Paliperidone ER Research Articles

Extension and Further Replication of the Reliability, Criterion Validity, and Treatment Sensitivity of the PANSS10 and PANSS20 for Pediatric Trials.

Introduction: The Positive and Negative Syndrome Scale (PANSS) is a widely accepted outcome measure for pediatric schizophrenia trials; however, it has notable limitations. Psychometric investigations have shown a multifactorial structure and some items have limited utility assessing symptom severity in children. To address these issues, we developed and evaluated optimized 10- and 20-item PANSS short-forms (PANSS10 and PANSS20) using patient-level clinical trial data. This study further assesses these optimized forms using independent clinical trial data. Methods: We examined patient-level data from a randomized pediatric schizophrenia trial comparing paliperidone ER to aripiprazole. Data were accessed through the Yale Open Data Access (YODA) secure platform. Analyses included confirmatory factor analyses, graded response models, ω score reliability, internal consistency, sensitivity to change, and criterion validity versus the Clinical Global Impressions of Severity (CGI-S). Bland-Altman analyses examined score calibration versus the 30-item PANSS and inclusion cut scores. Results: Participants (N = 288) were ages 12 to 17 years (M = 15.3, SD = 1.46; 66% male). Total scores for the PANSS10 and PANSS20 showed strong correlations with the 30-item PANSS (0.90 and 0.97, respectively). Average inter-item correlations were 0.10 and 0.14 and ωTotal reliabilities were 0.74 and 0.85. Both PANSS10 and PANSS20 scores showed reliability >0.80-2.3 to 4.5 SD and -3.0 to 6.0 SD about mean symptom severity, respectively. Sensitivity to treatment was also similar (partial eta squared 0.23 and 0.22), as was correlation with CGI-S at baseline (0.45 and 0.48; not significantly different). The mean item-average discrepancy with the 30-item PANSS was 0.095 for PANSS10 and 0.033 for PANSS20. Conclusions: The optimized PANSS forms continue to show impressive reliability, validity, and calibration compared with the 30-item PANSS. Researchers should consider replacing the 30-item PANSS with the PANSS10 as a clinical outcome and screening measure due to its length and psychometric performance.

Dose Adjustment Model of Paliperidone in Patients With Acute Schizophrenia: A post hoc Analysis of an Open-Label, Single-Arm Multicenter Study.

This study aimed to investigate the factors that influenced the clinicians to adjust the paliperidone dose in the acute phase of schizophrenia. This was a post hoc study of an 8-week, open-label, single-arm multicenter trial which evaluated the efficacy, safety, and tolerability of flexible doses of paliperidone ER (3–12 mg/day) in patients with acutely exacerbated schizophrenia. Patients were divided into groups according to the dose at week 8 (3, 6, and 9–12 mg). The responder was defined as the reduction percentage in the Positive and Negative Syndrome Scale (PANSS) total score of ≥30%. According to the chi-squared automatic interaction detection algorithm, decision tree models predicting an increase in the dose of paliperidone ER were established. A decision tree, based on 4-week Marder positive factor, Clinical Global Impression (CGI), and BMI, was established to guide the dose adjustments of paliperidone ER in the acute phase of schizophrenia. The multivariable logistic regression analysis showed that lower age at onset, higher baseline PANSS positive subscale score, and lower baseline Personal and Social Performance Scale (PSP) score were significant predictors of increased dose in responders. Patients with young-onset age, severe baseline symptoms, and poor function are more likely to benefit from high dosage.

Meta-analysis of Total Effect Decomposition in the Presence of Multiple Mediators: The Example of Schizophrenia Treatment.

