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Tolerability
Kinds of Tolerability Terms modified by Tolerability Selected AbstractsIbudilast in healthy volunteers: safety, tolerability and pharmacokinetics with single and multiple dosesBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2008Paul Rolan WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Ibudilast is an oral drug approved in Asia for asthma. , Tolerability of 10-mg regimens has been described previously. , Published pharmacokinetics (PK) are limited: single or 7-day repeat oral administration of 10 mg in healthy male Asian volunteers. WHAT THIS STUDY ADDS , Safety/tolerability and PK of a single 30-mg dose and a 30-mg twice daily (b.i.d.) 2-week regimen in male and female healthy volunteers. , Higher-dose regimens are relevant for testing in new neurological indications. , LC-MS/MS analytics for quantification of plasma and urine levels of ibudilast parent and its primary metabolite (6,7-dihydrodiol-ibudilast). AIMS To investigate the safety, tolerability and pharmacokinetics (PK) of ibudilast after a single-dose and a multiple-dose regimen. METHODS Healthy adult male (n = 9) and female (n = 9) volunteers were evaluated over a 17-day stay in a Phase 1 unit. Subjects were randomized 1 : 3 to either oral placebo or ibudilast at 30-mg single administration followed by 14 days of 30 mg b.i.d. Complete safety analyses were performed and, for PK, plasma and urine samples were analysed for ibudilast and its major metabolite. RESULTS Ibudilast was generally well tolerated. No serious adverse events occurred. Treatment-related adverse events included hyperhidrosis, headache and nausea. Two subjects discontinued after a few days at 30 mg b.i.d. because of vomiting. Although samples sizes were too small to rule out a sex difference, PK were similar in men and women. The mean half-life for ibudilast was 19 h and median Tmax was 4,6 h. Mean (SD) steady-state plasma Cmax and AUC0,24 were 60 (25) ng ml,1 and 1004 (303) ng h ml,1, respectively. Plasma levels of 6,7- dihydrodiol-ibudilast were approximately 30% of the parent. CONCLUSIONS Ibudilast is generally well tolerated in healthy adults when given as a single oral dose of 30 mg followed by 30 mg b.i.d. (60 mg day,1) for 14 days. Plasma PK reached steady state within 2 days of starting the b.i.d. regimen. Exposure to ibudilast was achieved of a magnitude comparable to that associated with efficacy in rat chronic pain models. [source] A RETROSPECTIVE CHART REVIEW OF THE TOLERABILITY AND EFFICACY OF INTRAVENOUS IMMUNOGLOBULIN IN THE TREATMENT OF ALZHEIMER'S DISEASEJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 4 2008Gayatri Devi MD No abstract is available for this article. [source] Tolerability, Safety, and Efficacy of ,-Blockade in Black Patients With Heart Failure in the Community Setting: Insights From a Large Prospective ,-Blocker RegistryCONGESTIVE HEART FAILURE, Issue 1 2007William T. Abraham MD Heart failure (HF) clinical trials suggest different responses of blacks and whites to ,-blockers. Differences between clinical trial and community settings may also have an impact. The Carvedilol Heart Failure Registry (COHERE) observed experience with carvedilol in 4280 patients with HF in a community setting. This analysis compares characteristics, outcomes, and carvedilol dosing of blacks and whites in COHERE. Compared with whites (n=3433), blacks (n=523) had more severe HF symptoms despite similar systolic function. At similar carvedilol maintenance doses, symptoms improved in 33% of blacks vs 28% of whites, while worsening in 10% and 11%, respectively (both nonsignificant), and HF hospitalization rates were reduced comparably in both groups (,58% vs ,56%, respectively; both P<.001). Incidence and hazard ratios of death were similar in blacks and whites (6.9% vs 7.5%, hazard ratio 1.2 vs 1.0, P=.276). Thus carvedilol was similarly effective in blacks and whites with HF in the community setting, consistent with carvedilol clinical trials. [source] A review of studies describing the use of acetyl cholinesterase inhibitors in Parkinson's disease dementiaACTA PSYCHIATRICA SCANDINAVICA, Issue 6 2005I. D. Maidment Objective:, To review the literature relating to the use of acetyl cholinesterase inhibitors in Parkinson's disease dementia (PDD). Method:, MEDLINE (1966 , December 2004), PsychINFO (1972 , December 2004), EMBASE (1980 , December 2004), CINHAL (1982 , December 2004), and the Cochrane Collaboration were searched in December 2004. Results:, Three controlled trials and seven open studies were identified. Efficacy was assessed in three key domains: cognitive, neuropsychiatric and parkinsonian symptoms. Conclusion:, Cholinesterase inhibitors have a moderate effect against cognitive symptoms. There is no clear evidence of a noticeable clinical effect against neuropsychiatric symptoms. Tolerability including