Atypical Antipsychotic Paliperidone Research Articles

Inhibition of voltage-dependent K+ currents of rabbit coronary arterial smooth muscle cells by the atypical antipsychotic paliperidone.

Paliperidone, an atypical antipsychotic, is widely used to treat schizophrenia. In this study, we explored whether paliperidone inhibited the voltage-dependent K+ (Kv) channels of rabbit coronary arterial smooth muscle cells. Paliperidone reduced Kv channel activity in a concentration-dependent manner with a half-maximal inhibitory concentration (IC50 ) of 16.58 ± 3.03 μM and a Hill coefficient of 0.60 ±0.04. It did not significantly shift the steady-state activation or inactivation curves, suggesting that the drug did not affect the gating properties of Kv channels. In the presence of paliperidone, the application of 20 repetitive depolarizing pulses at 1 and 2Hz gradually increased the inhibition of the Kv current. Further, the recovery time constant after Kv channel inactivation was increased by paliperidone, indicating that it inhibited the Kv channel in a use (state)-dependent manner. Its inhibitory effects were reduced by pretreatment with a Kv1.5 subtype inhibitor. However, pretreatment with a Kv2.1 or Kv7 inhibitor did not reduce its inhibitory effect. We conclude that paliperidone inhibits Kv channels (mainly Kv1.5 subtype channels) in a concentration- and use (state)-dependent manner without changing channel gating.

A Case of Extrapyramidal Symptoms Secondary to Long-Acting Injectable Paliperidone Palmitate

Paliperidone palmitate is a long-acting injectable formulation of the atypical antipsychotic paliperidone. The once-monthly injection is approved for acute and maintenance therapy of schizophrenia in adults. Extrapyramidal symptoms are a known adverse effect of antipsychotics; incidence rates of EPS with PP are up to 18%. Given its longer half-life and steady blood levels, PP-induced EPS can cause a sustained and serious functional impairment of several months’ duration, significantly impacting the quality of life.

Treatment of substance use disorders with co-occurring severe mental health disorders.

To provide an update of treatment for substance use in patients with co-occurring substance use disorders (SUD) and mental health disorders (dual diagnosis) with a focus on both pharmacological and psychosocial interventions. A total of 1435 abstracts were identified, of which we selectively reviewed 43 for this narrative review. There is emerging evidence, both clinical and neurobiological, that clozapine is a more efficacious antipsychotic in treatment of individuals with schizophrenia and SUD. The use of depot atypical antipsychotic paliperidone palmitate in this population is also promising. Although valproate remains the treatment of choice in individuals with bipolar disorder and SUD, present evidence suggests that lithium and quetiapine may not be effective in this population. Naltrexone is the most effective anticraving agent in individuals with severe mental illness (SMI) and comorbid alcohol use disorders. The use of opioid substitution therapy in individuals with SMI and comorbid opioid use disorders is also associated with favorable outcomes. Varenicline shows promise in patients with SMI who smoke tobacco. Psychosocial interventions should be instituted early in the course of treatment. They should ideally be high intensity and based on established therapies used for SUD. The paucity of systematic studies in individuals with co-occurring mental health disorders and SUD remains a concern, given the enormous burden that they pose. However, there are a number of studies which have evaluated interventions, both psychosocial and pharmacological, which show promise and can guide clinical practice. VIDEO ABSTRACT: http://links.lww.com/YCO/A49.

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.

Valproate and paliperidone interaction

Antiepileptic drugs are frequently used in the management of psychiatric conditions, particularly bipolar disorder. Since most psychotropic agents and antiepileptic drugs share the same metabolic pathways for elimination, there is a high likelihood of interactions between these two groups of drugs. Investigators recently examined the interaction potential between valproate and the atypical antipsychotic paliperidone in healthy volunteers and in patients with psychiatric disorders.

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.

The Atypical Antipsychotic Paliperidone Regulates Endogenous Antioxidant/Anti-Inflammatory Pathways in Rat Models of Acute and Chronic Restraint Stress.