Causal mediation analysis addresses mechanistic questions by decomposing and quantifying effects operating through different pathways. Because most individual studies are underpowered to detect mediating effects, we outlined a parametric approach to meta-analyzing causal mediation and interaction analyses with multiple mediators, compared it with a bootstrap-based alternative, and discussed its limitations. We employed fixed- and random-effects multivariate meta-analyses to integrate evidence on treatment-mediators and mediators-outcome associations across trials. We estimated path-specific effects as functions of meta-analyzed regression coefficients; we obtained standard errors using the delta method. We evaluated the performance of this approach in simulations and applied it to assess the mediating roles of positive symptoms of schizophrenia and weight gain in the treatment effect of paliperidone ER on negative symptoms across four efficacy trials. Both simulations and the application showed that the meta-analytic approaches increased statistical power. In the application, we observed substantial mediating effects of positive symptoms (proportions mediated from fixed-effects meta-analysis: (Equation is included in full-text article.)). Weight gain may have beneficial mediating effects; however, such benefit may disappear at high doses when metabolic side effects were excessive. Meta-analyzing causal mediation analysis combines evidence from multiple sources and improves power. Targeting positive symptoms may be an effective way to reduce negative symptoms that are challenging to treat. Future work should focus on extending the existing methods to allow for more flexible modeling of mediation.

Comparison of Relapse Prevention with 3 Different Paliperidone Formulations in Patients with Schizophrenia Continuing versus Discontinuing Active Antipsychotic Treatment: A Post-Hoc Analysis of 3 Similarly Designed Randomized Studies.

BackgroundSudden discontinuation from antipsychotic treatment is a common occurrence in patients with schizophrenia. Lower rates of relapse could be expected for patients discontinuing treatment from longer-acting formulations vs their shorter-acting equivalents.ObjectiveTo compare relapse rates and time-to-relapse between the active (analogous to adherent patients) and placebo (analogous to non-adherent patients in the real-world) arms of three different formulations of paliperidone (oral paliperidone extended release [paliperidone ER], paliperidone palmitate once monthly [PP1M], and paliperidone palmitate three monthly [PP3M] long-acting injectables).MethodsData from three similarly designed, randomized relapse prevention studies in adult patients with schizophrenia were analyzed.ResultsIn total, 922 patients were included (active treatment: 473, placebo: 449). Lowest percentage of patients experienced relapse with PP3M <PP1M <paliperidone and ER, in both the active treatment (PP3M, 9% <PP1M, 18% <paliperidone ER, 22%) and placebo (PP3M, 29% <PP1M, 48% <paliperidone ER, 52%) groups. The post-discontinuation median-time-to-relapse was significantly longer with PP3M (395 days [274 days to “not-reached”])> PP1M (172 days [134–222 days])> paliperidone ER (58 days [42–114 days]) and was “not-estimable” in the active treatment group due to low relapse rates. Hazard ratios (HR) of the three paliperidone formulations relative to their respective placebos were PP3M ([HR: 3.81; 95% CI: 2.08, 6.99; P< 0.0001]> PP1M [HR: 3.60; 95% CI: 2.45, 5.28; P<0.0001]> paliperidone ER [HR: 2.83; 95% CI: 1.73, 4.63; P<0.001]).ConclusionThe lower percentage of relapse during active treatment and longer time to relapse after discontinuing active treatment with longer-duration antipsychotic formulations suggests the benefit of longer-acting over shorter-acting formulations, especially in patients susceptible to poor adherence.Clinical trial registration: paliperidone ER (NCT00086320), PP1M (NCT00111189), and PP3M (NCT01529515).

T45. A COMPARISON OF SCHIZOPHRENIA RELAPSE RATES OF 3 PALIPERIDONE FORMULATIONS, ONCE-DAILY, ONCE-MONTHLY AND ONCE EVERY-3-MONTH: POST-HOC ANALYSIS FROM 3 RANDOMIZED CONTROLLED TRIALS

