Paliperidone Extended-release Research Articles

Cost-utility analysis of using paliperidone palmitate in schizophrenia in China.

Objective: Long-acting injections (LAIs) of paliperidone palmitate have been shown to improve medication adherence and relieve psychotic symptoms. However, the specific cost-utility analysis of these LAIs in schizophrenia in China remains unclear. Methods: A multi-state Markov model was constructed to simulate the economic outcomes of patients with schizophrenia in China who received paliperidone palmitate 1-month formulation (PP1M), paliperidone palmitate 3-month formulation (PP3M), and paliperidone extended-release (ER). A cost-utility analysis was conducted, mostly derived from published literature and clinical databases. All costs and utilities were discounted at a rate of 5% per annum. The primary outcome measure was the incremental cost-effectiveness ratios (ICERs). A series of sensitivity analyses were also applied. Results: After 20years, compared to ER, using PP1M resulted in an increased discounted cost from $36,252.59 to $43,207.28. This increased cost was associated with a gain in quality-adjusted life years (QALYs) from 8.60 to 9.45. As a result, the ICER for PP1M was estimated to be $8,247.46/QALY, which was lower than the willingness-to-pay (WTP) threshold of $12,756.55/QALY. When using PP3M instead of ER, the incremental cost was $768.81 and the incremental utility was 0.88 QALYs, projecting an ICER of $873.13/QALY, which was also lower than the WTP threshold of $12,756.55/QALY. The univariate sensitivity analysis showed that the costs of PP1M, PP3M, and ER had the greatest impact on ICERs. The probability sensitivity analysis (PSA) revealed that when the WTP thresholds were $12,756.55/QALY, the probability of PP1M and PP3M being cost-effective was 59.2% and 66.0%, respectively. Conclusion: From the Chinese healthcare system perspective, PP3M and PP1M are both more cost-effective compared to ER, and PP3M has notable cost-utility advantages over PP1M.

EE132 Cost-Utility Analysis of Long-Acting Injectable (1-, 3-, AND 6-MONTH INJECTION) and Oral Paliperidone in Adults with Stable Schizophrenia

To assess cost-effectiveness among long-acting injectable (LAI) paliperidone formulations administered every month (PP1M), 3 months (PP3M), or 6 months (PP6M) and oral paliperidone extended-release (ER).

Leveraging Physiologically Based Modelling to Provide Insights on the Absorption of Paliperidone Extended-Release Formulation under Fed and Fasting Conditions.

Paliperidone was approved by the US FDA in 2006 as an extended-release (ER) tablet (Invega®) for the once-daily treatment of schizophrenia. This osmotic-controlled release oral delivery system (OROS) offers advantages, such as the prevention of plasma concentration fluctuation and reduced dosing frequency. The administration of the ER after a high-fat/high-calorie meal leads to increased maximum plasma concentration and area under the curve values by 60% and 54%, respectively. Food has various effects on gastrointestinal (GI) physiology, including changed transit times, changed volumes, altered pH in different GI compartments, secretion of bile salts, and increased hepatic blood flow. This may affect solubility, the dissolution rate, absorption, and the pharmacokinetics. The aim of this study was to apply physiologically based absorption modeling (PBAM) to provide insights on paliperidone ER absorption under fed and fasting conditions. The PBAM adequately predicted absorption from the OROS formulation under both conditions. Absorption primarily occurs in the ascending colon and caecum. After a high-fat/high-calorie meal, absorption is increased through the jejunum, ileum, and colon due to either increased solubilization or the better efficiency of the OROS technology. PBAM-guided approaches can improve the understanding of branded drugs and thereby aid in guiding the development of generic formulations or formulation alternatives.

Paliperidone palmitate vs. paliperidone extended-release for the acute treatment of adults with schizophrenia: a systematic review and pairwise and network meta-analysis