Alterations in the innate inflammatory response may underlie the pathophysiology of psychiatric diseases. Current antipsychotics modulate pro-/anti-inflammatory pathways, but their specific actions on these pathways remain only partly explored. This study was conducted to elucidate the regulatory role of paliperidone (1mg/kgi.p.) on acute (6h) and chronic (6h/day for 21 consecutive days) restraint stress-induced alterations in 2 emerging endogenous anti-inflammatory/antioxidant mechanisms: nuclear factor erythroid-related factor 2 (NRF2)/antioxidant enzymes pathway, and the cytokine milieu regulating M1/M2 polarization in microglia, analyzed at the mRNA and protein levels in prefrontal cortex samples. In acute stress conditions, paliperidone enhanced NRF2 levels, possibly related to phosphoinositide 3-kinase upregulation and reduced kelch-Like ECH-associated protein 1 expression. In chronic conditions, paliperidone tended to normalize NRF2 levels through a phosphoinositide 3-kinase related-mechanism, with no effects on kelch-Like ECH-associated protein 1. Antioxidant response element-dependent antioxidant enzymes were upregulated by paliperidone in acute stress, while in chronic stress, paliperidone tended to prevent stress-induced downregulation of the endogenous antioxidant machinery. However, paliperidone increased transforming growth factor-β and interleukin-10 in favor of an M2 microglia profile in acute stress conditions, which was also corroborated by paliperidone-induced increased levels of the M2 cellular markers arginase I and folate receptor 2. This latter effect was also produced in chronic conditions. Immunofluorescence studies suggested an increase in the number of microglial cells expressing arginase I and folate receptor 2 in the stressed animals pretreated with paliperidone. In conclusion, the enhancement of endogenous antioxidant/anti-inflammatory pathways by current and new antipsychotics could represent an interesting therapeutic strategy for the future.

Atypical antipsychotic paliperidone prevents behavioral deficits in mice prenatally challenged with bacterial endotoxin lipopolysaccharide

Studies on animal models provide enough evidences that old age appearance of psychosis on exposures to various insults during critical period of brain development could be prevented by antipsychotic drug treatment. Presently, gestational intervention of the atypical antipsychotic paliperidone (PAL) is done along with the exposure of bacterial endotoxin lipopolysaccharide/LPS hypothesizing that the drug would counteract and/or prevent the immune activation-induced behavioral deficits in mice. Effect of the PAL (0.05mg/kg; GD 15-PND 28) in preventing reflex, sensorimotor and anxiety deficits in prenatally LPS-challenged (800µg/kg; GD 15 and GD 17) mice was assessed at three different life stages: neonatal (PND 4–PND 14), adolescence (PND 35) and at adulthood (PND 85). LPS-induced behavioral deficits were recognizable even at neonatal and adolescence stages, though more pronounced at adulthood. In only PAL-treated group few behavioral deficits though observed both at neonatal and adult stages but less prominent than LPS group were found. PAL co-treatment prevented the abnormalities in nest-seeking behavior in neonates, anxiety abnormalities at adolescence and adulthood but not the sensorimotor impairment. The drug might have maintained the stress homeostasis to counteract the behavioral abnormalities as LPS-induced hypercorticosteronemia was prevented on PAL co-treatment. In view of the in utero exposure, comparatively low drug dose was selected. Though efficacy has been predicted, the dose was not effective to prevent all psychopathological impairments. Considering the wider objectives, it was not possible to conduct multi dose study simultaneously. Our ongoing study with higher dose may predict the effective PAL dose in prevention of psychiatric illness.

