Objective:  To describe the efficacy of inhaled loxapine for the treatment of agitation associated with schizophrenia or bipolar disorder using different examples of effect size (ES). Data sources:  Psychopharmacologic Drug Advisory Committee briefing documents as prepared by the product manufacturer and by the US Food and Drug Administration. Study selection:  ...

Antidepressant drugs are frequently used to treat affective symptoms in schizophrenia. We have recently shown that escitalopram, but not citalopram or R-citalopram, increases firing rate and burst firing of midbrain dopamine neurons, potentiates cortical N-methyl-D-aspartate (NMDA) receptor-mediated transmission and enhances cognition, effects that might influence the outcome of concomitant antipsychotic ...

Tetrahydroprotoberberines (THPBs) are compounds derived from traditional Chinese medicine and increasing preclinical evidence suggests efficacy in treatment of a wide range of symptoms observed in schizophrenia. A receptor-binding profile of the THPB, d.l-govadine (d.l-Gov), reveals high affinity for dopamine and noradrenaline receptors, efficacy as a D2 receptor antagonist, brain penetrance ...

Tardive dyskinesia (TD) is a complex involuntary movement disorder affecting about 23% of neuroleptic-treated patients. Our objective was to retrospectively analyze a combination of tetrabenazine (TBZ), clonazepam (CLONAZ) and clozapine (CLOZ) used simultaneously for TD in psychotic patients. Six patients with severe, unsuccessfully controlled TD were referred for treatment (mean ...

Paliperidone palmitate is a second-generation, long-acting injectable (LAI) antipsychotic recently approved by the US FDA and European Medicines Agency for use in patients with schizophrenia. This article reviews the recommended dosing regimens for initiation and maintenance treatment with paliperidone palmitate in adult patients with schizophrenia. We also address issues of ...

We report a 62-year-old man who have taken major tranquilizer for schizophrenia for the past 24 years. He had sudden generalized tonic-clonic seizure and consciousness loss on April 2010. He was administered diazepam, phenytoin, phenobarbital intravenously and drip-infused with midazolam continuously, but the seizure persisted. For a possible comorbidity of ...

The wakefulness-promoting medication armodafinil (R-modafinil) is being studied as an adjunctive treatment for patients with schizophrenia receiving antipsychotic therapy. This open-label study in 37 adults with schizophrenia evaluated whether a drug-drug interaction occurs between armodafinil (a moderate CYP3A4 inducer) and the atypical antipsychotic quetiapine (primarily metabolized by CYP3A4). Patients were ...

RATIONALE: Accumulating evidence suggests that the primary symptoms of schizophrenia may be associated with altered central glutamate transmission. LY2140023 monohydrate is the methionine prodrug of the selective mGlu(2/3) receptor agonist LY404039 and is currently being assessed for the treatment of schizophrenia. OBJECTIVE: The objective of this study was to evaluate ...

BACKGROUND: Paliperidone extended-release (ER) is approved for treatment of schizophrenia in adults but has not been evaluated in adolescents. METHODS: In this 6-week, double-blind, parallel-group study, participants (n = 201) aged 12 to 17 years, with a Positive and Negative Syndrome Scale (PANSS) total score of 60 to 120 were ...

Paliperidone palmitate (PP) is a recently (USA) approved injectable new-generation antipsychotic. This 53-wk, Phase-III double-blind study was designed to assess the non-inferiority of PP to risperidone long-acting injectable (RIS-LAI) in schizophrenia treatment. Acutely symptomatic patients (n=749), with a Positive and Negative Syndrome Scale (PANSS) total score between 60 and 120 ...

OBJECTIVES: The aim of this study was to assess the short-term tolerability of two titration schedules of sublingual asenapine in older patients with psychosis, not associated with organic brain disease, and to compare asenapine pharmacokinetics in older patients versus younger adults with schizophrenia. METHODS: Patients ≥65 years with psychosis without dementia ...

OBJECTIVES:: The objectives of this 12-week multicenter, open-label, noncomparative study were to evaluate the overall effectiveness of paliperidone extended release (ER), the feasibility of maintaining patients on the initial dose of 6 mg, and the relationship between dose pattern and treatment response in schizophrenic patients with inadequate responses to initial ...