BackgroundPoor adherence to antipsychotic treatment in patients with schizophrenia can result in recurrent relapses, worsening disease, functional impairment and reduction in treatment responsiveness. Long-acting antipsychotic formulations can maintain therapeutic plasma levels for longer durations, reducing dosing frequency and delaying time to relapse compared to oral formulations. Consequently, relatively lower rates of relapse can be expected in patients on long-acting injectables (LAIs) who have discontinued treatment versus those discontinuing oral medications of the same antipsychotic. However, there is no available evidence to support this association. In this post hoc analysis, the percentage of patients who relapsed and the time to relapse for three different formulations of the same molecule (oral paliperidone extended release [ER]; paliperidone palmitate once monthly [PP1M] LAI, and paliperidone palmitate three monthly [PP3M] LAI) were evaluated in adults with schizophrenia, comparing the active and placebo arms.MethodsData from three similarly designed, randomized, double-blind, placebo-controlled relapse prevention studies in adult patients with schizophrenia (DSM-IV-TR criteria) with similar inclusion/exclusion and relapse criteria were analyzed. Patients stabilized during an open-label stabilization phase with either paliperidone ER, PP1M or PP3M were then randomized to receive either placebo (analogous to non-adherent patients in the real-world) or the same active treatment used during stabilization phase (analogous to adherent patients). The primary outcome in each study was the time to relapse after entering the randomization phase, estimated using Kaplan-Meier method. In this report, the percentage of patients who relapsed as well as time to relapse in the three studies were indirectly compared.ResultsIn total 922 patients were included in this analysis, 473 continued to receive the same active treatment and 449 patients were randomized to receive placebo. The percentage of patients who relapsed was lowest with PP3M as compared with PP1M and paliperidone ER in both the active treatment group (PP3M, 9% < PP1M, 18% < paliperidone ER, 22%) and placebo group (PP3M, 29% < PP1M, 48% < paliperidone ER, 52%) patients. The post discontinuation median time to relapse (95% confidence interval) in placebo group was highest with PP3M, 395 days (274 days to not reached) > PP1M, 172 days (134 to 222 days) > paliperidone ER, 58 days (42 to 114 days) but was not estimable in the paliperidone group.DiscussionTreatment with longer acting formulations of paliperidone are associated with lower percentage of relapse and longer time to relapse in patients with schizophrenia. Lower percentage of patients with relapse observed with LAI therapy (PP1M and PP3M) could presumably be due to ensured therapeutic plasma levels. The lower percentage of relapse observed with PP3M treatment as compared with PP1M and oral paliperidone ER treatment in the placebo group could be advantageous to non-adherent patients, as this mimics the real-world scenario where patients discontinue their antipsychotics suddenly. These findings are of relevance in schizophrenia patients as fewer and delayed relapses over the course of a lifetime of schizophrenia may provide higher protection against grey matter damage and help preserve functioning.

Evaluation of sleeping profile in schizophrenia patients treated with paliperidone-extended release: Result from an open labeled perspective study in south East Asia (perfect study)

ObjectiveTo evaluate the impact of treatment with paliperidone extended release for 6 months on sleeping profile in schizophrenia patients.MethodsA total of 984 patients meeting the DSM-IV criteria for schizophrenia who switched their antipsychotics to be paliperidone ER were recruited from 61 sites in five countries in Southeast Asia. We assessed patients in terms of demographic profile, sleep quality and daytime drowsiness as visual analog scale.ResultsPatients in our studies received paliperidone ER treatment for 6 months. About 70% completed the treatment. Sleep quality and also daytime drowsiness were significantly increased in patients compared with their baseline. The predictive factors that have effect on sleep profile improvement were completion of the study and baseline PANSS score.ConclusionPatients receiving paliperidone ER were found to have improvement in sleep quality and also improvement in daytime drowsiness, especially in patients within completion group and the higher baseline PANSS score.Disclosure of interestThe author has not supplied his/her declaration of competing interest.

Genome-wide association study of paliperidone efficacy.