PMH34 - Cost-Effectiveness of Paliperidone Palmitate for the Treatment of Schizophrenia in Germany

Treatment with antipsychotic medication is an important element of relapse prevention in the management of schizophrenia, and can reduce inpatient stays. Recently, the long-acting atypical antipsychotic paliperidone long-acting injectable (PLAI), a once-monthly LAI antipsychotic, was approved for treatment of schizophrenia in Germany. To estimate, based on a previously published model, the cost effectiveness of PLAI compared with other common antipsychotic treatment strategies in patients diagnosed with schizophrenia in Germany. A Markov decision analytic model was adapted to the German healthcare system. The model considers the cost effectiveness for PLAI as a maintenance treatment for patients with schizophrenia from the payer perspective. The patients transition between eight health states on a monthly basis over a 5-year time horizon. As therapeutic strategies, PLAI, quetiapine, risperidone long-acting injections (RLAI), oral olanzapine, oral risperidone, zuclopenthixol decanoate, olanzapine long-acting injections (OLAI), oral typical and oral atypical were compared. Probability of relapse, level of adherence, side effects and treatment discontinuation were derived from the Swedish original model. Input factors regarding resource use and costs were estimated and adjusted for the German healthcare system. A probabilistic sensitivity analyses (PSA) using cost-effectiveness scatter plots was performed to visualize the robustness of the results. In base-case scenario, PLAI is superior to RLAI in gained quality-adjusted life-years (QALYs) and avoided relapses. Relative to all other treatment strategies, PLAI is more effective with regard to gained QALYs and avoided relapses but results in higher treatment costs over a 5-year horizon in base-case scenario. The results were tested in PSA. If a cost-effectiveness threshold of €30,000 is assumed, for example, PLAI can be considered to be cost effective compared with RLAI in about 92.5 % of cases regarding gained QALYs, and in 78.6 % of cases regarding avoided relapse. Compared with OLAI, in about 94.4 % of cases regarding gained QALYs and in 99.9 % of cases regarding avoided relapse, cost effectiveness can be considered. Comparing PLAI and zuclopenthixol decanoate, cost effectiveness can be assumed in about 90.4 % of cases regarding gained QALYs, and in all cases regarding avoided relapse. PLAI dominates RLAI and compared with the other treatment strategies PLAI has shown to be more effective but results in higher costs in base-case scenario.

Cost Effectiveness of Paliperidone Palmitate for the Treatment of Schizophrenia in Germany

Treatment with antipsychotic medication is an important element of relapse prevention in the management of schizophrenia, and can reduce inpatient stays. Recently, the long-acting atypical antipsychotic paliperidone long-acting injectable (PLAI), a once-monthly LAI antipsychotic, was approved for treatment of schizophrenia in Germany. To estimate, based on a previously published model, the cost effectiveness of PLAI compared with other common antipsychotic treatment strategies in patients diagnosed with schizophrenia in Germany. A Markov decision analytic model was adapted to the German healthcare system. The model considers the cost effectiveness for PLAI as a maintenance treatment for patients with schizophrenia from the payer perspective. The patients transition between eight health states on a monthly basis over a 5-year time horizon. As therapeutic strategies, PLAI, quetiapine, risperidone long-acting injections (RLAI), oral olanzapine, oral risperidone, zuclopenthixol decanoate, olanzapine long-acting injections (OLAI), oral typical and oral atypical were compared. Probability of relapse, level of adherence, side effects and treatment discontinuation were derived from the Swedish original model. Input factors regarding resource use and costs were estimated and adjusted for the German healthcare system. A probabilistic sensitivity analyses (PSA) using cost-effectiveness scatter plots was performed to visualize the robustness of the results. In base-case scenario, PLAI is superior to RLAI in gained quality-adjusted life-years (QALYs) and avoided relapses. Relative to all other treatment strategies, PLAI is more effective with regard to gained QALYs and avoided relapses but results in higher treatment costs over a 5-year horizon in base-case scenario. The results were tested in PSA. If a cost-effectiveness threshold of <euro>30,000 is assumed, for example, PLAI can be considered to be cost effective compared with RLAI in about 92.5 % of cases regarding gained QALYs, and in 78.6 % of cases regarding avoided relapse. Compared with OLAI, in about 94.4 % of cases regarding gained QALYs and in 99.9 % of cases regarding avoided relapse, cost effectiveness can be considered. Comparing PLAI and zuclopenthixol decanoate, cost effectiveness can be assumed in about 90.4 % of cases regarding gained QALYs, and in all cases regarding avoided relapse. PLAI dominates RLAI and compared with the other treatment strategies PLAI has shown to be more effective but results in higher costs in base-case scenario.

