Paliperidone long-acting injection in the treatment of an adolescent with schizophrenia with fluctuating mental symptoms during menstrual period: a case report.

Background: The treatment of schizophrenia, a chronic disabling psychiatric disorder, mainly relies on antipsychotics to control the disease and improve clinical symptoms. Various medication options are available, and differences in treatment effects, even for the same medication, have been noted. Treatment efficacy is correlated with the patient's sex, age, and physical condition. When a drug fails to achieve the desired effect or the symptoms are unstable, the drug dose is often increased or a change in medication is advised according to the patient's situation. Case presentation: We report the case of a 16 years-old girl with schizophrenia and apparent psychotic symptoms. According to the genetic testing results, the symptoms were effectively controlled, and she was discharged from the hospital with the prescription of paliperidone sustained-release tablets. During the follow-up, her symptoms fluctuated during menstrual period, causing her great distress. Furthermore, her compliance gradually declined during the following 2 years of treatment, and the medication was often discontinued. We changed the drug from an oral tablet to an injection preparation while maintaining the active ingredients of the drug. The patient's symptoms were significantly controlled, and no fluctuation of symptoms occurred during the menstrual cycle. Conclusion: Long-acting antipsychotic injections can be administered to female adolescents with schizophrenia who experience fluctuating psychotic symptoms during menstruation. This technique can ensure both consistency of medication and improvement in clinical symptoms.

Efficacy and safety of domestic Paliperidone extended-release tablets in the treatment of stable schizophrenia / 中国药房

OBJECTIVE To investigate the efficacy and safety of domestic Paliperidone extended-release tablets as a substitute for original Paliperidone extended-release tablets in the treatment of stable schizophrenia. METHODS A total of 65 patients with schizophrenia， who were treated with single original Paliperidone extended-release release tablets for 2 months or more in the outpatient or inpatient department of Shandong Daizhuang Hospital from June 2021 to June 2022， were collected and randomly divided into the domestic group （33 cases） and the original group （32 cases）. The domestic group was treated with the same dose of domestic Paliperidone extended-release tablets instead for 2 months， and the original group continued to use the previous dose of the original drug for 2 months. Positive and negative syndrome scale （PANSS） and treatment emergent symptom scale （TESS） were used to evaluate the two groups at the time of enrollment and the end of 1 week， 1 month and 2 months after enrollment. The incidence of ADR was calculated at the end of 2 months after enrollment. The fasting blood glucose， blood lipid indicators （triglyceride， total cholesterol， low-density lipoprotein， high-density lipoprotein， very-low-density lipoprotein）， serum prolactin levels， and paliperidone blood concentration were determined after the intravenous blood sample was collected. The ratio of paliperidone blood concentration to dose （C/D value） was calculated， and an electrocardiogram was performed. RESULTS There were 31 and 30 patients in the domestic group and the original group who completed the trial， respectively. There were no statistical significances in PANSS score， TESS score or C/D value at the time of enrollment and the end of 1 week， 1 month and 2 months after enrollment； there were no statistical significances in the levels of fasting blood glucose， blood lipid or serum prolactin at the time of enrollment and at the end of 2 months after enrollment （P＞0.05）. PANSS scores of both groups significantly decreased at the end of 1 month and 2 months after enrollment （P＜0.01）. The incidences of ADR were 25.81% in the domestic group and 30.00% in the original group， without significant difference （P＞0.05）， and there were no significant abnormalities in the electrocardiograms of the two groups. CONCLUSIONS Domestic Paliperidone extended-release tablets can directly replace the original tablets in the treatment of stable schizophrenia， and their clinical efficacy and safety are comparable.

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.

BACKGROUND: Sudden 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. OBJECTIVE: To 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). METHODS: Data from three similarly designed, randomized relapse prevention studies in adult patients with schizophrenia were analyzed. RESULTS: In total, 922 patients were included (active treatment: 473, placebo: 449). Lowest percentage of patients experienced relapse with PP3M 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]). CONCLUSION: The 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).

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

BACKGROUND: The 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. METHODS: This 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. RESULTS: Overall, 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). CONCLUSION: Paliperidone 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 REGISTRATION: ClinicalTrials.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.

OBJECTIVE: To assess cognitive functioning in adolescents (12-17 years old) with schizophrenia during open-label treatment with paliperidone extended-release (pali ER). METHODS: In 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. RESULTS: A 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. CONCLUSIONS: In 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.