Clinical response to the atypical antipsychotic paliperidone is known to vary among schizophrenic patients. We carried out a genome-wide association study to identify common genetic variants predictive of paliperidone efficacy. We leveraged a collection of 1390 samples from individuals of European ancestry enrolled in 12 clinical studies investigating the efficacy of the extended-release tablet paliperidone ER (n1=490) and the once-monthly injection paliperidone palmitate (n2=550 and n3=350). We carried out a genome-wide association study using a general linear model (GLM) analysis on three separate cohorts, followed by meta-analysis and using a mixed linear model analysis on all samples. The variations in response explained by each single nucleotide polymorphism (hSNP) were estimated. No SNP passed genome-wide significance in the GLM-based analyses with suggestive signals from rs56240334 [P=7.97×10 for change in the Clinical Global Impression Scale-Severity (CGI-S); P=8.72×10 for change in the total Positive and Negative Syndrome Scale (PANSS)] in the intron of ADCK1. The mixed linear model-based association P-values for rs56240334 were consistent with the results from GLM-based analyses and the association with change in CGI-S (P=4.26×10) reached genome-wide significance (i.e. P<5×10). We also found suggestive evidence for a polygenic contribution toward paliperidone treatment response with estimates of heritability, hSNP, ranging from 0.31 to 0.43 for change in the total PANSS score, the PANSS positive Marder factor score, and CGI-S. Genetic variations in the ADCK1 gene may differentially predict paliperidone efficacy in schizophrenic patients. However, this finding should be replicated in additional samples.

PM383. Early predictors of a clinical response at 8 weeks in patients with first-episode psychosis treated with paliperidone ER

PM383. Early predictors of a clinical response at 8 weeks in patients with first-episode psychosis treated with paliperidone ER

PM380. Treatment successful rate and efficacy of Paliperidone ER in patients with acute schizophrenia

PM380. Treatment successful rate and efficacy of Paliperidone ER in patients with acute schizophrenia

Opioids consumption and delusional symptomatology

IntroductionOpioids are the most powerful drugs commercialised for acute and chronic pain relief. The main emerging problem in our midst is the abuse and addiction to synthetic opioids iatrogenically established in general population.ObjectivesWe report the case of a female patient aged 48 admitted to the Acute Psychiatric Unit after a suicide attempt. She refers she finds herself more irritable and depressed since she began a treatment with oxycodone after she was diagnosed with fibromyalgia. She has lost a lot of weight, is not able to get to sleep and has become socially isolated.MethodologyDuring the first few days, the patient is uncooperative and shows a marked self-referentiality and verbalises delusional ideation related to her immediate surroundings. Once the treatment with opioids was withdrawn and we had prescribed paliperidone ER, she seemed more cooperative and calmed. She was discharged from the Psychiatric Day Hospital showing a good evolution.ResultsParanoid personality disorder (F60); mental and behavioural disorders due to use of opioids (F11); recurrent depressive disorder, current episode moderate (F33.1); fibromyalgia (M79.7).ConclusionsThe use of synthetic opioids (tramadol, fentanyl, oxycodone) in easy-to-use formats (patches, pills, dispersible tablets, lollipops) and their dissemination in pain treatment, is leading to an increase of problems related to it, both their side effects (psychotic symptoms) and the generation of misuse and addiction. We should pay greater attention to the prescription of opioids to patients with dysfunctional personality traits.Disclosure of interestThe authors have not supplied their declaration of competing interest.

De novo cost-utility analysis of oral paliperidone in the treatment of schizoaffective disorder

ObjectivesThe aim of this analysis is to compare costs and effectiveness of paliperidone ER vs. placebo in the treatment of schizoaffective disorder (SAD) in the Czech Republic based on pooled clinical trial data. MethodsA de novo micro-simulation model was developed to assess the cost-utility analysis of paliperidone vs. placebo as there is lack of clinical data comparing paliperidone to other interventions. There are no studies primarily evaluating the efficacy of treatment of SAD with other antipsychotics. The model estimated effectiveness and costs of patients with SAD every week during 24-week time horizon. The effectiveness was defined as improvement of a patient's PANSS score where utilities were assigned to each modelled PANSS score. Based on the patient level data a linear mixed-effects model was used to estimate the regression equations of percentage decrease of PANSS score from the baseline. Utilities were computed using a regression function of patients' age, sex and PANSS score, which was adapted from a clinical study of patients with schizophrenia as there are no QoL data on SAD patients. Among relevant costs, reflecting the payer's perspective, costs of pharmacotherapy, concomitant medications and outpatient care were considered. ResultsThe average ICER of paliperidone compared to placebo reached 28,935 EUR/QALY. The probability of paliperidone being cost-effective compared to placebo was 99.5%. ConclusionsTreatment of SAD with paliperidone results in acceptable ICER and high probability of being cost-effective compared to placebo. Thus, it can be considered as a cost-effective treatment of patients with SAD in the Czech Republic.