exacerbation of motor symptoms , in particular tremor , may limit the utility of cholinesterase inhibitors. [source] Critical review of oral drug treatments for diabetic neuropathic pain,clinical outcomes based on efficacy and safety data from placebo-controlled and direct comparative studiesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 3 2005Hugo Adriaensen Abstract The present review aims to evaluate the efficacy and safety of a selection of oral treatments for the management of painful diabetic neuropathy. A literature review was conducted retrieving placebo-controlled and direct comparative studies with a selection of oral treatments for painful diabetic neuropathy. All studies were analyzed with regard to efficacy and tolerability. Efficacy was evaluated as the percentage improvement in pain intensity between baseline and endpoint. Tolerability was evaluated by means of study discontinuations due to adverse events and by incidence of drug-related adverse events. The analyzed trials enrolled different patient populations with mostly small numbers of patients. The great variability in dosages and dose titration schemes, cross-over designs with variable wash-out periods, and other design schemes made comparison between the different studies difficult. Gabapentin, lamotrigine, tramadol, oxycodone, mexiletine, and acetyl-L-carnitine were the only treatments studied in large (at least 100 patients), placebo-controlled parallel group trials. It is concluded that standardization in design and reporting for comparison of treatments is needed. Validated questionnaires for evaluation of the efficacy and safety should be further developed. Based on the reviewed randomised controlled trials, gabapentin shows good efficacy, a favourable side-effect profile with lack of drug interactions and therefore it may be a first choice treatment in painful diabetic neuropathy, especially in the elderly. However, head to head trials of current treatments are lacking and therefore randomized controlled trials are required to address this issue. Copyright © 2005 John Wiley & Sons, Ltd. [source] A randomized trial of classical and medium-chain triglyceride ketogenic diets in the treatment of childhood epilepsyEPILEPSIA, Issue 5 2009Elizabeth G. Neal Summary Purpose:, To conduct the first randomized trial on classical and medium-chain triglyceride (MCT) versions of the ketogenic diet, examining efficacy and tolerability after 3, 6, and 12 months. Methods:, One hundred forty-five children with intractable epilepsy were randomized to receive a classical or an MCT diet. Seizure frequency was assessed after 3, 6, and 12 months. Treatment withdrawals were documented. Tolerability was assessed by questionnaire, and blood ketone levels were measured. Results:, Of the 61 children who started a classical diet and the 64 who started an MCT diet, data from 94 were available for analysis: 45 classical and 49 MCT. After 3, 6, and 12 months there were no statistically significant differences in mean percentage of baseline seizures between the two groups (3 months: classical 66.5%, MCT 68.9%; 6 months: classical 48.5%, MCT 67.6%; 12 months: classical 40.8%, MCT 53.2%; all p > 0.05). There were no significant differences between groups in numbers achieving greater than 50% or 90% seizure reduction. Serum acetoacetate and ,-hydroxybutyrate levels at 3 and 6 months were significantly higher in children on the classical diet (p < 0.01); this was the case at 12 months for acetoacetate. There were no significant differences in tolerability except increased reports in the classical group of lack of energy after 3 months and vomiting after 12 months. Discussion:, This study has shown classical and MCT ketogenic diet protocols to be comparable in efficacy and tolerability; both ways of implementing the diet have their place in the treatment of childhood epilepsy. [source] Efficacy and Tolerability of the Ketogenic Diet According to Lipid:Nonlipid Ratios,Comparison of 3:1 with 4:1 DietEPILEPSIA, Issue 4 2007Joo Hee Seo Summary:,Purpose: The ketogenic diet (KD) has been considered a highly potent antiepileptic treatment for intractable childhood epilepsy. In this study, we compared the antiepileptic efficacy and diet tolerability of two different diets with lipid:nonlipid ratios of 3:1 and 4:1. Methods: Seventy-six patients with refractory childhood epilepsy were randomly placed into two groups and were started on KD diets with nonlipid:lipid ratios of either 3:1 or 4:1. Antiepileptic efficacy and diet tolerability were evaluated 3 months after initiating the diet. Patients showing seizure-free outcome with the 4:1 diet were changed to the 3:1 diet, and those without a seizure-free outcome on the 3:1 diet were changed to the 4:1 diet, for three more months, after which time their progress was monitored. Results: (1) Antiepileptic efficacy was higher for the 4:1 than the 