle and enable prolonged therapeutic drug exposure up to several months. The examination of injection site reactions (ISRs) to the intramuscular (IM) injection of LAI suspensions is relevant not only from a safety perspective but also for the understanding of the pharmacokinetics. The aim of this study was to perform a multilevel temporal characterization of the local and lymphatic histopathological/immunological alterations triggered by the IM injection of an LAI paliperidone palmitate suspension and an analog polystyrene suspension in rats and identify critical time points and parameters with regard to the host response. The ISRs showed a moderate to marked chronic granulomatous inflammation, which was mediated by multiple cyto-/chemokines, including interleukin-1β, monocyte Chemoattractant Protein-1, and vascular endothelial growth factor. Lymphatic uptake and lymph node retention of nano-/microparticles were observed, but the contribution to the drug absorption was negligible. A simple image analysis procedure and empirical model were proposed for the accurate evaluation of the depot geometry, cell infiltration, and vascularization. This study was designed as a reference for the evaluation and comparison of future LAIs and to support the mechanistic modeling of the formulation-physiology interplay regulating the drug absorption from LAIs.

Effectiveness of long-acting paliperidone palmitate in borderline personality disorder.

The aim of the present study is to test the efficacy of palmitate paliperidone long-acting injection for patients with borderline personality disorder (BPD). A total of 16 patients with BPD were treated with intramuscular paliperidone palmitate (IMPP) over 12 weeks. Effectiveness measures included the CGI-BPD, HARS, MADRS, BIS-11, and STAXI-2. Functional improvement was assessed using the Global Assessment of Functioning scale. A list of adverse events was provided to clinicians and patients. Treatment with IMPP was associated with a significant average reduction of 1.6 (95% confidence interval: 1192-2008; P>0.01) in CGI-BPD scores and an average increase of psychosocial functioning as scored by the Global Assessment of Functioning scale of 13.3 (95% confidence interval: 8.35-18.31; P>0.01) was obtained. The treatment decreased impulsive-disruptive behaviors and improved general functioning. An acceptable tolerance was observed. The average weight gain was clinically irrelevant despite being statistically significant. No other relevant adverse side effects were reported, with the exception of galactorrhea, which required suspension of treatment in three patients. IMPP seems to be a well-tolerated alternative to other second-generation antipsychotics in the treatment of BPD. More controlled studies replicating these results should be proposed in the future.

Comparative effectiveness of long-acting antipsychotics: issues and challenges from a pragmatic randomised study.

Although long-acting antipsychotics are widely used in individuals with psychotic disorders, it is unclear which long-acting preparation should be considered as first-line treatment in clinical practice. In this commentary, the main strengths and weaknesses of a recently published pragmatic randomised study comparing long-acting paliperidone palmitate v. long-acting haloperidol decanoate are briefly analysed.

Long-acting paliperidone palmitate cost saving in Japan

Long-acting paliperidone palmitate cost saving in Japan

Long-acting paliperidone palmitate – interim results of an observational study of its effect on hospitalization

Paliperidone palmitate (PP) is a recently introduced long-acting atypical, or second-generation, antipsychotic. Published data on PP are currently limited to controlled trials and case reports. In this observational study, we followed up 200 consecutive patients prescribed PP in normal practice. After 1 year, 65% of patients were still receiving PP. The number of admissions to hospital in the year following PP initiation was 0.49/patient compared with 0.69/patient/year, 3 years before initiation (P=0.0001). The mean number of bed days fell from 38.78 to 23.09/patient/year over the corresponding period (P=0.0001). The median number of bed days 3 years before PP initiation was 21.50/year and in the year following PP initiation, it was 0. Outcomes were numerically but not statistically better in those continuing PP than in those who ceased PP within a year of initiation. PP was effective and well-tolerated and, given its positive effect on hospital bed days, broadly cost-effective.

Development and comparison of intramuscularly long-acting paliperidone palmitate nanosuspensions with different particle size

The main purpose of this study was to develop and compare the pharmacokinetic behavior of two paliperidone palmitate (PP) nanosuspensions with different particle size after intramuscular (i.m.) administration. PP nanosuspensions were prepared by wet media milling method and the mean particle size of nanosuspension was controlled as 1041±6nm (A) and 505±9nm (B), respectively. The morphology of nanosuspensions was observed by scanning electron microscope (SEM). Differential scanning calorimeter (DSC) and powder X-ray diffraction (PXRD) confirmed the crystallinity of PP in nanosuspensions. The physical and chemical stabilities of nanosuspensions A and B were investigated by particle analyzer and HPLC after storage for 2 months at 25°C, 4°C and mechanical shaking condition. No obvious change in particle size and chemical degradation of drug were observed. Following single-dose i.m. administration to beagle dogs, the release of paliperidone lasted for nearly 1 month. The Tmax of nanosuspensions A and B was 6 (d) and 10 (d). The AUC0–t and Cmax of nanosuspensions A was 2.0-fold and 1.8-fold higher than nanosuspensions B (p<0.05). The results demonstrated that PP nanosuspensions formulation had long-acting effect. Nanosuspension A with a larger particle size performed better than nanosuspension B. As a result, it is important to design appropriate particle size of nanosuspensions for i.m. administration in order to produce larger therapeutic effect.

EPA-1550 - Paliperidone palmitate in acute patients with schizophrenia: treatment response, safety and tolerability ? a prospective flexible-dose study in patients previously unsuccessfully treated with oral antipsychotics

Introduction This study explores tolerability, safety and treatment response of flexible doses of the atypical long-acting antipsychotic paliperidone palmitate (PP) in adult patients with an acute exacerbation of schizophrenia previously unsuccessfully treated with oral antipsychotics. Methods International prospective open-label 6-month study. Outcome parameters were change in Positive and Negative Syndrome Scale (PANSS) total score, Clinical Global Impression-Severity Scale (CGI-S), treatment-emergent adverse events (TEAEs) and weight change. Results 212 acute patients, 59.0% male, mean age 36.4 ±12.1 years, 85.4% paranoid schizophrenia were enrolled. 70.3% of patients completed the study. Most frequent reasons for early discontinuation were subject choice (9.4%), or an adverse event (9.0%). Recommended initiation regimen of PP (150 mg eq on day 1 and 100 mg eq on day 8) was administered in 92.9% of subjects. Mean baseline PANSS total score decreased from 98.5±20.1 as of day 8 of treatment to 67.4±24.0 at endpoint (mean change -31.0±28.97; 95% confidence interval [CI]-35.0;-27.1; p Conclusions These data support results from previous randomized controlled studies that flexibly dosed paliperidone palmitate is well tolerated and associated with an early and clinically relevant treatment response in acute schizophrenia patients previously unsuccessfully treated with oral antipsychotics.