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.

Delayed-Onset Toxicity in an Adolescent Case Following Attempted Suicide with an Overdose of Paliperidone Intake.

Paliperidone is a relatively novel atypical antipsychotic drug that is currently used to treat schizophrenia in adolescents and adults. The drug was generated by combining the active metabolite of risperidone, 9-hydroxyrisperidone, with osmotic controlled-release oral administration system (OROS) technology. Due to its specific design, the drug has been identified as a different form, albeit an active metabolite of risperidone. Such distinction mainly manifests itself during pharmacokinetic processes, because paliperidone is not affected by CYP2D6 metabolism. On the other hand, this drug is regularly released for a period of 24 hours. Even though it is possible to reach relevant literature on the efficacy and safety of paliperidone use in detail, limited data regarding its toxicity exists. A review of the literature in that sense, has revealed a scarce number of case reports and a retrospective study existing. Bearing in mind the specific form and design of the drug, we have hypothesized its toxicity might cause diverse clinical presentations, in the face of overdose or poisoning. This might in turn, prompt us to switch our usual evaluation and intervention practices. With this case report, we have aimed to discuss delayed onset toxicity with paliperidone overdose in an adolescent case, due to a suicide attempt with excessive intake of the medication.

Evaluation of paliperidone on social function in patients with chronic schizophrenia.

BACKGROUND: The impairment of social function is widespread in the patients with chronic schizophrenia, which seriously affects family, life and work conditions. AIMS: The main purpose of this study was to investigate the efficacy of paliperidone in the treatment of social function in chronic schizophrenia. METHODS: A total of 81 patients who met the standard criteria for schizophrenia and long-term hospitalised inpatients were randomly divided into the treatment group and normal control group following a 1- year prospective follow-up study. The reatment group (41 cases) used paliperidone extended-release tablets for reducing dosage, as appropriate, based on the original treatment strategy; and the control group (40 cases) used the former drugs. All patients were assessed using the Positive and Negative Symptom Scales (PANSS), and the Treatment Emergent Symptom Scale (TESS) was used to assess adverse drug reactions. The Hospitalised Psychiatric Patients' Social Functions Rating Scale (SSPI) was used to assess social function of participants before and after 8 weeks, 6 months and 1 year of treatment. RESULTS: At baseline there were no significant differences between the two groups in age, duration of illness, educational background and dosage of antipsychotic drugs (converted into chlorpromazine equivalency). There was statistically significant difference in PANSS positive symptoms by interaction effect (Fgroup×time=18.24, df=3237, p<0.001) and time effect (Ftime=21.66, df=3, p<0.01) and the difference in PANSS positive symptoms by grouping effect (Fgroup=0.68, df=1, p=0.41) was not statistically significant. The difference of grouping effect of PANSS negative symptoms (Fgroup=9.93, df=1, p=0.002), time effect (Ftime=279.15, df=3, p<0.001) and interaction effect (Fgroup × time=279.15, df=3237, p<0.001) were statistically significant. There were statistically significant differences in the grouping effect (Fgr oup=6.59, df=1, p=0.012), time effect (Ftime=152.97, df=3, p<0.001) and interaction effect (Fgroup × time=148.82, df=3237, p<0.001) of PANSS general pathological symptoms, the same as the total score of the PANSS, which showed large differences in grouping effect (Fg roup=7.04, df=1, p=0.001), time effect (Ftime=210.78, df=3, p<0.001) and interaction effect (Fgroup × time=205.20, df=3237, p<0.01). We found in the total SSPI score, grouping effect (Fgroup=31.70, df=1, p<0.001), time effect (Ftime=161.84, df=3, p<0.001) and interaction effect (Fgroup × time=132.74, df=3237, p<0.001) were demonstrated to be significantly different. Even though adverse reactions occurred 7 times in the treatment group and 44 times in the control group based on the Treatment Emergent Symptom Scale (TESS), incidence rate was significantly lower than that of the control group (χ²=18.854, p<0.001). CONCLUSION: Paliperidone can safely and effectively improve negative symptoms and social function in patients with chronic schizophrenia.

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.

PURPOSE: Paliperidone 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 METHODS: This 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. RESULTS: Of 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. CONCLUSION: Switching 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.