3:1 diet (p < 0.05). Twenty-two (55.0%) of 40 patients on the 4:1 diet and 11 (30.5%) of 36 patients on the 3:1 diet became seizure free. Seizure reduction of over 90% was observed in 2 (5.0%) patients on the 4:1 diet, and 2 (5.6%) on the 3:1 diet. (2) Dietary tolerability was better for the 3:1 than the 4:1 diet. Gastrointestinal symptoms were observed in 5 (13.9%) patients with the 3:1 diet and 14 (35.0%) patients with the 4:1 diet (p < 0.05). (3) For seizure-free patients who started on the 4:1 diet, antiepileptic efficacy was maintained after changing to the 3:1 diet, while 10 (83.3%) of 12 patients who were not seizure free with the 3:1 diet showed increased seizure reduction after changing to the 4:1 diet. (4) Complications from the KD and laboratory data were not significantly different between the two groups. Conclusions: The 4:1 KD showed greater antiepileptic efficacy than the 3:1 diet with higher seizure-free outcome. In most cases, seizure free outcome was maintained even after changing the ratio to 3:1. Dietary tolerability was better in the 3:1 diet than the 4:1 with less frequent gastrointestinal symptoms. [source] Response: Efficacy and Tolerability of the New Antiepileptic DrugsEPILEPSIA, Issue 12 2004Jacqueline A. French No abstract is available for this article. [source] Efficacy and Tolerability of the New Antiepileptic Drugs, II: Treatment of Refractory Epilepsy.EPILEPSIA, Issue 11 2004QSS Subcommittees of the American Academy of Neurology, Report of the TTA, the American Epilepsy Society No abstract is available for this article. [source] Efficacy and Tolerability of the New Antiepileptic Drugs, I: Treatment of New-Onset Epilepsy: Report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy SocietyEPILEPSIA, Issue 5 2004Jacqueline A. French Summary: Purpose: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs [AEDs; gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS), reviewed in the order in which these agents received approval by the U.S. Food and Drug Administration] in the treatment of children and adults with newly diagnosed partial and generalized epilepsies. Methods: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane Library for relevant articles from 1987 until September 2002, with selected manual searches up to 2003. Results: Evidence exists, either from comparative or dose-controlled trials, that GBP, LTG, TPM, and OXC have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. Evidence also shows that LTG is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking. Conclusions: The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes for which more evidence is necessary. [source] A longitudinal observational study of a cohort of patients with relapsing,remitting multiple sclerosis treated with glatiramer acetateEUROPEAN JOURNAL OF NEUROLOGY, Issue 11 2007M. Debouverie Immunomodulatory treatments for relapsing,remitting multiple sclerosis (RRMS) are not efficacious or tolerated in all patients. It is important to evaluate alternative classes of treatment in patients failing first-line therapy. The objective of this prospective observational study was to evaluate the efficacy and safety of glatiramer acetate in patients, to whom , -interferons could not be administered. The study included patients with RRMS who were intolerant to or had contraindications to , -interferon. After initiation of glatiramer acetate treatment, follow-up visits were made every 3 months, when data on neurologist-ascertained relapses and disability [Expanded Disability Status Scale (EDSS) score] were collected. Tolerability was evaluated by spontaneous adverse event reporting. Overall, 205 patients were studied and 113 (55.1%) treated for at least 4 years. The proportion of patients presenting over three relapses per year decreased from 51.2% to 8.4% in the 2 years following treatment initiation. Over 5 years of treatment, mean annualized relapse rates and mean EDSS scores remained stable (0.4,0.6 relapses/year and 3.6 ± 1.8,3.3 ± 2.1 respectively). Adverse events were reported by 179 patients, leading to discontinuation of treatment in 10 patients. Patients with RRMS to whom , -interferons cannot be prescribed can benefit from treatment with glatiramer acetate. [source] Sumatriptan Nasal Spray in Adolescent Migraineurs: A Randomized, Double-Blind, Placebo-Controlled, Acute StudyHEADACHE, Issue 2 2006Paul Winner DO Objective.,To compare the efficacy and tolerability of sumatriptan nasal spray (NS) (5, 20 mg) versus placebo in the acute treatment of migraine in adolescent subjects. Background.,Currently, no triptan is approved in the United States for the treatment of migraine in adolescent subjects (12 to 17 years). In a previous randomized, placebo-controlled study of 510 adolescent subjects, sumatriptan NS at 5, 10, and 20 mg doses was well tolerated. However, the primary efficacy analysis for headache relief