RATIONALE: Prepulse inhibition (PPI) is the reduction in startle response magnitude when intense stimuli are closely preceded by other weak stimuli. Animal models used to investigate sensorimotor gating deficits include both the stimulation of dopamine receptors (e.g., amphetamine or apomorphine) and the blockade of NMDA-glutamate receptors (e.g., dizocilpine or phencyclidine). ...

Meatballs were prepared by mixing ground beef and spices and inoculated with E. coli O157:H7, L. monocytogenes, and S. enteritidis before packaged in modified atmosphere (3% O(2) + 50% CO(2) + 47% N(2) ) or aerobic conditions. The packaged samples were irradiated at 0.75, 1.5, and 3 kGy doses and stored at 4 °C for ...

Quetiapine is often prescribed at higher than approved doses. We investigated the safety, tolerability, and efficacy of quetiapine > 800 mg/d. A trial was carried out from October 2003-September 2005 in 19 referral centers. Patients with DSM-IV schizophrenia or schizoaffective disorder were randomized on the basis of persistent symptoms of ...

To evaluate the prescribing practices in psychiatric residential facilities, with particular focus both on the antipsychotic dose and polypharmacy as well as the variation of antipsychotic patterns during a patient's stay within the facilities. Fifteen residential facilities of Liguria region in Italy were included. Data were collected through a chart ...

Iloperidone is a second-generation antipsychotic drug approved in May 2009 by the US Food and Drug Administration (FDA) for the acute treatment of schizophrenia in adults. It is a piperidinyl-benzisoxazole derivative with mixed serotonin (5HT2A) and D2 dopamine antagonist properties. The purpose of this article was to review the pharmacology, ...

Asenapine tablets are a new option for the treatment of schizophrenia. Sublingual administration is essential because bioavailability if ingested is less than 2%. Efficacy is supported by acute and long-term randomized controlled studies conducted by the manufacturer, with asenapine 5 mg twice daily evidencing superiority over placebo in six-week studies ...

Iloperidone is a new second-generation (atypical) antipsychotic medication approved for the treatment of schizophrenia in adults. The target dose of 6 mg bid can be achieved in 4 days, with titration recommended to minimize postural hypotension. The maximum recommended dose is 12 mg bid. The tolerability profile of iloperidone is ...

Pro-inflammatory and anti-inflammatory mediators derived from arachidonic acid (AA) modulate peripheral inflammation and its resolution. Aspirin (ASA) is a unique non-steroidal anti-inflammatory drug, which switches AA metabolism from prostaglandin E₂ (PGE₂) and thromboxane B₂ (TXB₂) to lipoxin A₄ (LXA₄) and 15-epi-LXA₄. However, it is unknown whether chronic therapeutic doses of ...

we performed the first test in humans of whether aspirin at clinically relevant doses increases nitric oxide (NO) formation. seventy primary prevention patients with metabolic syndrome were randomly assigned to 81 mg, 162.5 mg, 325 mg, 650 mg, or 1300 mg aspirin daily for 12 weeks to test changes in ...

Clopidogrel and aspirin are the most commonly used antiplatelet therapies for percutaneous coronary intervention (PCI). We assessed the effect of various clopidogrel and aspirin regimens in prevention of major cardiovascular events and stent thrombosis in patients undergoing PCI. The CURRENT-OASIS 7 trial was undertaken in 597 centres in 39 countries. ...

There is scarce information about the effects of different doses and enteric-coated preparation of aspirin on platelet function, especially in Asian people, evaluated by the measurement of urinary 11-dehydrothromboxane B2 (dTXB2). The objective of the present study was to assess the effects of different doses, enteric-coated preparation of aspirin, sex ...

The concomitant use of non-steroidal anti-inflammatory drugs is a risk factor for low-dose aspirin (LDA)-associated upper gastrointestinal toxicity. Lafutidine is an H2-receptor antagonist with gastroprotective activity, produced by acting on capsaicin-sensitive afferent neurons. To evaluate the preventive effect of lafutidine on gastric damage caused by LDA alone and by the ...