Is paliperidone palmitate (PP) a useful treatment option for adults with acute symptoms of schizophrenia? We conducted a systematic review and a random-effects pairwise and network meta-analysis that compared PP (25−150 mg equivalent) with paliperidone extended-release (PAL-ER, 3−12 mg/d) regarding their efficacy and safety in adults with acute symptoms of schizophrenia. The outcomes were the total score of the Positive and Negative Syndrome Scale (PANSS-T) at week 6 (the primary outcome for efficacy) and all-cause discontinuation(the primary outcome for acceptability), discontinuation due to inefficacy, discontinuation due to adverse events, discontinuation due to the withdrawal of consent, and the incidence of individual adverse events. Five studies on PP and seven studies on PAL-ER, which involved 4970 individuals in total, were included in this study. For the primary outcomes, we only included data from the treatment arms that used 100 or 150 mg equivalent as an initial dose of PP and data from the treatment arms that used 6, 9, or 12 mg as an initial dose of PAL-ER. The pairwise meta-analyses showed that both PP and PAL-ER outperformed placebo regarding PANSS-T at week 6 and all-cause discontinuation. However, there were no statistically significant differences in these outcomes between the effect sizes of PP and that of PAL-ER. Both PP and PAL-ER increased blood prolactin levels in both females and males compared with placebo. PAL-ER significantly increased blood prolactin in both females and males compared with PP. There were no statistically significant differences in other outcomes between the effect sizes of PP and that of PAL-ER. Similar results in all outcomes were observed in the network meta-analyses. In conclusion, PP might be a useful treatment option for adults with acute symptoms of schizophrenia. A noninferiority study that directly compares PP with PAL-ER for acute schizophrenia, conducted according to the recommended regimen, is required to provide solid evidence.

EE27 Comparing Alternative Paliperidone Formulations for Relapse Prevention in Patients with Schizophrenia: A Cost-Utility Analysis

Discontinuation or poor adherence to antipsychotics in patients with schizophrenia may lead to relapses. Compared with daily administered antipsychotics (e.g., paliperidone extended-release (ER)), long-acting injectable antipsychotics (LAI) can improve medication adherence, resulting in a lower risk of relapse. Paliperidone palmitate, a new form of LAI, can be administered monthly (PP1M), three monthly (PP3M), or six-monthly (PP6M). While proven effective in improving compliance, the economic value of administering this high-cost treatment is unknown.

Paliperidone Extended Release Versus Olanzapine in Treatment-Resistant Schizophrenia: A Randomized, Double-Blind, Multicenter Study.

Paliperidone is an atypical antipsychotic as effective as other atypical antipsychotics for schizophrenia. However, few studies have explored the efficacy of paliperidone for treatment-resistant schizophrenia. This study aimed to compare the efficacy and safety of paliperidone extended release (ER) versus olanzapine in schizophrenia patients with either poor treatment response or intolerable adverse effects due to standardized antipsychotic therapy. This 12-week randomized, double-blind, multicenter study compared the treatment efficacy on psychotic symptoms, cognitive functions, and tolerance between paliperidone ER (6-15 mg/d, n = 45) and olanzapine (10-30 mg/d, n = 41) in treatment-resistant or treatment-intolerant patients with schizophrenia. The severity of psychotic symptoms was evaluated by the Positive and Negative Syndrome Scale and the Clinical Global Impression Severity of Illness Scale. The cognitive functions were assessed by the MATRICS Consensus Cognitive Battery. In addition, the metabolic impacts were evaluated by weight gain and waist circumference. Patients with either paliperidone ER or olanzapine treatment showed apparent improvement in psychotic symptoms, without significant intergroup difference. Twelve-week paliperidone ER or olanzapine treatment did not improve the cognitive functions. Both paliperidone ER and olanzapine treatment caused significant increase in weight and waist circumference, and olanzapine had a greater impact on waist circumference than paliperidone ER. In addition, both drugs were well tolerated. Paliperidone ER could be a safe alternative for treatment-resistant schizophrenia.

Assessment of the Minimum Clinically Important Difference in Symptoms and Functions of Patients With Acute Schizophrenia: A Post hoc Analysis of an Open-Label, Single-Arm Multicenter Study.

The purpose of this study was to evaluate the application of the minimum clinically important difference (MCID) concept to clinical results in Chinese patients with acutely exacerbated schizophrenia. The original study was an 8-week, open-label, single-arm, multicenter study of flexible doses of paliperidone-extended release (pali-ER) in Chinese patients with acutely exacerbated schizophrenia. This is a post hoc analysis to determine the MCID value of PANSS, PSP and evaluate the responsiveness of each outcome measurements in the acute phase of schizophrenia. The responsiveness of the four measurements (PANSS, PANSS reduction rate, PSP, CGI-S) was analyzed. Four hundred ninety nine patients completed the 8-week follow-up and were finally used for this post hoc analysis. The MCID calculated by different approaches varied from 14.02 to 31.50 for PANSS, 15.14 to 42.79% for PANSS reduction rate, and 7.62 to 13.13% for PSP. In addition, the improvement of the CGI-S owned the highest responsiveness of the four outcome measurements. The threshold value of MCID for schizophrenia patients was determined by choice of the assessment method to an extent. In addition, the CGI-S score appeared to be the most valid and responsive measure of effectiveness for the acute phase of schizophrenia when take the treatment satisfaction of patients as anchor.