Early treatment response predicted subsequent clinical response in patients with schizophrenia taking paliperidone extended-release

This 6-week open-labeled study investigated whether early treatment response in patients receiving paliperidone extended-release (paliperidone ER) can facilitate prediction of responses at Week 6. Patients with schizophrenia or schizoaffective disorder were administered 9mg/day of paliperidone ER during the first 2 weeks, after which the dose was adjusted clinically. They were assessed on Days 0, 4, 7, 14, 28, and 42 by the Positive and Negative Syndrome Scale (PANSS). The serum concentrations of 9-hydroxyrisperidone were examined on Days 14 and 42. Among the 41 patients enrolled, 26 were classified as responders (≧50% improvement on total PANSS scores at Week 6). In the receiver-operator curves (ROC) analyses, the changes in total PANSS scores at Week 2 appeared to show more accurate predictability compared to Day 4 and Day 7. At Week 6, no significant correlation was observed between blood 9-hydroxyrisperidone concentration and the total score or changes of PANSS scores. The results suggest that early treatment response to paliperidone ER, particularly at Week 2, can serve as a suitable outcome predictor at Week 6. Using 9mg/day paliperidone ER as an initial dose for schizophrenia treatment exhibited relatively favorable tolerability and feasibility.

Manic Symptoms during a Switch from Paliperidone ER to Paliperidone Palmitate in a Patient with Schizophrenia.

Some antipsychotic drugs have treatment efficacy for mania and bipolar disorder. However, these drugs may rarely cause manic symptoms in some schizophrenic patients. We hereby report a 22-year-old female patient with schizophrenia who experienced a manic episode during a switch from paliperidone ER to paliperidone palmitate. This case is an important reminder that an abrupt switch from oral paliperidone to paliperidone palmitate may predispose certain patients to hypomanic or manic symptoms.

Flexible-dose oral paliperidone ER in non-acute schizophrenia previously unsuccessfully treated with oral risperidone

Aims: Assessment of oral paliperidone ER therapy. Methods: A subgroup analysis of patients with schizophrenia switched from unsuccessful oral risperidone therapy in a 6-month, open-label, multicenter study investigating flexibly dosed paliperidone ER. Results: 694 patients were analyzed (59.2% male; mean age: 40.0 years). Mean change in PANSS total score from baseline to end point was -14.4 ± 20.2 in patients switching due to lack of efficacy (n = 359). Mean change in PANSS total score for patients switching for other reasons (n = 319) was: -7.6 ± 17.0 (lack of tolerability, n = 175), -19.6 ± 20.3 (lack of compliance, n = 76), and -12.0 ± 16.8 (other, n = 68). Conclusion: In patients with schizophrenia previously unsuccessfully treated with oral risperidone, paliperidone ER was well tolerated and associated with a meaningful treatment response.

P.1.i.006 Brain white matter connectivity associated with treatment response to paliperidone ER treatment in patients with schizophrenia

P.1.i.006 Brain white matter connectivity associated with treatment response to paliperidone ER treatment in patients with schizophrenia

P.3.d.004 Use of paliperidone ER in patients with schizophrenia and cannabis dependence disorder: follow up over 6 months

P.3.d.004 Use of paliperidone ER in patients with schizophrenia and cannabis dependence disorder: follow up over 6 months

Clinical effectiveness and resource utilization of paliperidone ER for schizophrenia: Pharmacoepidemiologic International Longitudinal Antipsychotic Registry (PILAR)

