Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated the efficacy of paliperidone extended-release (ER), an investigational psychotropic agent, in delaying symptom recurrence in adult patients with schizophrenia and its safety and tolerability. In this randomized, double-blind, placebo-controlled, multicenter study, patients' symptoms were stabilized during an 8-week run-in and a 6-week stabilization phases using open-label, flexibly dosed paliperidone ER (3-15 mg once daily, starting dose = 9 mg). The primary efficacy variable was the time of first recurrence of schizophrenia symptoms, which included predefined changes in symptom scores, psychiatric hospitalization, self-injury, and suicidal or aggressive behavior during the double-blind phase (paliperidone ER or placebo treatment). Based on positive efficacy, the study was terminated at the preplanned interim analysis (43 recurrence events). The interim analysis (primary analysis) included 113 patients (mean age = 41 years; 51% men, 85% white). In the intent-to-treat group, 14 paliperidone ER-treated patients (25%) experienced a recurrence event versus 29 (53%) for placebo. Time-to-recurrence was significantly different, favoring the paliperidone ER group (P = 0.005, log-rank test): 25% quantile of time-to-recurrence was 83 days (paliperidone ER) versus 23 days (placebo). Final analyses (n = 205) were confirmatory. During initial open-label treatment with paliperidone ER, symptoms improved significantly. This improvement was maintained with continued treatment, as were functioning and quality-of-life measures. Treatment-emergent adverse events rates were similar: 35% for paliperidone ER and 40% for placebo. Paliperidone ER treatment versus placebo significantly delayed time-to-recurrence in patients with schizophrenia, maintained symptom stability and measures of functioning, and was generally well tolerated in this patient population.
 ...
PMID:Paliperidone extended-release tablets for prevention of symptom recurrence in patients with schizophrenia: a randomized, double-blind, placebo-controlled study. 1722 6

Paliperidone, the 9-hydroxy metabolite of risperidone, was approved on 20 December, 2006 by the US Food and Drug Administration for the treatment of schizophrenia. It is also being tested for the treatment of bipolar mania. An on-line query of http://www.pubmed.gov and http://www.clinicaltrials.gov for 'paliperidone' and '9-hydroxy-risperidone' was done, along with an examination of poster presentations at scientific meetings held in 2006. Three 6-week pivotal clinical trials of paliperidone extended-release at fixed doses ranging from 3 to 15 mg administered orally once daily in the treatment of acute schizophrenia demonstrated superior efficacy to placebo. A favourable tolerability profile was also evidenced, except for prolactin elevation and dose-related extra-pyramidal effects. A relapse prevention study provides evidence of superiority of paliperidone over placebo in the maintenance of response. Safety has also been assessed in patients with schizophrenia who are 65 years or older. At present there are no studies available that are powered to directly compare paliperidone to other second-generation antipsychotics, including risperidone. With the impending availability of oral risperidone as a generic medication, cost of oral paliperidone will likely become a significant obstacle to its use.
 ...
PMID:Paliperidone: quo vadis? 1734 60

Paliperidone extended release (ER) is an atypical antipsychotic that is administered orally once daily to provide consistent plasma drug concentrations over 24 hours in adult patients with schizophrenia. In four well controlled trials, once-daily administration of paliperidone ER 3-12 mg over 6 weeks was more effective than placebo in reducing the positive and negative symptoms experienced by adult patients with schizophrenia, including elderly individuals aged > or =65 years. Patients with schizophrenia treated with paliperidone ER achieved greater improvement in clinically relevant measures of personal and social functioning and disease severity than those who received placebo. In another well controlled trial, paliperidone ER demonstrated superior efficacy to placebo in preventing the recurrence of schizophrenia symptoms. In patients who experienced a recurrence, time to recurrence was delayed with paliperidone ER compared with placebo administration.black triangle Paliperidone ER 3-12 mg/day for 6 weeks was generally well tolerated by patients with schizophrenia in clinical trials.
 ...
PMID:Paliperidone extended release. 1744 29

