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Distribution by Scientific Domains


Selected Abstracts


Multicenter, randomized, double-blind, active comparator and placebo-controlled trial of a corticotropin-releasing factor receptor-1 antagonist in generalized anxiety disorder,

DEPRESSION AND ANXIETY, Issue 5 2010
Vladimir Coric M.D.
Abstract Background: Antagonism of corticotropin-releasing factor (CRF) receptors has been hypothesized as a potential target for the development of novel anxiolytics. This study was designed to determine the safety and efficacy of pexacerfont, a selective CRF-1 receptor antagonist, in the treatment of generalized anxiety disorder (GAD). Method: This was a multicenter, randomized, double-blind, placebo-controlled and active comparator trial. Two hundred and sixty patients were randomly assigned to pexacerfont 100,mg/day (after a 1 week loading dose of 300,mg/day), placebo or escitalopram 20,mg/day in a 2:2:1 ratio. The primary outcome was the mean change from baseline to end point (week 8) in the Hamilton Anxiety Scale total score. Results: Pexacerfont 100,mg/day did not separate from placebo on the primary outcome measure. The half-powered active comparator arm, escitalopram 20,mg/day, demonstrated efficacy with significant separation from placebo at weeks 1, 2, 3, 6, and 8 (P<.02). Response rates for pexacerfont, placebo, and escitalopram were 42, 42, and 53%, respectively. Genetic and psychometric rating scale data was obtained in 175 randomized subjects. There was a significant association between a single nucleotide polymorphism (SNP) of the gene encoding plexin A2 (PLXNA2-2016) with the HAM-A psychic subscale score for the entire cohort at baseline (FDR-adjusted P=.015). Conclusions: Pexacerfont did not demonstrate efficacy compared to placebo for the treatment of GAD. Whether these findings are generalizable to this class of agents remains to be determined. Our preliminary genetic finding of an association between a SNP for the gene encoding plexin A2 and an anxiety phenotype in this study merits further exploration. The trial was registered at clinicaltrials.gov (NCT00481325) before enrollment. Depression and Anxiety, 2010. © 2010 Wiley-Liss, Inc. [source]


Paliperidone palmitate , review of the efficacy, safety and cost of a new second-generation depot antipsychotic medication

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2 2010
L. Citrome
Summary Objective:, To describe the efficacy, safety and cost of paliperidone palmitate, a depot antipsychotic medication recently approved for the treatment of schizophrenia. Data sources:, A literature search was conducted by querying the websites http://www.pubmed.gov, http://www.fda.gov, http://www.accessdata.fda.gov/scripts/cder/drugsatfda and http://www.clinicaltrials.gov for the search term ,paliperidone palmitate'. Cost information was obtained from the pharmaceutical vendor servicing a local state-operated psychiatric facility. Study selection:, All available reports of studies were identified. Product labelling provided additional information. Data extraction:, Descriptions of the principal results and calculation of the number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the study reports and synopses. Additional safety outcomes subject to NNH analysis were obtained from product labelling. Data synthesis:, Paliperidone palmitate is a newly available depot formulation of paliperidone (the 9-OH metabolite of risperidone). Upon injection into the deltoid or gluteal muscle, the release of the drug starts as early as day 1, reaches maximum plasma concentrations at 13 days and lasts for as long as 126 days. Maximum concentration following deltoid injection is approximately 28% higher compared with injection into the gluteal muscle, and thus paliperidone palmitate requires initiation by two initial deltoid injections spread 1 week apart to achieve therapeutic concentrations rapidly. Subsequent injections are at 4-week intervals. Acute efficacy was evidenced by four short-term double-blind, randomised, placebo-controlled, fixed-dose studies of acutely relapsed adult inpatients who met DSM-IV criteria for schizophrenia. NNT for a 30% or greater decrease in the Positive and Negative Syndrome Scale total score compared with placebo was consistently lower for the higher dose strengths of 156 and 234 mg, suggesting a therapeutic dose,response. Treatment with paliperidone palmitate at doses between 39 and 156 mg significantly delayed the time to recurrence of symptoms of schizophrenia after 24 weeks of maintained symptom stability. The NNT vs. placebo to avoid a recurrence of symptoms was 5 (95% CI 4,7). Overall, paliperidone palmitate was reasonably well tolerated, with low rates of extrapyramidal symptoms or body weight gain; however, these may be more common at higher doses. Injection site reactions occurred at a rate ranging from 4% to 10%, depending on the dose regimen, compared with 2% for the pooled placebo arms. The acquisition cost of a maintenance dose of paliperidone palmitate calculated on a per day basis is similar to that for risperidone microspheres, but about double the cost for oral paliperidone and approximately 19 times the cost of oral generic risperidone. Conclusions:, Paliperidone palmitate is efficacious for the acute and maintenance treatment of schizophrenia and is reasonably well tolerated. It offers several advantages over other available second-generation depot antipsychotics: it comes in prefilled syringes in a number of different dosage strengths; it does not require refrigeration; it does not require supplementation with oral antipsychotics; it can be administered once monthly; it can be administered with a very small bore needle; the injection volume is small; the injection site can be either the deltoid or gluteal muscles; it does not require an additional precautionary observation period after the injection. For patients for whom oral risperidone or paliperidone is otherwise effective, paliperidone palmitate offers a guaranteed delivery system that enhances adherence. However, the high acquisition cost of paliperidone palmitate will likely be an important obstacle to its routine use. [source]