Poster #186 EFFECTIVENESS VS EFFICACY RANKINGS BY A MODIFIED PRECIS TOOL FOR SCHIZOPHRENIA TRIALS OF LONG-ACTING INJECTABLE VS DAILY ORAL ANTIPSYCHOTIC TREATMENTS

We assessed efficacy and tolerability of the injectable atypical antipsychotic paliperidone palmitate in delaying time-to-relapse in adults with schizophrenia.Eligible patients (Positive and Negative Syndrome Scale [PANSS] total score < 120) were transitioned from previous antipsychotics to paliperidone palmitate during a 9-week, open-label phase. Patients received the first 2 intramuscular injections of paliperidone palmitate (50 mg eq) one-week apart, then subsequent injections (25, 50, or 100 mg eq, flexibly-dosed), once-monthly. Stable patients (PANSS total score ≤ 75) continued into the 24-week maintenance phase. At maintenance phase endpoint, stabilized patients were randomized (1:1 ratio) to either continue paliperidone palmitate (at stabilized dose) or begin placebo in the variable-duration, double-blind phase.The preplanned interim analysis (conducted after 68 relapse events) included 312 patients: mean age = 40 years, 55% men, 66% white, and mean transition baseline PANSS total score (SD): placebo, 69.5 (16.89); paliperidone palmitate, 69.3 (17.39). Time-to-relapse (primary endpoint) favored paliperidone palmitate (p < 0.0001, log-rank test) at interim and final analysis (n = 408). The hazard ratio (placebo/paliperidone palmitate) at the final analysis was 3.60 (95% CI: 2.45, 5.28). Treatment-emergent adverse event rates (final analysis set) were: 67% for transition and maintenance phases, and 45% (placebo) and 44% (paliperidone palmitate) for the double-blind phase. Across phases, the incidence of glucose-related adverse events was low (≤ 4%), while mean weight increased by 1.9 kg for paliperidone palmitate and remained unchanged for placebo patients. Injection site tolerability was comparable between groups.Paliperidone palmitate significantly delayed time-to-relapse compared with placebo and presented no new safety signals.

Anaphylactoid reaction to paliperidone palmitate extended-release injectable suspension in a patient tolerant of oral risperidone

A probable anaphylactoid reaction to the injectable formulation of the atypical antipsychotic paliperidone in a patient with established tolerability to oral risperidone is reported. A 19-year-old man with schizophreniform disorder was admitted to the emergency department experiencing command hallucinations and persecutory delusions. The patient was treated with oral risperidone during which time his presenting symptoms improved; no risperidone-related adverse effects were noted. Due to concerns about long-term adherence to daily risperidone use, it was decided to initiate once-monthly injections of paliperidone palmitate extended-release suspension. Within 15 minutes of the first paliperidone injection, the patient developed flushing of the face, neck, and head, and he soon developed chills, rigors, and difficulty breathing; after treatment to resolve those symptoms, oral risperidone was restarted. No further drug-related problems occurred during the man's hospital stay. The pharmacy subsequently received notice that the medication lot from which the patient had received the paliperidone dose had been recalled due to reports of cracked syringes, but a possible link between the syringe defect and the man's anaphylactoid symptoms could not be determined. The temporal relationship between paliperidone palmitate administration and the onset of the man's symptoms, as well as application of the Naranjo nomogram, indicated a probable anaphylactoid reaction associated with the paliperidone formulation. A man who had tolerated oral risperidone developed an anaphylactoid reaction after receiving an injection of paliperidone palmitate extended-release suspension. After recovering from the reaction, the patient again received oral risperidone without adverse effects.