Efficacy and dropout rates of antipsychotic medications for methamphetamine psychosis: A systematic review and network meta-analysis

BackgroundThis study aimed to compare the treatment effects of different antipsychotics for methamphetamine psychosis (MAP). MethodsClinical Trials, Cochrane Library, Pubmed, Scopus, and Web of Science were searched for short-term, randomized controlled trials (RCTs) from the inception to June 15, 2020. Standardized mean differences (SMDs) and odds ratios (ORs) were aggregated using random-effects pairwise comparisons and frequentist network meta-analyses (NMAs). Primary outcomes of interest were the main psychotic symptoms and dropout rates. We also rated the quality of NMA estimates. ResultsThis NMA included six RCTs of 395 patients with MAP. Six studied antipsychotics were aripiprazole, haloperidol, olanzapine, paliperidone extended-release, quetiapine, and risperidone. Risperidone is the most frequently studied antipsychotic, being investigated in four trials. Low quality of evidence was available to determine the efficacy of those antipsychotics for main psychotic symptoms. Aripiprazole was significantly inferior to olanzapine (SMD = 1.36, 95 % CI = 0.46–2.26), quetiapine (SMD = 1.13, 95 % CI = 0.28–1.98), haloperidol (SMD = 0.87, 95 % CI = 0.14–1.60), and paliperidone extended-release (SMD = 0.60, 95 % CI = 0.06–1.14). Olanzapine and quetiapine were superior to risperidone (SMD = -1.09, 95 % CI = -1.89 to -0.28 and SMD = -0.86, 95 % CI = -1.61 to -0.11, respectively). The dropout rates were not significantly different among the studied antipsychotics. ConclusionsThis analysis suggests that olanzapine or quetiapine may be a preferred antipsychotic for MAP, although the evidence for this was rated low-quality due to the high risk of bias or indirectness/intransitivity.

Randomized Controlled Trial of Paliperidone Extended Release Versus Risperidone for the Treatment of Methamphetamine-Associated Psychosis in Chinese Patients.

BackgroundThe efficacy or tolerability of paliperidone extended release (ER) in the treatment of methamphetamine (METH)-associated psychosis (MAP) is unknown. This study was designed to assess the tolerability and efficacy of paliperidone ER and risperidone for the treatment of MAP in China.MethodsThis 25-day randomized clinical trial involved 120 patients with acute MAP symptoms who were randomized to receive either paliperidone ER or risperidone from baseline to day 25 of an inpatient hospital stay. The primary outcome was changes in the severity of psychosis, which were assessed using the Positive and Negative Syndrome Scale (PANSS) total score changes from baseline to endpoint.ResultsOverall, 84% of the patients completed the entire study protocol. The PANSS total score, the Clinical Global Impressions-Severity of Illness scale (CGI-S) score, and a METH craving score assessed by a visual analog scale (VAS) showed statistically significant improvements from baseline for the patients in both groups (p < 0.01). The Simpson-Angus Scale (SAS) and the Barnes Akathisia Rating Scale (BARS) scores increased from baseline during treatment in both groups (p < 0.01); there were statistically significant differences between the treatment groups in the SAS scores (p < 0.01). Measures of hypermyotonia, salivation, and dizziness were significantly higher in the risperidone-treated patients than in the paliperidone ER-treated patients (all p < 0.05).ConclusionPaliperidone ER and risperidone had similar efficacy and were generally tolerable in the treatment of MAP; however, paliperidone ER had a more favorable adverse event profile than risperidone, particularly regarding extrapyramidal and prolactin-increasing effects.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT01822730. Full date of first registration:03/28/2013.