with 20 mg at 2 hours did not demonstrate statistical significance (P= .059). A second study was initiated to evaluate the efficacy of sumatriptan NS in this population. Methods.,This was a randomized (1:1:1), placebo-controlled, double-blind, parallel-group study. Overall, 738 adolescent subjects (mean age: 14 years) with ,6-month history of migraine (with or without aura) self-treated a single attack of moderate or severe migraine. The primary endpoints were headache relief at 1 hour and sustained relief from 1 to 24 hours. Pain-free rates, presence/absence of associated symptoms, headache recurrence, and use of rescue medications were also assessed. Tolerability was based on adverse events (AEs) and vital signs. Results.,Sumatriptan NS 20 mg provided greater headache relief than placebo at 30 minutes (42% vs. 33%, respectively; P= .046) and 2 hours (68% vs. 58%; P= .025) postdose, but did not reach statistical significance at 1 hour (61% vs. 52%; P= .087) or for sustained headache relief from 1 to 24 hours (P= .061). Significant differences (P < .05) in favor of sumatriptan NS 20 mg over placebo were observed for several secondary efficacy endpoints including sustained relief from 2 to 24 hours. In general, sumatriptan NS 5 mg percentages were slightly higher than placebo but the differences did not reach statistical significance. Both doses of sumatriptan NS were well tolerated. No AEs were serious or led to study withdrawal. The most common event was taste disturbance (2%, placebo; 19%, sumatriptan NS 5 mg; 25%, sumatriptan NS 20 mg). Conclusions.,This study suggests that sumatriptan may be beneficial to some adolescents and is generally well tolerated in the acute treatment of migraine in this population. [source] Long-Term Tolerability of Sumatriptan Nasal Spray in Adolescent Patients With MigraineHEADACHE, Issue 10 2004Shankar Natarajan MD Objective.,This 1-year, open-label, multicenter study was designed to assess the long-term tolerability and efficacy of sumatriptan nasal spray 20 mg in adolescent patients with migraine. Methods.,A prospective, multicenter, open-label study was conducted in patients aged 12 to 17 years who were allowed to treat an unlimited number of migraines at severe, moderate, or mild pain intensity with sumatriptan nasal spray for up to 1 year. All patients started the study at the 20-mg dose of sumatriptan nasal spray. Dose could be adjusted downward to 5 mg at the discretion of the investigator to optimize therapy. Results.,A total of 484 adolescent migraineurs treated 4676 migraines with sumatriptan nasal spray 20 mg (3593 during the first 6 months and 1083 during the second 6 months). A total of 3940 migraines and 699 migraines were treated with one and two 20-mg doses of sumatriptan nasal spray, respectively. Only 10 patients (treating 42 migraines) took the 5-mg dose of sumatriptan nasal spray. The overall percentage of migraines treated with either one 20-mg dose or one, two, or three 20-mg doses with at least 1 drug-related adverse event was 19%. The most common specific drug-related adverse event was unpleasant taste, reported in 17% of migraines. No other single drug-related adverse event was reported in more than 1% of migraines over the 1-year treatment period. When unpleasant taste was excluded from the adverse-event tabulations, the percentages of migraines with at least 1 drug-related adverse event after one or one, two, or three 20-mg doses declined to 4% and 3%, respectively. No patient experienced any drug-related changes in 12-lead ECGs, vital signs, or nasal assessments; and no clinically meaningful changes in clinical laboratory values were observed. Across all migraines with evaluable efficacy data (n = 4334), headache relief was reported in 43% of migraines at 1 hour and in 59% at 2 hours after dosing with sumatriptan nasal spray 20 mg. Of the 2561 migraines with headache relief 2 hours postdose, headache recurrence was reported within 24 hours of initial dosing in 7% of migraines. None of the efficacy or tolerability results varied as a function of time in the study (ie, first 6 months vs. second 6 months). Conclusion.,Sumatriptan nasal spray 20 mg is generally well tolerated and may be beneficial during long-term use by adolescent migraineurs ages 12 to 17 years. [source] Cardiovascular Tolerability and Safety of Triptans: A Review of Clinical DataHEADACHE, Issue 2004David W. Dodick MD Triptans are not widely used in clinical practice despite their well-established efficacy, endorsement by the US Headache Consortium, and the demonstrable need to employ effective intervention to reduce migraine-associated disability. Although the relatively restricted use of triptans may be attributed to several factors, research suggests that prescribers' concerns about cardiovascular safety prominently figure in limiting their use. This article reviews clinical data,including results of