Lithium, but Not Fluoxetine or the Corticotropin-Releasing Factor Receptor 1 Receptor Antagonist R121919, Increases Cell Proliferation in the Adult Dentate Gyrus

Several antidepressant drugs have previously been reported to increase neurogenesis in the dentate gyrus of the hippocampus in laboratory animals. We found no effect of the selective serotonin reuptake inhibitor fluoxetine or the corticotropin-releasing factor receptor 1 antagonist R121919 [3-[6-(dimethylamino)-4-methylpyridin-3-yl]-2,5-dimethyl-N,N-dipropyl-1H-pyrazolo[1,5-a]pyrimidin-8-ium-7-amine] on the rate of cell proliferation or hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression in either adult or adolescent rats after long-term administration. In adults, the mood stabilizer lithium was found to significantly increase cell proliferation; the atypical antipsychotic paliperidone did not affect proliferation, either alone or when combined with lithium. Fourteen-day survival of neuronally fated cells showed a significant interaction effect of lithium and paliperidone but no effect of either drug alone. BDNF mRNA expression was significantly decreased by lithium in the CA1/2 cell fields and increased by paliperidone in the CA1/2, CA3, and dentate gyrus. These results raise questions concerning the hypothesis that all antidepressants increase neurogenesis under nonstressed conditions. They also confirm and extend previous reports of lithium-induced increases in cell proliferation but not survival.

A double-blind study of paliperidone palmitate and risperidone long-acting injectable in adults with schizophrenia

This 13-week double-blind study was designed to assess noninferiority of the recently approved (in the U.S.) injectable atypical antipsychotic paliperidone palmitate (PP) versus risperidone long-acting injectable (RIS-LAI) in adult patients with schizophrenia. Patients (N=1220) were randomized (1:1) to either a) PP: deltoid injections on day 1 (150 mg eq.), day 8 (100 mg eq.), and once-monthly flexible dosing as deltoid or gluteal injections on day 36 (50 mg eq. or 100 mg eq.) and day 64 (50 mg eq. or 100 mg eq. or 150 mg eq.) or b) RIS-LAI: gluteal injections days 8 and 22 (25mg), days 36, 50 (25 or 37.5mg) and days 64, 78 (25, 37.5 or 50mg). RIS-LAI-treated patients received oral supplementation with RIS 1-6 mg/day (days 1 to 28), and PP-treated patients received oral placebo. The safety analysis set (n=1214) included 58% men, 78% white, with mean (SD) baseline PANSS total score: PP, 84.1 (12.09); and RIS-LAI, 83.6 (11.28). Mean (SD) change from baseline to endpoint in PANSS total score decreased similarly in both groups; PP (-18.6 [15.45]) and RIS-LAI (-17.9 [14.24]). PP treatment was noninferior to RIS-LAI (point estimate [95% CI]: 0.4 [-1.62;2.38], per-protocol analysis set [primary analysis]). The tolerability and safety of PP was generally similar to RIS-LAI with no new safety or tolerability findings.

Efficacy and safety of paliperidone palmitate in adult patients with acutely symptomatic schizophrenia: a randomized, double-blind, placebo-controlled, dose-response study

This 13-week, double-blind study evaluated the efficacy and safety of the atypical antipsychotic paliperidone palmitate (recently approved in the United States) versus placebo administered as monthly gluteal injections (after two initial doses given 1 week apart) in acutely symptomatic patients with schizophrenia. Patients (N=388) were randomly assigned (1 : 1 : 1 : 1) to paliperidone palmitate 50, 100, or 150 mg eq. or placebo. As the 150 mg eq. dose was administered to fewer patients (n=30) than planned, meaningful and definitive conclusions cannot be drawn from the results of this group. The change from baseline in Positive and Negative Syndrome Scale total score at endpoint showed improvement in both paliperidone palmitate 50 and 100 mg eq. groups but was significant only in the 100 mg eq. group (P=0.019). The paliperidone palmitate 50 (P=0.004) and 100 mg eq. (P<0.001) groups showed significant improvement in the Personal and Social Performance score from baseline to endpoint versus placebo. Common adverse events (in >or=2% of patients in any group) more frequent with paliperidone palmitate 50 or 100 mg eq. than placebo (>or=5% difference) were headache, vomiting, extremity pain, and injection site pain. Treatment with paliperidone palmitate (100 mg eq.) was efficacious and all doses tested were tolerable.