Cognitive functioning in adolescents with schizophrenia treated with paliperidone extended-release: 6-Month exploratory analysis from an open-label, single-arm safety study

ObjectiveTo assess cognitive functioning in adolescents (12–17 years old) with schizophrenia during open-label treatment with paliperidone extended-release (pali ER). MethodsIn this exploratory analysis, adolescents treated with pali ER (oral, flexibly dosed, 1.5–12 mg/day) underwent cognitive assessments at baseline and month 6 using a battery of cognitive tests validated in adolescents. Correlation analysis was used to explore the relationship between cognitive assessments and clinical symptoms (Positive and Negative Syndrome Scales [PANSS] and factors) and functionality (Children Global Assessment Scale [CGAS]) at baseline and at 6 months. ResultsA total of 324 of 393 patients had evaluable neurocognitive data. Changes in cognition function tests from baseline to endpoint were generally small to modest, with improvement noted for most cognitive domains (motor speed, attention/working memory, verbal learning and memory, social cognition, speed of processing, executive functioning). No improvement was noted for visual learning and memory. At baseline, there were modest negative correlations between disorganized thoughts and most cognitive domains; these correlations persisted at 6 months. Other significant negative correlations at 6 months were between speed of processing and PANSS total score, positive symptoms, negative symptoms and uncontrolled hostility (p < 0.05). At 6 months, higher CGAS scores (improved functioning) positively correlated with speed of processing and executive functioning, especially among pali ER responders. ConclusionsIn this large sample of adolescents with schizophrenia, frank cognitive deficits across multiple domains were observed. Treatment with pali ER over 6 months did not worsen neurocognitive functioning and was possibly associated with positive improvement in certain domains.

Lurasidone compared to other atypical antipsychotic monotherapies for adolescent schizophrenia: a systematic literature review and network meta-analysis

This network meta-analysis assessed the efficacy and tolerability of lurasidone versus other oral atypical antipsychotic monotherapies in adolescent schizophrenia. A systematic literature review identified 13 randomized controlled trials of antipsychotics in adolescents with schizophrenia-spectrum disorders. A Bayesian network meta-analysis compared lurasidone to aripiprazole, asenapine, clozapine, olanzapine, paliperidone extended-release (ER), quetiapine, risperidone, and ziprasidone. Outcomes included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impressions-Severity (CGI-S), weight gain, all-cause discontinuation, extrapyramidal symptoms (EPS), and akathisia. Results were reported as median differences for continuous outcomes and odds ratios (ORs) for binary outcomes, along with 95% credible intervals (95% CrI). Lurasidone was significantly more efficacious than placebo on the PANSS (− 7.95, 95% CrI − 11.76 to − 4.16) and CGI-S (− 0.44, 95% CrI − 0.67 to − 0.22) scores. Lurasidone was associated with similar weight gain to placebo and statistically significantly less weight gain versus olanzapine (− 3.62 kg, 95% CrI − 4.84 kg to − 2.41 kg), quetiapine (− 2.13 kg, 95% CrI − 3.20 kg to − 1.08 kg), risperidone (− 1.16 kg, 95% CrI − 2.14 kg to − 0.17 kg), asenapine (− 0.98 kg, 95% CrI − 1.71 kg to − 0.24 kg), and paliperidone ER (− 0.85 kg, 95% CrI − 1.57 kg to − 0.14 kg). The odds of all-cause discontinuation were significantly lower for lurasidone than aripiprazole (OR = 0.28, 95% CrI 0.10–0.76) and paliperidone ER (OR = 0.25, 95% CrI 0.08–0.81) and comparable to other antipsychotics. Rates of EPS and akathisia were similar for lurasidone and other atypical antipsychotics. In this network meta-analysis of atypical antipsychotics in adolescent schizophrenia, lurasidone was associated with similar efficacy, less weight gain, and lower risk of all-cause discontinuation compared to other oral atypical antipsychotics.

Paliperidone Extended-Release Tablets for the Treatment of Methamphetamine Use Disorder in Chinese Patients After Acute Treatment: A Randomized, Double-Blind, Placebo-Controlled Exploratory Study.