Efficacy and safety of paliperidone extended-release tablets in the treatment of schizophrenia / 中国基层医药

Objective To study the clinical effect and safety of paliperidone extended-release tablets in the treatment of schizophrenia.Methods 80 patients with schizophrenia were selected as the research subjects .Accord-ing to randomized single blind,the patients were divided into two groups ,40 cases in each group.The control group was given risperidone treatment,the observation group used paliperidone extended-release tablets treatment.The total effective rate,positive and negative symptoms score (PANSS score),mental disability score (WHO-DAS score II) and the incidence of adverse reactions were compared between the two groups .Results The clinical total effective rate (95.00%) in the observation group was significantly higher than the control group (80.00%,χ2 =4.114,P <0.05).After treatment, the PANSS score and WHO-DAS II score in the observation group were significantly decreased compared with before treatment (t =8.002,7.761,all P <0.05),which were lower than those in the control group after treatment (t =4.114,3.702,all P <0.05).The incidence rate of adverse reaction between the two groups had no statistically significant difference (7.50% vs.10.00%,χ2 =0.157,P >0.05).Conclusion The clinical efficacy of paliperidone extended-release tablets in the treatment of schizophrenia is significant ,which can effectively relieve patients with mental disorders ,and it is safe and reliable.

Associations of fatty acids with cognition, psychopathology, and brain-derived neurotrophic factor levels in patients with first-episode schizophrenia and related disorders treated with paliperidone extended release.

This study assessed fatty acid and brain-derived neurotrophic factor levels in patients with first-episode schizophrenia and related disorders. The levels of erythrocyte fatty acids and plasma brain-derived neurotrophic factor were measured at baseline and week 8 after treatment with paliperidone extended release. Cognitive function was evaluated using the Cognitive Assessment Interview and the cognition subscale of the Neuroleptic-Induced Deficit Syndrome Scale. There were significant decreases in stearic acid and nervonic acid levels and a significant increase in eicosapentaenoic acid levels after eight weeks. At week 8, cognition was positively associated with dihomo-γ-linolenic acid, linoleic acid, and eicosapentaenoic acid levels, and negatively associated with nervonic acid levels. Psychopathology was positively correlated with polyunsaturated fatty acid levels, and negatively correlated with saturated fatty acid levels at week 8. At both baseline and week 8, brain-derived neurotrophic factor level had a negative association with polyunsaturated fatty acids and a positive association with saturated fatty acids and monounsaturated fatty acids. The present study demonstrated that fatty acids have significant associations with cognition and psychopathology at week 8, and with brain-derived neurotrophic factor levels at both baseline and week 8.

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

OBJECTIVE: The 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. METHODS: In 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. RESULTS: MSQ 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. CONCLUSION: Treatment satisfaction improved after switching to paliperidone ER from the previous antipsychotic in Chinese patients with schizophrenia.

Comparative of paliperidone extended release tablets and risperidone tablets for women's glycolipid metabolism of episode schizophrenia / 药物评价研究

Objective To compare the sustained-release tablets paliperidone and risperidone tablets starting glycolipid metabolism in female patients with schizophrenia.Methods Eighty-five cases of women treated in our hospital episode schizophrenia patients were randomly divided into observation group (42 cases) and control group (43 cases).were treated with sustained-release tablets paliperidone and risperidone tablets monotherapy two months.Measuring body mass index before and after treatment (BMI),waist circumference (waist),triglyceride (TG),high density lipoprotein (HDL),fasting plasma glucose (FPG),2 h glucose after OGTT (2 h PG),Positive and Negative Syndrome scale (PANSS) for efficacy evaluation.Results Comparison minutes before treatment PANSS total score and factors,the difference was not statistically significant.After treatment,PANSS total score and factor scores,the difference was not statistically significant.Compared with the previous treatment,both groups PANSS total score and factor scores were significantly decreased after treatment,the difference was statistically significant (P ＜ 0.05).Two groups of patients before treatment indexes,the difference was not statistically significant.After treatment in the control group TG,former TC,HDLC,LDLC,BMI,and waist circumference with treatment,the difference was statistically significant (P ＜ 0.05);the observation group BMI and waist circumference compared with before treatment,the difference was statistically significant (P ＜ 0.05).After observation group TG,TC,LDLC,BMI and waist circumference were significantly lower than the control group,HDLC significantly higher,the difference was statistically significant (P ＜ 0.05).Two FPG,2hPG,SBP and DBP,the difference was not statistically significant (P ＞ 0.05).Adverse reactions in patients in the observation group were significantly lower than the control group,the difference was statistically significant (P ＜ 0.05).Conclusion The sustained-release tablets paliperidone and risperidone female first-episode schizophrenia patients have the same effect,but paliperidone extended release tablets in female patients improve blood lipids,BMI and waist circumference is superior to risperidone.