A Randomized, Placebo-Controlled Study to Assess the Efficacy and Safety of 3 Doses of Paliperidone Palmitate in Adults With Acutely Exacerbated Schizophrenia

This study assessed the efficacy and the safety of a dosing regimen that was revised from earlier studies for the investigational injectable atypical antipsychotic paliperidone palmitate (approved in the USA, August 2009) for adult patients with acutely exacerbated schizophrenia. The patients (N = 652) were randomly assigned (1:1:1:1) to paliperidone palmitate at 25, 100, or 150 mg eq. or placebo in this 13-week double-blind study. The patients received an injection of paliperidone palmitate at 150 mg eq. or placebo in the deltoid muscle on day 1 and the assigned fixed dose or placebo in the deltoid or gluteal [corrected] on day 8 and then once monthly (days 36 and 64). No oral supplementation was used. Target plasma levels were achieved by day 8 in all paliperidone palmitate groups. The mean change in Positive and Negative Syndrome Scale total score from baseline to end point improved significantly (P < or = 0.034) in all the paliperidone palmitate dose-groups versus placebo. Paliperidone palmitate treatment with this revised dosing regimen led to the achievement of rapid and consistent therapeutically effective plasma levels that were maintained by once-monthly dosing in either the deltoid or gluteal muscle. Common treatment-emergent adverse events (> or =2% of patients in any of the treatment groups) that occurred more frequently in the total paliperidone palmitate group versus the placebo group (with > or =1% difference) were injection-site pain (7.6% vs 3.7%), dizziness (2.5% vs 1.2%), sedation (2.3% vs 0.6%), pain in the extremity (1.6% vs 0.0%), and myalgia (1.0% vs 0.0%). The paliperidone palmitate treatment was efficacious and generally tolerated across the dose range (25, 100, or 150 mg eq.) in adult patients with acutely exacerbated schizophrenia.

Sekundärdaten für Budget Impact Analysen

Budget impact analyses are performed to estimate the possible influence of a new health-care technology on the available budget. Scenarios should be if at all possible, evidence-based assumptions on the proportion of treated patients, the current and future mix as well as the direct costs of treatment. For the example of the atypical antipsychotic paliperidone, it is demonstrated that secondary data from routine health-care are well suited for this purpose. By means of the IMS database Disease Analyzer, which consists of the electronic records of a nation-wide representative panel of German physicians (family doctors/general practitioners and neurologists/pschiatrists), various subgroups of schizophrenia patients were identified and the composition and costs of antipsychotic therapy determined in a retrospective longitudinal or, respectively, cross-sectional analysis. The demographic data were obtained via the patient records from the offices of 895 general practitioners/family doctors and 102 neurologists/psychiatrists. The number of ill and treated patients with schizophrenia (N=7 927) was determined from the diagnoses and prescriptions. By means of the prescription data (substance and form of administration) the treatment mix was defined. Total costs (2.7 million Euro in 2008) for the antipsychotic therapy were evaluated by links in the databank between individual prescription and the exact monthly pricelists of the pharmacy. With the example of a budget impact analysis for the atypical antipsychotic paliperidone ER it was shown that the specific secondary data of the IMS Disease Analyzers are suitable to set up an evidence-based, comprehensive model.