Background: To test paliperidone extended-release (ER) for efficacy in decreasing methamphetamine (METH) use and reducing psychotic symptoms in METH-dependent patients after detoxification. Rates of adverse events with paliperidone ER versus placebo were also compared. Methods: After discharge and 7 days without medication, 80 treatment-seeking METH-dependent participants were randomly assigned to paliperidone ER (3 mg once daily; n = 40) or placebo (once daily; n = 40) for 84 days under double-blind conditions. The participants attended clinics weekly to provide urine samples that were analyzed for METH metabolites, to complete research assessments, and to receive substance use and medication counseling. Results: Fifty-six percent of follow-up visits and final visits were completed. The placebo group had a significantly lower retention [51.5 days; 95% confidence interval (CI), 41.6–61.4] than the paliperidone ER group (69.4 days,; 95% CI, 61.9–76.9; p = 0.016). Paliperidone ER was a protective factor against psychotic symptom relapse [hazard ratio (HR) = 0.15, p = 0.003]. Moreover, there were statistically significant effects of paliperidone ER on psychosis severity and METH craving, assessed by mean changes in Positive and Negative Syndrome Scale (PANSS) total scores, Clinical Global Impression—Severity (CGI-S) scores, and METH craving scores over time (p = 0.006, p = 0.002, and p = 0.03 for the medication-by-time interaction effect, respectively). There were no statistically significant differences between the two groups in METH use. There were no serious adverse events related to the study drug. Conclusion: Compared with placebo, paliperidone ER administration resulted in a better retention rate and lower psychotic symptom relapse, but we did not find significantly reduced METH use among adults after acute METH detoxification treatment.

Association between symptom control and functional improvement in patients with acute schizophrenia: A post hoc analysis of an open-label, single-arm, multi-center study of paliperidone-extended release formulation

Both symptom control and functional improvement are important goals in schizophrenia treatment. A post hoc analysis of an 8-week, open-label, single-arm, multi-center study of paliperidone-extended release formulation was conducted to evaluate the correlation between personal/social functioning and symptom control in the acute phase, and to identify factors associated with psychosocial functioning, in patients with acute schizophrenia. Of 608 enrolled patients, 602 (99%) were included in the full analysis set. Correlation and regression analyses were applied to identify the association of Personal and Social Performance (PSP) total scores with Positive and Negative Syndrome Scale (PANSS) total scores and other factors. A significant negative correlation was observed between PSP and PANSS at all visits (week 1: r = −0.55; week 2: r = −0.79, p < 0.0001). Patients with PSP score improvement (≥10 point) showed a higher possibility of symptom improvement (PANSS reduction ≥30%). Duration of illness, PANSS Marder factors, and satisfaction with prior treatment, sleep quality, and daytime drowsiness influenced change in PSP total score at endpoint. These results suggest symptom outcome as an important factor to predict functional improvement in acute schizophrenia.

Paliperidone extended-release in the short- and long-term treatment of schizophrenia.

Paliperidone is a second-generation antipsychotic drug belonging to the class of benzisoxasole derivatives. Paliperidone is the major active metabolite of risperidone (9-OH-risperidone) and, as such, is comparable to the latter in terms of pharmacodynamic properties. However, due to its peculiar characteristics, paliperidone may be particularly useful in the treatment of schizophrenic patients. In this critical review of the literature the efficacy and tolerability in the short- and in the long-term have been evaluated in patients with schizophrenia. Taking into account the tolerability and efficacy data, together with the use of innovative sustained-release formulation, with a peculiar pharmacokinetic profile that allows single daily administration, paliperidone can be considered a valid option both for the short and the long-term treatment of schizophrenia.

Cost Comparison of Atypical Antipsychotics: Paliperidone ER and Risperidone.

Purpose: Paliperidone and risperidone are atypical antipsychotics that are structurally and therapeutically similar. Risperidone is metabolized by the liver via cytochrome (CYP) 2D6 to an active metabolite, 9-hydroxyrisperidone. The atypical antipsychotic paliperidone is 9-hydroxyrisperidone formulated separately as an extended-release (ER) tablet and is considerably more expensive than risperidone. The purpose of this retrospective drug utilization review is to evaluate the prescribing patterns of paliperidone ER and evaluate potential cost savings by converting paliperidone ER orders to risperidone at an inpatient psychiatric hospital's formulary. Methods: This retrospective drug utilization review includes 100 patients, older than 18 years old, who were prescribed oral paliperidone ER at an inpatient, psychiatric hospital between January 1, 2017, and June 2, 2017. The data were collected through the electronic medical records. Patients who were prescribed oral paliperidone ER and refused to take paliperidone ER were excluded from the study population. The cost of each patient's oral paliperidone ER pharmacotherapy was calculated using average wholesale prices. An equivalent total dose of risperidone therapy was calculated using a 2:3 paliperidone ER to risperidone conversion. The cost savings were then analyzed by comparing the total costs of paliperidone ER with risperidone therapy. Results: The results indicate that from January through June 2017, approximately 68% of all paliperidone ER utilization was for its approved indication of schizophrenia and schizoaffective disorder. The other 32% of utilization was either off-label or for approved indications of risperidone. The total paliperidone ER therapy cost for 100 patients was approximately $17 000, while the cost of risperidone therapy would be approximately $400 for the same patients over 6 months. Overall, this would provide an estimated cost savings of over $33 000 per year or about $169 in savings per patient. Conclusion: The study analysis demonstrates that there are opportunities for cost savings through therapeutic interchange of paliperidone ER to risperidone.