Efficacy and Tolerability of Paliperidone Extended-release in the Treatment of First-episode Psychosis: An Eight-week, Open-label, Multicenter Trial.

OBJECTIVE: We investigated the efficacy and tolerability of paliperidone extended-release (ER) tablets in patients with first-episode psychosis (n=75). METHODS: This was an 8-week, open-label, multicenter trial. The primary outcome variable was scores on the Positive and Negative Syndrome Scale (PANSS); secondary measures included the Scale for the Assessment of Negative Symptoms (SANS), the Cognitive Assessment Interview (CAI), and the Global Assessment of Functioning (GAF). To assess safety, we measured drug-related adverse events, weight, lipid-related variables, and prolactin and administered the Simpson-Angus Rating Scale (SARS), the Abnormal Involuntary Movement Scale (AIMS), the Barnes Akathisia Scale (BAS), the Arizona Sexual Experiences Scale (ASEX), and the Udvalg for Kliniske Undersogelser side effect rating scale (UKU). RESULTS: The administration of paliperidone ER resulted in significant improvement in the PANSS, SANS, CAI, and GAF scores (p＜0.001) over time. This improvement was evident as early as 1 week. The most frequent adverse events were akathisia, somnolence, anxiety, and sedation, which were well tolerated. Modest increases in weight and lipid profiles were also noted. Prolactin levels were substantially increased at the endpoint in both male and female patients. CONCLUSION: These results indicate that paliperidone ER is effective and is characterized by good tolerability in the treatment of positive and negative symptoms and cognitive functioning in first-episode psychosis.

Lithium carbonate as a treatment for paliperidone extended-release-induced leukopenia and neutropenia in a patient with schizoaffective disorder; a case report.

BACKGROUND: Antipsychotic drug treatment can potentially lead to adverse events such as leukopenia and neutropenia. Although these events are rare, they represent serious and life-threatening hematological side effects. CASE PRESENTATION: We present a case study of a patient with schizoaffective disorder in a 50-year-old woman. We report a case of paliperidone extended-release (ER)-induced leukopenia and neutropenia in a female patient with schizoaffective disorder. Initiating lithium carbonate treatment and decreasing the dose of valproic acid improved the observed leukopenia and neutropenia. This treatment did not influence psychotic symptoms. CONCLUSION: The combination of paliperidone ER and valproic acid induces increased paliperidone ER plasma levels. Lithium carbonate was successfully used to treat paliperidone ER-induced leukopenia and neutropenia.

Drug-Drug Interaction Studies of Paliperidone and Divalproex Sodium Extended-Release Tablets in Healthy Participants and Patients with Psychiatric Disorders.

The objective of these 2 phase 1, open-label, 2-treatment, single-sequence studies was to evaluate the effect of repeated oral doses of divalproex sodium extended-release (ER) on the pharmacokinetics (PK) of a single dose of paliperidone ER in healthy participants (study 1), and the effect of multiple doses of paliperidone ER on the steady-state PK of valproic acid (VPA) in patients with psychiatric disorders (study 2), respectively. In study 1 healthy participants received, in a fixed sequential order, treatment A, paliperidone ER 12 mg (day 1); treatment B, VPA 1000 mg (2 × 500 mg divalproex sodium ER) once daily (days 5 to 18) and paliperidone ER 12 mg (day 15). In study 2 patients received treatment A, VPA (days 1-7); treatment B, VPA + paliperidone ER 12 mg (days 8-12). Divalproex sodium ER doses (study 2) were individualized such that systemic therapeutic VPA exposure from prior treatment was maintained on entry into the study. PK assessments were performed at prespecified time points (paliperidone days 1 and 15 [study 1]; VPA days 7 and 12 [study 2]). The oral bioavailability of paliperidone was increased by an estimated 51% (Cmax ) and 51%-52% (AUCs) when coadministered with divalproex sodium ER. No effect on the steady-state plasma concentration of VPA was observed following repeated coadministration with paliperidone ER: the 90%CI around the VPA exposure ratios for the 2 treatments was within the 80%-125% bioequivalence criteria for Cmax,ss and AUCτ . Both VPA and paliperidone ER were well tolerated, and no new safety concerns were identified.