Clinical predictors of response to pharmacotherapy with selective serotonin reuptake inhibitors in obsessive,compulsive disorder

PSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 4 2006
IT TÜKEL md
Abstract, The objective of this study was to investigate the clinical predictors of response to treatment with selective serotonin reuptake inhibitors (SSRI) in a sample of patients with obsessive,compulsive disorder (OCD). A total of 55 patients diagnosed as OCD according to revised 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders criteria underwent a 12-week standardized SSRI treatment. According to ,treatment response', defined as at least a 35% drop in the Yale,Brown Obsessive,Compulsive Scale total score, OCD patients were divided into two groups. A total of 32 (58.2%) patients who responded to treatment and 23 (41.8%) who did not, were compared in terms of sociodemographic and clinical characteristics. The authors' findings demonstrated that the severity of obsession,compulsions and disability in work, social and family lives at the beginning of treatment were significantly higher in OCD patients who did not respond to treatment in comparison to those who did. Linear regression analysis, however, revealed that Sheehan Disability Scale-work score at baseline was a predictor of response to SSRI treatment. The higher levels of disability at the beginning of treatment in patients with OCD are associated with a poorer response to SSRI. [source]


Pharmacokinetics and efficacy of a direct switch from conventional depot to risperidone long-acting injection in Chinese patients with schizophrenic and schizoaffective disorders

PSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 4 2009
Ying-Ching Lai md
Aims:, This 12-week open-label study was designed to investigate the pharmacokinetics and efficacy of a direct switch from a conventional depot to long-acting injectable risperidone in patients with schizophrenia and schizoaffective disorder. Methods:, Men or women from 18 to 65 years old with a diagnosis of schizophrenia or schizoaffective disorder were eligible for participation if they had been treated with conventional depot for at least 8 weeks before study entry. Intramuscular long-acting risperidone was administered starting from 25 mg, with the dose flexibly adjusted every two weeks for 12 weeks from week 4. Results:, Of the 25 patients enrolled in this study, 21 completed at least one post-baseline assessment and were thus included in the analysis. The mean serum concentration of risperidone plus 9-hydroxyrisperidone was 29.1 ng/mL at the 12th week after switching, with an average injection dose of 31.25 mg long-acting risperidone every two weeks. The levels of active moiety of risperidone seemed to be higher in Chinese patients compared to those in Caucasian patients. Positive and Negative Syndrome Scale total scores (from 67.5 to 56.4; P = 0.002), scores for negative symptoms (P = 0.006) and general symptoms (P = 0.001) were improved significantly 12 weeks after the switch. Mean Extrapyramidal Symptom Rating Scale scores were improved significantly from 20.1 to 5.5 (P < 0.001). Significantly decreased levels of cholesterol and triglyceride were found at the 12th week. The levels of fasting glucose, low-density lipoprotein, high-density lipoprotein and bodyweight remained unchanged. Conclusions:, These findings suggest that switching from conventional depot to long-acting risperidone is feasible with the advantage of symptom reduction and side-effect profile decrement. [source]


Neurocognitive effects of switching from methylphenidate-IR to OROS-methylphenidate in children with ADHD

HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 2 2009
Yeni Kim
Abstract Objectives This study evaluated neurocognitive changes after switching from immediate release forms of methylphenidate (MPH-IR) to osmotic release oral system methylphenidate (OROS-MPH). Methods 102 children with attention-deficit/hyperactivity disorder (ADHD) participated in an open label, 28,day trial, performing neurocognitive test at baseline and at 28 days after the switch from MPH-IR to OROS-MPH. Results There were significant improvements in the commission error and the reaction time of both visual and auditory continuous performance tests (CPTs) at 28 days after switching from MPH-IR to OROS-MPH. A positive correlation was observed between the improvement in parent/caregiver-rated IOWA Conners total score (, IOWA) and the reduction in commission error (r,=,0.3, p,=,0.001) and reduction in reaction time variability (r,=,0.3, p,=,0.006) of visual CPT. In a linear regression model, the change in parent/caregiver-rated IOWA Conners scale total scores were significant predictors of change in commission error (,,=,0.3, p,=,0.005, CI,=,0.4,2.3, adjusted R2,=,0.12) and RT variability (,,=,0.3, p,=,0.004, CI,=,0.5,2.4, adjusted R2,=,0.09) of visual CPT. Conclusions These data suggest that MPH-IR may be successfully switched to OROS-MPH treatment with associated improvements in neurocognitive performance. Large-scale controlled trials are needed to replicate these findings. Copyright © 2009 John Wiley & Sons, Ltd. [source]