Efficacy, tolerability, and safety of oral paliperidone extended release in the treatment of schizophrenia: a 24-week, open-label, prospective switch study in different settings in Taiwan.

PurposePaliperidone extended release (ER) is an oral psychotropic treatment formulated to release paliperidone at a controlled, gradually ascending rate. We evaluated the efficacy and safety of switching to paliperidone ER in Taiwanese patients with schizophrenia who were unresponsive or intolerant to previous antipsychotic therapy.Patients and methodsThis was a 24-week, open-label, single-arm, multicenter, Phase IV trial. Based on consulting psychiatrists’ judgment, patients were deemed eligible for the switch to paliperidone ER; the switch was achieved by cross-tapering, using a recommended starting dose of 6 mg. Eligibility considerations included lack of efficacy, tolerability, and/or adherence to previous oral antipsychotic medication.ResultsOf the 297 enrolled patients, 178 (59.5%) completed the study. The main reasons for discontinuation included insufficient efficacy (8.7%), patient decision (8.4%), and adverse events (AEs; 6.4%). Improvements in the: Positive and Negative Syndrome Scale total score and Clinical Global Impression-Severity score were observed only in patients treated at medical centers and not in those treated at psychiatric hospitals. The most common AEs were insomnia, headache, constipation, and extrapyramidal syndrome. One or more serious AEs were reported in 11 (3.7%) patients; none resulted in death. No significant changes in body weight, plasma glucose, or lipid levels were observed.ConclusionSwitching to paliperidone ER was effective and well tolerated for up to 24 weeks in patients with schizophrenia who were unresponsive or intolerant to previous antipsychotic therapy. The observed differences in treatment between psychiatric hospitals and medical centers with regard to dosage and titration of paliperidone ER warrant further investigation.

Evaluation of sleep profile in schizophrenia patients treated with extended-release paliperidone: an open-label prospective study in Southeast Asia.

ObjectiveTo evaluate the effect of 6 months of treatment with paliperidone extended-release (ER) tablets on the sleep profile of patients with schizophrenia.MethodsA total of 984 patients meeting the The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for schizophrenia who switched their antipsychotic to paliperidone ER were recruited from 61 sites in five countries in Southeast Asia. We recorded patient demographics and assessed sleep quality and daytime drowsiness using visual analog scales.ResultsApproximately 70% of patients completed the 6-month study. After the use of paliperidone ER, patients reported significantly better sleep quality (76.44 vs 65.48; p<0.001) and less daytime drowsiness compared with their baseline value (23.18 vs 34.22; p<0.001). Factors predicting sleep profile improvement were completion of the study and higher baseline Positive and Negative Syndrome Scale scores.ConclusionPaliperidone ER can help schizophrenia patients to improve sleep quality and reduce daytime drowsiness; this was seen especially in the patients who completed the 6-month treatment period and had higher baseline Positive and Negative Syndrome Scale scores.

Evaluation of Potentially Prolactin-Related Adverse Events and Sexual Maturation in Adolescents with Schizophrenia Treated with Paliperidone Extended-Release (ER) for 2 Years: A Post Hoc Analysis of an Open-Label Multicenter Study.