Extended-release paliperidone is a new atypical antipsychotic chemically related to the well-known antipsychotic risperidone. It has been formulated in an osmotic controlled-release oral delivery system that minimizes peak-trough fluctuations and, by obviating dose-titration, allows once-daily dosing with a therapeutically active dose from the first day. Its pharmacokinetic profile is characterized by a mean time-to-peak plasma concentration of 24.1 hours and an elimination half-life of approximately 24 hours. A dose of 6 mg of paliperidone extended-release (ER) provides a mean striatal D2 receptor occupancy of 64%, approaching the accepted lower receptor occupancy threshold required for optimal antipsychotic activity without causing extrapyramidal symptoms. It undergoes minimal hepatic biotransformation and is mainly excreted unchanged in the urine with four metabolic products. Three pivotal randomized, double-blind, placebo-controlled, parallel-group six-week trials investigated the efficacy, safety and tolerability of paliperidone ER at doses of 3-15 mg/day. All doses produced a significant reduction in schizophrenia symptomatology, with an onset of effect as of day 4. Personal and social functioning also improved as measured by the Personal and Social Performance scale. A prevention of recurrence study showed that paliperidone ER effectively prolonged the time-to-recurrence versus placebo. Paliperidone ER was efficacious in young, elderly and recently diagnosed schizophrenia patients. Beneficial effects on sleep assessed objectively and subjectively with minimal daytime somnolence were demonstrated. Overall, it was well-tolerated and had placebo-like discontinuation rates for adverse events. There were some dose-related extrapyramidal symptoms, mostly mild to moderate in intensity and associated with minimal changes in the rating scales that assessed extrapyramidal symptom severity. Although prolactin elevation occurred with paliperidone ER, only few prolactin-related adverse events were reported. There were no signals for metabolic dysfunction in terms of glucose, insulin, lipid or triglyceride changes or any indicators of clinically relevant cardiac events. Body weight increased slightly, but the changes were acceptable in the context of the doses likely to be used clinically, and patients with higher initial body mass index gained less weight as has been reported for other antipsychotics.
 ...
PMID:Extended-release paliperidone: efficacy, safety and tolerability profile of a new atypical antipsychotic. 1746 Jul 86

The effects of paliperidone extended-release on sleep architecture in patients with schizophrenia-related insomnia were evaluated in this multicenter, double-blind, randomized, placebo-controlled study. Patients received paliperidone extended-release 9 mg/day or matching placebo during the 14-day double-blind phase. Sleep architecture and sleep continuity were evaluated using polysomnograms. Subjective sleep measures were evaluated daily using the Leeds Sleep Evaluation Questionnaire. Efficacy and safety were also assessed. Thirty-six patients (17 on paliperidone extended-release, 19 on placebo; mean age 32.2 years) completed the study. Paliperidone extended-release treatment vs. placebo resulted in clinically and statistically significant differences in sleep measurements from baseline to endpoint including a reduction in: persistent sleep latency (41 min), sleep onset latency (35 min), number of awakenings after sleep onset (7), time awake in bed (50 min), and stage 1 sleep duration (12 min); prolongation in: total sleep time (53 min), sleep period time (42 min), stage 2 sleep duration (51 min), and rapid eye movement sleep duration (18 min); and an increase in sleep efficiency index (11%). Paliperidone extended-release, compared with placebo, did not exacerbate daytime somnolence and improved symptoms of schizophrenia. Paliperidone extended-release was well tolerated and improved sleep architecture and sleep continuity in patients diagnosed with schizophrenia and concomitant insomnia.
 ...
PMID:A double-blind, placebo-controlled, randomized study evaluating the effect of paliperidone extended-release tablets on sleep architecture in patients with schizophrenia. 1769 May 99

Paliperidone extended release (ER) is the most recent atypical antipsychotic to become available for the treatment of schizophrenia. It has a unique extended-release delivery system, allowing once/day dosing with steady plasma concentrations of the medication. Several randomized, double-blinded, placebo-controlled trials have shown paliperidone ER to be efficacious in the management of acute schizophrenia as well as for the prevention of symptom recurrence when compared with placebo. Patients in the treatment groups receiving daily doses ranging from 3 to 12 mg displayed generalized symptom improvement using the Positive and Negative Syndrome Scale (PANSS) and improved functioning on the Personal and Social Performance Scale. Paliperidone ER has been shown to be generally safe and tolerable. At its recommended dose of 6 mg daily, the reported extrapyramidal symptom adverse events are similar to placebo, and weight gain is very modest. However, at higher doses, weight gain and extrapyramidal symptoms are more elevated. Paliperidone ER has the potential to offer advantages over its parent compound and other second generation agents, and may aid in ensuring compliance among persons with schizophrenia. At present, there are no published data from a comparative trial with paliperidone ER versus its parent compound or other second-generation antipsychotic agents.
 ...
PMID:Paliperidone: a new extended-release oral atypical antipsychotic. 1792 85