clinical trials, postmarketing studies and surveillance, and pharmacodynamic studies,relevant to assessing the cardiovascular safety profile of the triptans. These data demonstrate that triptans are generally well tolerated. Chest symptoms occurring during use of triptans are usually nonserious and usually not attributed to ischemia. Incidence of triptan-associated serious cardiovascular adverse events in both clinical trials and clinical practice appears to be extremely low. When they do occur, serious cardiovascular events have most often been reported in patients at significant cardiovascular risk or in those with overt cardiovascular disease. Adverse cardiovascular events also have occurred, however, in patients without evidence of cardiovascular disease. Several lines of evidence suggest that nonischemic mechanisms are responsible for sumatriptan-associated chest symptoms, although the mechanism of chest symptoms has not been determined to date. Importantly, most of the clinical trials and clinical practice data on triptans are derived from patients without known cardiovascular disease. Therefore, the conclusions of this review cannot be extended to patients with cardiovascular disease. The cardiovascular safety profile of triptans favors their use in the absence of contraindications. [source] Topiramate as an Adjunctive Treatment in Migraine ProphylaxisHEADACHE, Issue 10 2003Héctor R. Martínez MD Background.,Anticonvulsants now are commonly used for headache prevention. Topiramate, one of the newer anticonvulsants, recently has been demonstrated to be effective as monotherapy for migraine prophylaxis. Objective.,To assess the efficacy, safety, and tolerability of topiramate as adjunctive prophylactic therapy for migraine. Material and Methods.,A prospective trial involving patients with more than 3 migraine attacks per month was performed. Patients continued their usual prophylactic treatment. Baseline analgesic use and frequency and duration of migraine attacks were recorded. A 4-point visual analog scale evaluated severity. Laboratory tests, electrocardiogram, and computed tomography or magnetic resonance imaging were performed before study entry. After informed consent was obtained, patients were instructed to take 25 mg of topiramate per day, with 25- to 50-mg weekly increments to a maximum of 100 mg per day. Safety was assessed at the first month; tolerability and efficacy were assessed every week for the first month and then every month for 3 months. Effectiveness was assessed by comparing baseline and on-treatment migraine status, and data were analyzed by the Fisher exact test. Results.,Twenty-five women and 11 men (mean age, 44 years) were evaluated. Existing prophylactic treatment was either propranolol or flunarizine (or both) in 80% of the patients. At 3 months of therapy with topiramate, headache frequency decreased from 17 to 3 episodes per month, headache duration from 559 to 32 minutes, and intensity from 9 to 1 by visual analog scale (P < .001). Improvement in frequency and severity of migraine was observed in 83% of patients. Slight or no changes in headache were observed in 6 patients. Tolerability was good in 30 patients. The most common side effects were acroparesthesias, weight loss, sleepiness, and headache worsening. No adverse interaction with propranolol or flunarizine was observed. Conclusions.,These results suggest that topiramate is efficacious and safe as an adjunctive treatment in patients with migraine whose prior response to prophylactic management has been less than satisfactory. [source] Tolerability and Safety of Frovatriptan With Short- and Long-term Use for Treatment of Migraine and in Comparison With SumatriptanHEADACHE, Issue 2002Gilles Géraud MD Objective.,To evaluate the tolerability and safety of frovatriptan 2.5 mg in patients with migraine. Background.,Frovatriptan is a new, selective serotonin agonist (triptan) developed for the acute treatment of migraine. Dose range-finding studies identified 2.5 mg as the dose that conferred the optimal combination of efficacy and tolerability. Methods.,The tolerability and safety of frovatriptan 2.5 mg were assessed during controlled, acute migraine treatment studies, including a study that compared frovatriptan 2.5 mg with sumatriptan 100 mg, as well as a 12-month open-label study during which patients could take up to three doses of frovatriptan 2.5 mg within a 24-hour period. Safety and tolerability were assessed through the collection of adverse events, monitoring of heart rate and blood pressure performance of 12-lead electrocardiogram, hematology screen, and blood chemistry studies. Results.,In the short-term studies, 1554 patients took frovatriptan 2.5 mg and 838 took placebo. In the 12-month study, 496 patients treated 13 878 migraine attacks. Frovatriptan was well tolerated in the short- and long-term studies with 1% of patients in the