Elevated prolactin levels (hyperprolactinemia) are a frequent adverse effect of antipsychotic medications, especially in young populations. Prolonged hyperprolactinemia may affect sexual functioning and the onset and progression of puberty. This study assessed potentially prolactin-related treatment-emergent adverse events (PPRL-TEAEs) and sexual maturation during long-term treatment of adolescents with paliperidone extended-release (ER). This post hoc analysis of a 2-year open-label multicenter study (NCT00488319) included patients of either sex aged 12-17 years at study enrollment, diagnosed with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, 4th edition [DSM-IV]) for ≥1 year, who had received one or more adequate antipsychotic treatment prior to enrollment but had not responded sufficiently. Patients were initially treated with 6mg/day paliperidone ER and further titrated between 1.5 and 12mg/day based on clinical response and tolerability. The primary objective was to determine the relationship between characteristics (including sex, age at study entry, ethnicity, geographic region, age at diagnosis, duration of illness, number of prior hospitalizations, serum prolactin, and baseline Tanner stages) and onset or risk of PPRL-TEAEs. The secondary objective was to assess sexual maturation during long-term treatment with paliperidone ER. In total, 400 patients were enrolled in the study and 184 patients completed the 2-year study; the majority were boys (61%), White (66%), and aged >14 years at study enrolment (73%) with mean (standard deviation [SD]) body mass index (BMI) of 21.96 (4.375) kg/m2 at baseline. Girls (18.5%) had a higher incidence of PPRL-TEAEs than did boys (3.3%). Most of these events were mild to moderate in severity, and none were serious; four patients discontinued the study due to PPRL-TEAEs. Mean prolactin levels in the total population of boys and girls increased early during treatment then stabilized with time. Mean ± SD maximum changes in prolactin levels from baseline were higher in girls and boys with PPRL-TEAEs than in those without (Girls: 74.7±32.3ng/ml [n=28] vs. 50.5±44.9 ng/ml [n=114]; p=0.008. Boys: 33.6±23.7 ng/ml [n=8] vs. 31.0±24.5ng/ml [n=205]; p=0.77). No clinically significant mean changes from baseline in growth-adjusted z-score for weight, height, or BMI were observed. Overall, ~90% of the patients who completed the 2-year study achieved Tanner stages 4-5 by study endpoint. Female sex, age at diagnosis (13-14 years), girls of Hispanic ethnicity, and region (EU and North America) were associated with a greater risk for PPRL-TEAEs; higher baseline Tanner stages for pubic hair (boys and girls) and breast development (stage 3 vs. 4 or 5) also seemed to be associated with a higher incidence of PPRL-TEAEs. Female sex appeared to be associated with an increased risk for PPRL-TEAEs. Other potential predictors, such as ethnicity, region, age at diagnosis, and Tanner stage 4 or 5, all seemed to be related to sex. Evidence from this study was insufficient to definitively conclude that prolactin values at baseline and change during treatment were predictive of PPRL-TEAEs, although there is a signal that this may be the case in girls. These results are exploratory in nature, and confirmatory studies are needed to confirm these observations. ClinicalTrials.gov identifier: NCT00488319.

Treatment satisfaction with paliperidone extended-release tablets: open-label study in schizophrenia patients dissatisfied with previous antipsychotic medication.

ObjectiveThe aim of this study was to evaluate the changes in treatment satisfaction after switching to paliperidone extended-release (ER) in Chinese schizophrenia patients dissatisfied with their previous antipsychotic treatment.MethodsIn this 8-week, open-label, single-arm, multicenter, prospective study, 1,693 patients dissatisfied with previous antipsychotic medication were enrolled and switched to paliperidone ER tablets (3–12 mg/d) based on clinical judgment. The primary efficacy end point was change in Medication Satisfaction Questionnaire (MSQ) score from baseline to week 8. The secondary end points included percentage of patients with MSQ score ≥4, as well as changes in Clinical Global Improvement-Severity (CGI-S) and Personal and Social Performance (PSP) scores.ResultsMSQ scores increased significantly from baseline (mean [standard deviation {SD}]: 2.48 [0.55]) to week 8 (5.47 [0.89], P<0.0001; primary end point, full analysis set). The percentage of patients with MSQ score ≥4 was 95.9% at week 8, indicating that most of the patients were satisfied with their treatment. Significant (P<0.0001) improvements from baseline to week 8 were noted in CGI-S score (2.37 [1.20]) and PSP score (25.5 [15.0]). A total of 174 (10.28%) patients experienced adverse events (AEs). The most common (>10 patients) events were extrapyramidal disorder (n=84, 4.96%), poor quality sleep (n=18, 1.06%) and akathisia (n=13, 0.77%). The majority of AEs were mild to moderate in severity. No deaths occurred.ConclusionTreatment satisfaction improved after switching to paliperidone ER from the previous antipsychotic in Chinese patients with schizophrenia.

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.