Paliperidone extended-release (ER) is a newly commercialised antipsychotic formulated using the principal active metabolite of risperidone, 9-hydroxyrisperidone. It has been developed as an osmotic controlled-release oral delivery system that minimizes peak-trough fluctuations in plasma concentrations, allowing once-daily administration and theoretically leading to a decreased incidence of adverse effects. Available data from preregistration, multicenter, short-term, double-blind, placebo-controlled studies indicate that paliperidone ER, at dosages of 3-15 mg/day, is relatively safe and well tolerated in adult patients with schizophrenia. As with risperidone, paliperidone may cause extrapyramidal symptoms and hyperprolactinemia in a dose-dependent manner. Preliminary long-term studies (up to 52 weeks) appear to confirm the findings from short-term trials indicating a low liability for paliperidone ER to cause metabolic effects (i.e., weight gain, hyperglycaemia and lipid dysregulation). Safety data from elderly patients appear to be promising. Due to negligible hepatic biotransformation, paliperidone ER is unlikely to be involved in clinically significant metabolic drug-drug interactions.
 ...
PMID:The pharmacology and safety of paliperidone extended-release in the treatment of schizophrenia. 1796 54

(1) For patients with schizophrenia, risperidone is one of many available neuroleptics. It has no tangible advantages over conventional neuroleptics such as haloperidol. (2) Paliperidone, the main active metabolite of risperidone, has now arrived on the European market, in the form of sustained-release osmotic tablets. Clinical evaluation is based on 3 placebo-controlled trials lasting 6 weeks. As expected, paliperidone was effective in relieving symptoms of schizophrenia. However, it was no more effective than olanzapine and has not been compared with risperidone. (3) The adverse effect profile of paliperidone in these trials was predictable, consisting mainly of short-term neurological effects and dose-dependent weight gain. Paliperidone also provokes tachycardia and lengthens the QT interval in some patients. The rigid osmotic tablets can cause gastrointestinal complications. (4) Paliperidone does not represent a therapeutic advance. It is better to continue using a conventional neuroleptic such as haloperidol.
 ...
PMID:Paliperidone: new drug. Just a metabolite of risperidone, a neuroleptic soon off-patent. 1809

Paliperidone-extended release (ER) is an antipsychotic medication newly introduced in the USA and Europe in 2007. It is the first oral atypical antipsychotic with an extended release, which is achieved by the osmotic-controlled release oral delivery system (OROS), a well-established technology already in use for CNS drugs (e.g., methylphenidate and hydromorphone). Paliperidone was in the focus of investigations for years, as it is the major metabolite (9-hydroxyrisperidone) of the widely used atypical antipsychotic risperidone. Paliperidone-ER has demonstrated clinical efficacy, safety and good tolerability on a once-daily basis in three randomized, double-blind, placebo-controlled, 6-week-studies including patients with acute schizophrenia and one randomized, double-blind, placebo-controlled long-term study assessing recurrence of psychotic symptoms in patients with schizophrenia. Key features are predominant renal elimination, therefore low risk of interaction with other drugs, good efficacy against psychotic symptoms based on D2-receptor and 5HT2A-receptor antagonism and very low affinity for muscarinic receptors resulting in absence of anticholinergic side effects. The OROS-ER technology leads to considerably lower plasma peak levels compared with nonextended-release formulations, thus possibly reducing side effects.
 ...
PMID:Paliperidone-ER: first atypical antipsychotic with oral extended release formulation. 1827 6

Paliperidone, the major active metabolite of risperidone (9-hydroxyrisperidone), is a second-generation antipsychotic that was recently approved by the United States Food and Drug Administration for treatment of acute schizophrenia and for maintenance treatment of schizophrenia. We performed a literature search of PreMEDLINE, MEDLINE, and International Pharmaceutical Abstracts from 1966-October 2007 to review the available data on the pharmacology, pharmacokinetics, clinical evidence, and safety and tolerability profile of paliperidone extended-release (ER). Articles from randomized controlled trials, abstracts, and posters presented at national scientific meetings were included in this review. Paliperidone ER has been shown to be significantly more effective in improving schizophrenic symptoms according to the Positive and Negative Symptom Scale (PANSS), Clinical Global Impressions-Severity Scale, and Personal and Social Performance Scale compared with placebo (p<0.05). In addition, limited evidence suggests similar efficacy between paliperidone ER 6-12 mg/day and risperidone 4-6 mg/day. A 2-week, double-blind comparison with quetiapine demonstrated that paliperidone ER was significantly better than quetiapine in improving PANSS scores (p<0.001). Paliperidone ER appears to be well tolerated at the recommended starting dosage of 6 mg/day. The most commonly reported adverse effect was dose-related extrapyramidal symptoms. Weight gain and metabolic disturbances were minimal. The cost of paliperidone ER appears to be slightly higher than that of other second-generation antipsychotics. Paliperidone ER tablets may be a safe and effective treatment option for acute schizophrenia and maintenance treatment of schizophrenia compared with placebo. Because well-designed comparative data are lacking, an additional benefit over other antipsychotics is yet to be determined.
 ...
PMID:Paliperidone extended-release for the treatment of schizophrenia. 1882 23


1 2 3 4 5 6 7 8 Next >>