Objective:To document prescribing patterns in clinical practice and assess long-term outcomes related to initiation of paliperidone ER and other oral antipsychotics among patients with schizophrenia in a naturalistic setting.Research design and methods:An international, non-interventional, naturalistic study of adult patients (≥18 years) with schizophrenia. Patients were assigned to the relevant treatment group (paliperidone ER or ‘all other oral antipsychotics’) after switching to, or initiating, oral antipsychotic treatment. Retrospective 12 month data collection was followed by 12 month prospective data collection, with 3-monthly assessments. The primary endpoint was time to all-cause discontinuation of new medication. Secondary endpoints included Clinical Global Impression–Severity (CGI-S) score, Clinical Global Impression–Schizophrenia (CGI-SCH) score, Personal and Social Performance (PSP) score, health-related quality of life (HR-QoL) and quality of sleep, evaluation of healthcare resource utilization and patient’s treatment satisfaction.Results:A total of 4051 patients were included in the intent-to-treat (ITT) analysis set. All-cause study discontinuation rates were comparable between the paliperidone ER group (16.8%) and the ‘all other oral antipsychotics’ group (15.5%). There was no difference in the time to discontinuation of newly initiated antipsychotic treatments between paliperidone ER and ‘all other oral antipsychotics’ groups. Paliperidone ER was associated with greater improvements from baseline to endpoint in both the PSP scale score (+14.2 vs +13.1, p = 0.041) and the physical component of quality of life (SF-12 Physical scores; +3.9 vs +2.9, p = 0.003) compared to ‘all other oral antipsychotics’. Improvements in mean CGI-S score, CGI-SCH score, HR-QoL, quality of sleep and daytime drowsiness, as well as patients’ treatment satisfaction were comparable between treatment groups. The incidence of adverse events was comparable between groups.Conclusions:This study provides valuable data on the prescribing habits and treatment outcomes associated with use of paliperidone ER in everyday clinical practice, and supports previous findings of the favorable functional improvement and treatment satisfaction associated with paliperidone ER.Clinical trial registration:NCT00696813; R076477SCH4015 (Register of German Association of Research-based Pharmaceutical Companies [VFA] http://www.vfa.de/de/arzneimittel-forschung/datenbanken-zu-arzneimitteln/nisdb).

EPA-1548 - Flexibly dosed paliperidone palmitate in non-acute patients with schizophrenia switched from previously unsuccessful monotherapy with oral atypical antipsychotics

To explore tolerability, safety and treatment response of flexibly dosed paliperidone palmitate (PP) in adult non-acute schizophrenia patients previously unsuccessfully treated with oral antipsychotic monotherapy of risperidone (RIS), paliperidone ER (Pali ER), olanzapine (OLA), quetiapine (QUE) or aripiprazole (ARI). International, prospective 6-month open-label study. Outcomes were response (≥20% improvement in Positive and Negative Syndrome Scale (PANSS) total score at endpoint), patient functioning (Personal and Social Performance scale (PSP)), treatment-emergent adverse events (TEAEs) and Extrapyramidal Symptom Rating Scale (ESRS). Intent-to-treat population: n=191 (RIS), n=104 (Pali ER), n=87 (OLA), n=46 (ARI), n=44 (QUE). Patients presented some differences in baseline demographics, e.g. in age, years since diagnosis and BMI. Baseline mean PANSS total scores ranged from 74.7±14.9 (ARI) to 70.8±13.1 (QUE) and 70.8±15.1 (RIS). Between 67.4% (ARI) and 83.2% (RIS) of patients completed the study. At endpoint, 74% (RIS), 58% (Pali ER), 61% (OLA), 66% (QUE) and 52% (ARI) of patients had improved ≥20% in PANSS total score. Mean PSP improvement at endpoint was: 10.4±13.8 (RIS), 7.0±13.8 (Pali ER), 4.5±15.9 (OLA), 7.9±12.4 (QUE) and 3.9±13.2 (ARI); all p<0.05. TEAEs reported at least once in all subgroups were injection site pain, insomnia and psychotic disorder. Mean change in ESRS from baseline to endpoint was -1.2±3.5 (RIS), - 0.7±4.1 (Pali ER), -1.3±4.4 (OLA), -0.3±3.2 (QUE) and -0.6±3.4 (ARI; p<0.05 for all except QUE). PP was well tolerated and associated with clinically relevant treatment response in patients previously unsuccessfully treated with oral atypical antipsychotic monotherapy, regardless of the medication that was switched.