Therapeutic Effect of Paliperidone Extended-release Tablets in Schizophrenia Patients / 中国药师

Objective:To investigate the curative effect and prognosis of schizophrenia patients treated with paliperidone extended -release tablets.Methods:Totally 72 cases of patients with schizophrenia were divided into the observation group (n=35) and the control group ( n=37 ) according to the order of admission .The obsevation group was treated with paliperidone extended-release tab-lets, while the controll group was treated with risperidone tablets , and both groups were treated for 8 weeks.The positive and negative syndrome scale(PANSS) was used to assess the effect of the two groups , the social function defect scale (SDSS) and prognosis of the two groups were compared.Results: After the 2-week treatment, the PANSS score, positive symptom score, negative symptom score and general symptom score were all decreased in the two groups when compared with those before the treatment (P<0.05),and the scores in the observation group were lower than those in the controll group (P<0.05).After the treatment, the SDSS was significantly reduced in the two groups when compared with that before the treatment (P<0.05), and the reduction in the observation group was more notable than that in the control group (P<0.05).The total effective rate of the observation group was 94.3%, which was higher than that (67.6%) of the control group (P<0.05).The incidence of adverse reactions, such as anxiety and akathisia, and the total adverse drug reactions in the observation group were both lower than those in the control group (P<0.05).Conclusion:Paliperidone extended-release tablets can effectively relieve suffering from schizophrenia with quick effect , few adverse reactions , high safety and good effect , which is worthy of promotion in clinical use .

Efficacy and Tolerability of Paliperidone Extended-release in the Treatment of First-episode Psychosis: An Eight-week, Open-label, Multicenter Trial

OBJECTIVE: We investigated the efficacy and tolerability of paliperidone extended-release (ER) tablets in patients with first-episode psychosis (n=75). METHODS: This was an 8-week, open-label, multicenter trial. The primary outcome variable was scores on the Positive and Negative Syndrome Scale (PANSS); secondary measures included the Scale for the Assessment of Negative Symptoms (SANS), the Cognitive Assessment Interview (CAI), and the Global Assessment of Functioning (GAF). To assess safety, we measured drug-related adverse events, weight, lipid-related variables, and prolactin and administered the Simpson–Angus Rating Scale (SARS), the Abnormal Involuntary Movement Scale (AIMS), the Barnes Akathisia Scale (BAS), the Arizona Sexual Experiences Scale (ASEX), and the Udvalg for Kliniske Undersogelser side effect rating scale (UKU). RESULTS: The administration of paliperidone ER resulted in significant improvement in the PANSS, SANS, CAI, and GAF scores (p<0.001) over time. This improvement was evident as early as 1 week. The most frequent adverse events were akathisia, somnolence, anxiety, and sedation, which were well tolerated. Modest increases in weight and lipid profiles were also noted. Prolactin levels were substantially increased at the endpoint in both male and female patients. CONCLUSION: These results indicate that paliperidone ER is effective and is characterized by good tolerability in the treatment of positive and negative symptoms and cognitive functioning in first-episode psychosis.

Paliperidone extended-release tablets in Chinese patients with schizophrenia: meta-analysis of randomized controlled trials.