The objective of this study was to evaluate the antiplatelet effect of clopidogrel 150 mg/day in patients with high on-treatment reactivity (OTR) and to further assess this effect according to CYP2C19 genotype. High OTR is associated with ischemic events in clopidogrel-treated patients after percutaneous coronary intervention. Alternative dosing regimens might ...

Although it is well known that aspirin causes gastroduodenal mucosal injury and that aspirin-induced gastroduodenal mucosal injury is often asymptomatic, the prevalence and independent factors for gastroduodenal mucosal injury have not been clarified in asymptomatic patients taking low-dose aspirin and gastroprotective agents. To clarify the prevalence and independent factors for ...

Previous studies have shown that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) lower colorectal cancer (CRC) risk. However, the lowest effective NSAID dose, treatment duration, and effects on survival are not defined. In a large population-based case-control study, we have explored the relationship between NSAID dose and duration, CRC risk ...

Four randomized, placebo-controlled, crossover studies were conducted among 282 healthy subjects to investigate whether an interaction exists between clopidogrel (300-mg loading dose/75-mg/day maintenance dose) and the proton-pump inhibitor (PPI) omeprazole (80 mg) when they are administered simultaneously (study 1); whether the interaction, if any, can be mitigated by administering clopidogrel ...

The preventive effects of lansoprazole and famotidine on low-dose aspirin-induced gastric mucosal injury in relation to gastric acidity were compared in healthy Japanese volunteers. Fifteen Helicobacter pylori-negative volunteers with different CYP2C19 genotypes were randomly administered aspirin 100 mg, aspirin plus famotidine 20 mg twice daily, or aspirin plus lansoprazole 15 ...

Despite its universal use, the optimal dose of aspirin from an efficacy and safety perspective remains unclear. There are wide variations in international practice and a lack of consensus as to the most appropriate dose of aspirin in patients with acute coronary syndromes (ACS), mainly because of the wide range ...

OBJECTIVES: This study evaluated the platelet inhibitory effects of low-dose enteric-coated aspirin (EC-ASA) when used concomitantly with maximum over-the-counter (OTC) doses of naproxen sodium (NAPSO) or acetaminophen to determine whether NAPSO and acetaminophen interfere with the anti-platelet effect of aspirin. RESEARCH DESIGN AND METHODS: Phase I, randomized, open-label, multi-dose, three-period, ...

Aspirin administration decreases the risk of vascular ischemic problems. However, aspirin withdrawal may temporarily increase this risk. Previous studies reported that high dilutions of aspirin might cause a pro-thrombotic effect. This paper studies the effect of the lower end of the aspirin dose-response curve, its possible mechanism and clinical implications. ...

BACKGROUND: Thrombotic stroke following carotid endarterectomy (CEA) is preceded by high-grade embolisation (detected using transcranial Doppler (TCD)) and can be prevented by incremental doses of Dextran. However, this strategy is labour intensive and Dextran manufacture has now ceased. A randomised trial has suggested that a single 75 mg dose of ...

OBJECTIVE: To evaluate the efficacy of aspirin for the treatment and prevention of ischemic stroke and identify the minimum dose proven to be effective for each indication. DATA SOURCES: PubMed and MEDLINE searches (up to January 2010) were performed to identify primary literature, using search terms including aspirin, stroke prevention, ...

This open-label prospective study compared the antiplatelet potency of sarpogrelate, aspirin, and beraprost in 20 healthy volunteers according to in-vitro closure time. Volunteers were assigned to receive sarpogrelate, aspirin, or beraprost for 14 days, then given 14 days of washout, then switched to another of these medications. We measured in-vitro ...

BACKGROUND: Inflammation is a key factor in the development of atherosclerotic disease and acute coronary syndromes (ACS). The P2Y(12) receptor antagonists ticagrelor (AZD6140) and clopidogrel may have anti-inflammatory effects. The objective of this analysis from the Dose Confirmation Study Assessing Anti-Platelet Effects of AZD6140 vs Clopidogrel in NSTEMI 2 (DISPERSE ...

Niacin is the most effective lipid-modifying agent for raising high-density lipoprotein cholesterol levels, but it also causes cutaneous vasodilation with flushing. To determine the frequency of flushing in clinical trials, as well as to delineate counseling and treatment approaches to prevent or manage flushing, a MEDLINE search was conducted of ...