The effect of combination treatment by paliperidone and psychological intervention on first-episode schizophrenic out-patient

Objective To evaluate the effect of combination treatment by psychological intervention and a new atypical antipsychotic Paliperidone extended-release tablets(paliperidone ER)on first-episode schizophrenic out-patients.Methods All 62 patients diagnosed as first-episode schizophrenia by DSM-Ⅳ were randomly allocated into,combination treatment group and control group,for a 12-month treatment study.The combination treatment group was treated by paliperidone ER once a day and psychological counseling once a month,while the control group was treated only by paliperidone ER.The efficacy and social function were assessed by Positive and Negative Syndrome Scale(PANSS)and Personal and Social Performance Scale(PSP)individually at baseline,and following 1,3,6,9,12 months.The remission rate was calculated at the end of the 3rd,6th,9th month.The safety and tolerability were assessed using Barnes Akathisia Scale(BARS),extrapyramidal side effects scale(SAS)and involuntary movement scale(AIMS).Results Twenty-seven patients of combination treatment group and seventeen patients of the control group completed the trial with the discontinuation rate 12.9% and 45.2%,respectively.The difference between the above two groups was statistically significant(P＜0.05).The mean total score of PANSS and the PSP of the both groups were significantly improved(P＜0.05)after treatment.PANSS total score reduced more than 30% compared with baseline,and PSP total score increased more than 7.The remission rate of combination treatment group was 74.2%,51.6% and 67.7% at the end of 3rd,6th,and 9th month,which was better than the control group(45.2%,38.7% and 38.7%)(P＜0.05).Both incidence and types of adverse events were almost same between the two groups.The major adverse events were extrapyramidal symptoms,tachycardia,gastrointestinal discomfort and akathisia.Conclusion Paliperidone ER treatment combined with psychological intervention on first-episode schizophrenia out-patients can improve their treatment compliance by reducing the discontinuation rate.And this combination treatment can increase the remission rate and improve social functioning of the patients. Key words: Schizophrenia; Psychological intervention; Paliperidone; Remission rate; Social Functioning

Paliperidone palmitate maintenance treatment in delaying the time-to-relapse in patients with schizophrenia: A randomized, double-blind, placebo-controlled study

Objective We assessed efficacy and tolerability of the injectable atypical antipsychotic paliperidone palmitate in delaying time-to-relapse in adults with schizophrenia. Methods Eligible patients (Positive and Negative Syndrome Scale [PANSS] total score < 120) were transitioned from previous antipsychotics to paliperidone palmitate during a 9-week, open-label phase. Patients received the first 2 intramuscular injections of paliperidone palmitate (50 mg eq) one-week apart, then subsequent injections (25, 50, or 100 mg eq, flexibly-dosed), once-monthly. Stable patients (PANSS total score ≤ 75) continued into the 24-week maintenance phase. At maintenance phase endpoint, stabilized patients were randomized (1:1 ratio) to either continue paliperidone palmitate (at stabilized dose) or begin placebo in the variable-duration, double-blind phase. Results The preplanned interim analysis (conducted after 68 relapse events) included 312 patients: mean age = 40 years, 55% men, 66% white, and mean transition baseline PANSS total score (SD): placebo, 69.5 (16.89); paliperidone palmitate, 69.3 (17.39). Time-to-relapse (primary endpoint) favored paliperidone palmitate ( p < 0.0001, log-rank test) at interim and final analysis ( n = 408). The hazard ratio (placebo/paliperidone palmitate) at the final analysis was 3.60 (95% CI: 2.45, 5.28). Treatment-emergent adverse event rates (final analysis set) were: 67% for transition and maintenance phases, and 45% (placebo) and 44% (paliperidone palmitate) for the double-blind phase. Across phases, the incidence of glucose-related adverse events was low (≤ 4%), while mean weight increased by 1.9 kg for paliperidone palmitate and remained unchanged for placebo patients. Injection site tolerability was comparable between groups. Conclusion Paliperidone palmitate significantly delayed time-to-relapse compared with placebo and presented no new safety signals.