short-term studies and 5% of patients in the long-term study withdrawing due to lack of tolerability. The incidence of adverse events was higher in the frovatriptan-treated patients than in the patients who took placebo (47% versus 34%) and the spectrum of adverse events was similar. When compared to sumatriptan 100 mg, significantly fewer patients taking frovatriptan experienced adverse events (43% versus 36%; P=.03) and the number of adverse events was lower (0.62 versus 0.91), there were also fewer adverse events suggestive of cardiovascular symptoms in the frovatriptan group. Analysis of the entire clinical database (n=2392) demonstrated that frovatriptan was well tolerated by the patients regardless of their age, gender, race, concomitant medication, or the presence of cardiovascular risk factors. No effects of frovatriptan on heart rate, blood pressure, 12-lead electrocardiogram, hematology screen, or blood chemistry were observed. No patient suffered any treatment-related serious adverse event. Conclusions.,Short- and long-term use of frovatriptan 2.5 mg was well tolerated by a wide variety of patients. Frovatriptan treatment produced an adverse events profile similar to that of placebo, and in a direct comparison study was better tolerated than sumatriptan 100 mg. [source] Long-term safety and efficacy of long-acting risperidone in elderly psychotic patientsHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2007Werner Kissling Abstract This subgroup analysis of the 6-month, open-label Switch to Risperidone Microspheres (StoRMi) trial evaluated long-term safety and efficacy of a direct conversion to risperidone long-acting injectable (RLAI) in 52 elderly patients (,65 years) with psychosis stabilized on oral or depot antipsychotic. Study outcomes included adverse events, movement disorder severity, psychiatric symptoms, functional ability, quality of life and patient satisfaction. Change in the Positive and Negative Syndrome Scale at endpoint was the primary efficacy measure. The most common dosage of RLAI used at endpoint was 25,mg every 14 days (60%). The trial was completed by 81% of patients, with six patients discontinuing treatment due to an adverse event. Tolerability was good and most side effects were mild to moderate. Serious adverse events occurred in 11 patients. Two of these (suicidal attempt, n,=,1; exacerbation of disease, n,=,1) were considered possibly related to RLAI. Conversion to RLAI resulted in significant improvements in movement disorder severity, psychiatric symptoms, functional status and patient satisfaction. Mean PANSS total decreased by 15.8 at endpoint, with 23 patients (46.9%) experiencing a ,20% improvement. This post-hoc analysis supports that RLAI is well tolerated and safe in elderly patients with psychotic illnesses switched from stable antipsychotic regimens, and suggests possible efficacy, although inferences are limited. Copyright © 2007 John Wiley & Sons, Ltd. [source] Tianeptine and paroxetine in major depressive disorder, with a special focus on the anxious component in depression: an international, 6-week double-blind study,HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 3 2001Jean Pierre Lepine Abstract Tianeptine (37.5,mg/day) and paroxetine (20,mg/day) were compared in a population of depressive patients without past or current history of co-morbid anxiety and/or important anxiolytic treatment. In a 6-week, double blind trial, the special focus was on anxious symptoms. Both drugs showed good efficacy on depressive symptomatology, assessed with MADRS and HDRS, but no difference was detected between tianeptine and paroxetine, for any assessment criterion. Despite the choice of selected depressive patients, without any co-morbid anxious disorder, anxiety scale scores at inclusion (HAMA and BAS) were appreciable but correlated poorly with depressive scores. Both tianeptine and paroxetine improved the apparent anxious component in depression. Tolerability of both drugs was good, although significantly better with tianeptine. Thus tianeptine and paroxetine are effective and safe treatments for major depression and may also act directly on the anxious component of the psychopathology. Copyright © 2001 John Wiley & Sons, Ltd. [source] Duloxetine 60 mg once daily in the treatment of milder major depressive disorderINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 5 2006D. G. S. Perahia Summary There is ongoing debate regarding the effectiveness of antidepressants in patients with milder major depressive disorder (MDD). This post-hoc analysis evaluated the efficacy and tolerability of duloxetine in the subset of 159 (75 duloxetine and 84 placebo) patients with milder MDD (baseline HAMD17 total score ,15 and ,18) who were treated once daily with duloxetine 60 mg or placebo in two identical, 9-week, randomised, double-blind trials. At endpoint, change from baseline on