EPA-1549 - A randomized, active-controlled rater-blinded 2-year study of paliperidone palmitate versus investigators’ choice of oral antipsychotic monotherapy in patients with schizophrenia (prosipal)

Recent metaanalyses have reported conflicting results on the efficacy of long-acting compared to oral antipsychotics in the prevention of relapse in patients with schizophrenia. 2-year international randomized active controlled, open-label, rater-blinded study evaluating time to relapse, relapse rates, psychotic symptoms (PANSS) and treatment-emergent adverse events (TEAEs) in recently diagnosed patients with schizophrenia (≥1-5 years) treated with a monotherapy of paliperidone palmitate (PP) compared to investigators’ choice of oral antipsychotics (oAPs), i.e. aripiprazole, olanzapine, quetiapine, paliperidone ER, risperidone or haloperidol. 715 patients (58.4% male, mean age 32.5±10.4 years, 86.2% paranoid schizophrenia, no significant differences in baseline characteristics) entered the 2-year study period (352 PP, 363 oAPs). Time to relapse was significantly longer with PP compared to oAPs (mean±SE: 616±10.9 vs 603±13.1 days, p=0.019). Relapse rates were significantly lower with PP vs oAPs (14.8% vs 20.9%; p=0.032), reflecting a relative risk reduction of 29.2%. Reduction of psychotic symptoms in PANSS was significantly superior with PP at treatment day 8 (p=0.021) and showed a trend in favor of PP at endpoint (p=0.074). TEAEs reported in ≥5% in any group (PP vs oAPs) were weight increase (15.9% vs 17.4%), headache (11.1% vs 8.5%), insomnia (9.7% vs 8.0%), schizophrenia (8.2% vs 9.6%), nasopharyngitis (7.1% vs 5.0%), injection site pain (6.8% vs 0%), anxiety (5.7% vs 4.4%), tremor (5.1% vs 2.2%) and suicidal ideation (4.5% vs 5.5%). In this randomized active controlled 2-year study PP was significantly delaying time to relapse and reducing relapse rates compared to investigators’ choice of oral APs.

Effect of parental age on treatment response in adolescents with schizophrenia

BackgroundAdvanced paternal age (APA) is associated with increased risk for schizophrenia, but its effect on treatment response has not been longitudinally studied. MethodsAssociation of parental ages at the time of the child's birth with age of onset, initial symptom severity and treatment response (to placebo and three different weight-based doses of paliperidone ER) in adolescents with schizophrenia was assessed in a post-hoc analysis using data from a 6-week double-blind study, the primary results of which are published (NCT00518323). ResultsThe mean (SD) paternal age was 29.2 (6.2) years, range (16–50) and maternal age was 26.8 (5.7) years, range (17–42) at childbirth for the 201 adolescents (ages 12–17years) included in the analysis. While parental ages were uncorrelated with age of onset or initial symptom severity, both maternal and paternal ages showed significant effects on treatment response (p<0.03) of all paliperidone ER arms versus placebo. Paternal age was significantly correlated to improvement in positive symptoms and maternal age significantly related to negative symptoms, although only paternal age remained significantly associated with the treatment response in analyses that included both parents' ages. ConclusionsAPA was associated with greater treatment response to both paliperidone ER and placebo, but not to age of onset or initial symptom severity in adolescents with schizophrenia. The results support the contention that APA-related schizophrenia has distinct underpinnings from other cases. Further studies are required to explore the role of genetic and environmental factors, and their interactions, in treatment response in this complex disorder.