Aspirin has been extensively used in clinical settings. Its side effects on auditory function, including hearing loss and tinnitus, are considered as temporary. A recent promising finding is that chronic treatment with high-dose salicylate (the active ingredient of aspirin) for several weeks enhances expression of the outer hair cell (OHC) ...

OBJECTIVE: Low-dose enteric-coated aspirin is increasingly being used for prevention of cardiovascular disease. The aim of this study was to evaluate whether geranylgeranylacetone (GGA) could prevent aspirin-induced small bowel injury. MATERIAL AND METHODS: This was a prospective, randomized, double-blind, pilot study of GGA versus placebo in subjects taking low-dose enteric-coated ...

Cyclooxygenase (COX)-2 inhibition has been reported to suppress the biosynthesis of the gastroprotective lipoxygenase metabolite 15(R)-epi-lipoxin A(4), also termed 'aspirin-triggered lipoxin' (ATL). We tested the hypothesis that the co-administration of aspirin with either the selective COX-2 inhibitor celecoxib or the nonselective COX inhibitor ibuprofen reduces ATL biosynthesis. We measured the ...

PURPOSE: We optimized agent testing in an in vivo bladder cancer model and determined the most sensitive, relevant protocol to test efficacy in clinical prevention trials. MATERIALS AND METHODS: Female Fischer-344 rats (Harlan) were treated with the bladder carcinogen OH-BBN (TCI America, Portland, Oregon) for 8 weeks. Rats were treated ...

Platelets and coagulation system play a pivotal part in the progression of peripheral arterial disease (PAD) and the genesis of complications. Therefore, antiplatelet and antithrombotic drugs represent one of the basic options for prevention and the treatment in such patients. As the data on the efficacy of these drugs in ...

Kawasaki disease (KD) is an acute systemic inflammatory illness of young children that can result in coronary artery aneurysms, myocardial infarction and sudden death in previously healthy children. Clinical and epidemiologic features support an infectious cause, but the etiology remains unknown four decades after KD was first identified by Tomisaku ...

BACKGROUND: Variation in and irreversibility of platelet inhibition with clopidogrel has led to controversy about its optimum dose and timing of administration in patients with acute coronary syndromes. We compared ticagrelor, a more potent reversible P2Y12 inhibitor with clopidogrel in such patients. METHODS: At randomisation, an invasive strategy was planned ...

The role of aspirin for the primary prevention of stroke in patients with non valvular atrial fibrillation is critically reviewed. It is shown that the currently held belief that aspirin (at doses of 75 to 325 mg daily) is an effective treatment is based on a flawed interpretation of the ...

BACKGROUND: Gastroduodenal ulcers are common in patients taking low-dose aspirin. However, the factors predisposing to mucosal erosions, the precursor lesions, are not well known. AIMS: To examine the potential risk factors for the development of erosions in patients chronically taking low-dose aspirin. METHODS: Patients included were taking aspirin 75-325 mg ...

Clopidogrel is used with aspirin as a standard combined treatment in patients with acute coronary syndrome. A proton pump inhibitor (PPI) is often administered to patients receiving antiplatelet therapy. However, PPI use with clopidogrel was recently shown to result in increased risk of major cardiovascular events when compared to clopidogrel ...

Peptic ulcer bleeding (PUB) is a serious and sometimes fatal condition. The outcome of PUB strongly depends on the risk of rebleeding. A recent multinational placebo-controlled clinical trial (ClinicalTrials.gov identifier: NCT00251979) showed that high-dose intravenous (IV) esomeprazole, when administered after successful endoscopic haemostasis in patients with PUB, is effective in ...

In the United States and Europe, patients with coronary stents are maintained on 75 mg clopidogrel. Because the maintenance dose of ticlopidine in patients with coronary stents is 100 mg twice daily in Japan and 250 mg twice daily in the United States and Europe, in Japanese patients a lower ...

Low dose aspirin (</=325 mg) is routinely used for primary and secondary prophylaxis of cardiovascular and cerebrovascular events. The use of low dose aspirin is associated with two- to four-fold greater risk of symptomatic or complicated peptic ulcers. Risk factors associated with low dose aspirin induced gastrointestinal toxicity includes prior ...