HAMD17 was greater in the duloxetine group (,7.0) than in the placebo group (,4.1) (p = 0.005). Response and remission rates, and improvement on the Clinical Global Impressions-Severity (CGI-S) scale, the Patient Global Impressions-Improvement (PGI-I) scale, and measures of painful symptoms were also significantly better in the duloxetine group (p < 0.05). Tolerability was consistent with that seen in previous studies of duloxetine in patients with more severe depression. In conclusion, duloxetine 60 mg/day is effective and well tolerated in milder MDD. [source] Tolerability and safety of fluvoxamine and other antidepressantsINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 4 2006H. G. M. Westenberg Summary Selective serotonin [5-hydroxytryptamine (5-HT)] reuptake inhibitors (SSRIs) and the 5-HT noradrenaline reuptake inhibitor, venlafaxine, are mainstays in treatment for depression. The highly specific actions of SSRIs of enhancing serotonergic neurotransmission appears to explain their benefit, while lack of direct actions on other neurotransmitter systems is responsible for their superior safety profile compared with tricyclic antidepressants. Although SSRIs (and venlafaxine) have similar adverse effects, certain differences are emerging. Fluvoxamine may have fewer effects on sexual dysfunction and sleep pattern. SSRIs have a cardiovascular safety profile superior to that of tricyclic antidepressants for patients with cardiovascular disease; fluvoxamine is safe in patients with cardiovascular disease and in the elderly. A discontinuation syndrome may develop upon abrupt SSRI cessation. SSRIs are more tolerable than tricyclic antidepressants in overdose, and there is no conclusive evidence to suggest that they are associated with an increased risk of suicide. Although the literature suggests that there are no clinically significant differences in efficacy amongst SSRIs, treatment decisions need to be based on considerations such as patient acceptability, response history and toxicity. [source] Tolerability of switching from donepezil to memantine treatment in patients with moderate to severe Alzheimer's diseaseINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 9 2008Gunhild Waldemar No abstract is available for this article. [source] Randomized, Placebo-Controlled Trial of the Cognitive Effect, Safety, and Tolerability of Oral Extended-Release Oxybutynin in Cognitively Impaired Nursing Home Residents with Urge Urinary IncontinenceJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 5 2008Thomas E. Lackner PharmD OBJECTIVES: Determine the cognitive effect, safety, and tolerability of oral extended-release oxybutynin in cognitively impaired older nursing home residents with urge urinary incontinence. DESIGN: Randomized, double-blinded, placebo-controlled trial. SETTING: Twelve skilled nursing homes. PARTICIPANTS: Fifty women aged 65 and older with urge incontinence and cognitive impairment. INTERVENTION: Four-week treatment with once-daily oral extended-release oxybutynin 5 mg or placebo. MEASUREMENTS: Withdrawal rates and delirium or change in cognition from baseline at 1, 3, 7, 14, 21, and 28 days after starting treatment using the Confusion Assessment Method (CAM), Mini-Mental State Examination (MMSE), and Severe Impairment Battery (SIB). The Brief Agitation Rating Scale, adverse events, falls incidence, and serum anticholinergic activity change with treatment were also assessed. RESULTS: Participants' mean age ±standard deviation was 88.6±6.2, and MMSE baseline score was 14.5±4.3. Ninety-six percent of subjects receiving oxybutynin (n=26) and 92% receiving placebo (n=24) completed treatment (P=.50). The differences in mean change in CAM score from baseline to all time points were equivalent between the oxybutynin and placebo groups. Delirium did not occur in either group. One participant receiving oxybutynin was withdrawn because of urinary retention, which resolved without treatment. Mild adverse events occurred in 38.5% of participants receiving oxybutynin and 37.5% receiving placebo (P=.94). CONCLUSION: Short-term treatment using oral extended-release oxybutynin 5 mg once daily was safe and well tolerated, with no delirium, in older female nursing home participants with mild to severe dementia. Future research should investigate different dosages and long-term treatment. [source] Tolerability and improved protective action of idebenone-loaded pegylated liposomes on ethanol-induced injury in primary cortical astrocytes,JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2004Donatella Paolino Abstract The potential therapeutic advantages of the encapsulation of idebenone within pegylated liposomes were investigated in vitro on primary cortical astrocytes of rats. In particular, both the concentration-dependent effects and the therapeutic effectiveness toward excitotoxic injury, elicited by chronic treatment with