BACKGROUND: Previous meta-analyses have compared paliperidone extended-release (ER) tablets with other antipsychotics, but none have involved Chinese patients or studies from People's Republic of China. Further, the results of these meta-analyses may not be applicable to Chinese patients. In the present study, we evaluated the efficacy, safety, and acceptability of paliperidone ER compared with other second-generation antipsychotics (SGAs) for Chinese patients with schizophrenia. METHODS: Randomized controlled studies of paliperidone ER and other SGAs as oral monotherapy in the acute phase treatment of schizophrenia were retrieved from Medline, Embase, and the Cochrane Library (CENTRAL), as well as from Chinese databases including the China National Knowledge Infrastructure, Wanfang, and VIP Information/Chinese Scientific Journals Database. We pooled data on response rates, chance of withdrawal due to adverse events, probability of adverse events, and odds of withdrawal for any reason. RESULTS: Fifty randomized controlled trials were identified. The response rate for paliperidone ER was significantly higher than that of other pooled SGAs (risk ratio [RR] 0.83, 95% confidence interval [CI] 0.72-0.96) and ziprasidone (RR 0.57, 95% CI 0.39-0.82). Paliperidone ER significantly reduced the chance of withdrawal due to adverse events and the chance of any adverse events compared with other pooled SGAs (RR 0.32, 95% CI 0.17-0.58 and RR 0.88, 95% CI 0.79-0.97) and risperidone (RR 0.31, 95% CI 0.14-0.67 and RR 0.70, 95% CI 0.57-0.86). The incidence of extrapyramidal symptoms on paliperidone ER was comparable with other pooled SGAs (RR 0.94, 95% CI 0.66-1.35) and significantly lower than that of risperidone (RR 0.56, 0.41-0.77) but higher than that of olanzapine (RR 1.88, 95% CI 1.05-3.36). Paliperidone ER was superior to other pooled SGAs (RR 0.32, 95% CI 0.21-0.49 and RR 0.50, 95% CI 0.35-0.72) and olanzapine (RR 0.23, 95% CI 0.15-0.33 and RR 0.33, 95% CI 0.23-0.47) as far as weight gain and somnolence were concerned. Further, prolactin-related adverse events caused by paliperidone ER were comparable with other pooled SGAs (RR 1.30, 95% CI 0.73-2.33), but outnumbered those caused by olanzapine (RR 7.53, 95% CI 2.05-27.71). CONCLUSION: Paliperidone ER is efficacious, safe, and well accepted when compared with other pooled SGAs for the treatment of Chinese patients with schizophrenia.

Efficacy and safety of paliperidone extended release in adolescents with schizophrenia: a randomized, double-blind study.

OBJECTIVE: To evaluate the efficacy, safety, and tolerability of paliperidone extended release (ER) relative to aripiprazole in adolescent schizophrenia. METHOD: In this multicenter, double-blind, phase 3 study (screening [≤3 weeks], with an acute treatment period [8 weeks] and a maintenance period [18 weeks]), adolescents (12-17 years old) with schizophrenia (DSM-IV diagnosis; Positive and Negative Symptom Score [PANSS] total score 60-120) were randomized (1:1) to once-daily paliperidone ER (6 mg per day [days 1-7], flexibly dosed 3, 6, or 9 mg per day from week 2 to end of study [EOS]), or to aripiprazole (2 mg per day [days 1 and 2], 5 mg per day [days 3 and 4], 10 mg per day [days 5-7], flexibly dosed 5, 10, or 15 mg per day [week 2 to EOS]). RESULTS: Overall, 76% of enrolled patients (174/228) completed the study (paliperidone ER, 75% [85/113]; aripiprazole, 77% [89/115]). There was no significant difference in change in PANSS total scores from baseline to day 56 (primary endpoint) (paliperidone ER versus aripiprazole, -19.3 [13.80] versus -19.8 [14.56], p = .935); responders, 67.9% versus 76.3%, p = .119) and day 182 (-25.6 [16.88] versus -26.8 [18.82], p = .877; responders, 76.8% versus 81.6%, p = .444). All secondary endpoints (maintenance of clinical stability, change in PANSS-negative symptoms, Clinical Global Impression-Severity, and Personal and Social Performance scores) were similar in both treatment groups. The most common (>10% patients) treatment-emergent adverse events for paliperidone ER were akathisia, headache, somnolence, tremor, and weight gain, and for aripiprazole were worsening of schizophrenia and somnolence. Extrapyramidal symptoms including dystonia and hyperkinesia occurred in >2% in paliperidone ER-treated versus aripiprazole-treated patients. CONCLUSION: Paliperidone ER did not demonstrate superior efficacy to aripiprazole in treating adolescent schizophrenia. Both drugs showed clinically meaningful improvements in symptom and functional measurements and were generally tolerable. Clinical Trial Registration Information-An Efficacy and Safety Study of Extended-Release (ER) Paliperidone in Adolescent Participants With Schizophrenia; http://clinicaltrials.gov; NCT01009047.