ethanol (100 ,M) for 12 days, were evaluated. The following parameters were taken into consideration to assay free or liposomally entrapped idebenone: lactic dehydrogenase release, respiratory capacity measured by tetrazolium salt conversion, glutamine synthetase, and the levels of constitutive and inducible 70-kDa heat shock proteins. To evaluate the effects on astrocytes, three different drug concentrations were used (0.5 ,M, 5 ,M, and 50 ,M). At the highest concentration used (50 ,M), a toxic effect of the free and liposomally entrapped drug was observed. Toxic effects seem to be due to a cellular membrane perturbation, as demonstrated by 45Ca2+ permeation. The therapeutic effect of free or liposomally entrapped idebenone on ethanol-induced injury of primary cortical astrocytes was evaluated as a function of the drug concentration. The drug liposome formulation was much more effective than the free drug in counteracting the ethanol-induced damage in astrocytes, i.e., 10-times-lower doses of liposomally entrapped idebenone are able to provide a greater protective action than the free drug. The improved action of idebenone-loaded liposomes is probably due to the greater drug bioavailability at the cellular level. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1815,1827, 2004 [source] Clinical comparison of two self-directed bleaching systemsJOURNAL OF PROSTHODONTICS, Issue 4 2003Katherine Karpinia DMD Purpose This randomized clinical trial compared the clinical efficacy and tolerability of 2 marketed self-directed vital tooth-whitening systems. Materials and Methods Balancing for baseline tooth color, self-reported coffee/tea use, and age, 57 adult volunteers were randomized to either a whitening strip containing 6% hydrogen peroxide or a tray-based 10% carbamide peroxide/dentifrice/mouth rinse combination system. Following the manufacturer' s directions, the strip group bleached twice daily for 30 minutes, whereas the tray group bleached twice daily for 20,30 minutes, preceded by tooth brushing with a whitening dentifrice and followed by mouth rinsing with a whitening solution. Treatment extended for 14 days, with evaluation at day 7 and again at day 14. Whitening response was measured objectively as L*a*b* from standardized digital images of maxillary anterior teeth. Tolerability was assessed by oral examination and subject interview. Efficacy comparisons were made using analysis of covariance, whereas tolerability was compared using the nonparametric Wilcoxon rank-sum test. Results Both treatments resulted in statistically significant (P < 0.01) improvements from baseline for all color parameters. For between-group comparisons, the 6% hydrogen peroxide strips yielded a nearly 3-fold reduction in yellowness (,b*), a nearly 2-fold improvement in lightness (,L*), 2.6 times greater redness reduction (,a*), and a more than 2-fold change in overall color (,E*) compared to the tray-based combination system. Between-group comparisons were statistically significant for the all color parameters at both the day 7 and day 14 evaluations (P < 0.001). In general, 7-day use of the whitening strips provided significantly greater color improvement relative to the combination dentifrice/gel/rinse system at day 14. In addition, the groups differed significantly (P < 0.05) in bleaching tolerability severity-days, with the strip system demonstrating better overall tolerability compared to the combination system. Conclusions The single-step 6% hydrogen peroxide strips demonstrated better overall clinical response, in terms of both tooth-whitening efficacy and tolerability, than the multiple-step tray-based combination system. [source] Aripiprazole Effects on Alcohol Consumption and Subjective Reports in a Clinical Laboratory Paradigm,Possible Influence of Self-ControlALCOHOLISM, Issue 11 2008Konstantin Voronin Introduction:, There has been increasing interest in the use of medications that affect the dopamine receptor in the treatment of alcoholism. Aripiprazole has the unique pharmacology of being a partial dopamine agonist serving to stabilize brain dopamine systems in both frontal cortical and subcortical areas. As such, it might act to dampen alcohol reinforcement and craving and/or alter control over alcohol use. The current clinical laboratory study was conducted to evaluate the safety and efficacy of aripiprazole as a potential agent to alter drinking and objective effects of alcohol. Methods:, Thirty nontreatment seeking alcoholics were enrolled in a subacute human laboratory study and received double-blind treatment with up to 15 mg of aripiprazole (n = 15) or identical placebo (n = 15) for 8 days. Tolerability and utility of aripiprazole was monitored during natural drinking over the first 6 days of medication treatment and also during a free choice limited access alcohol consumption paradigm following an initial drink of alcohol in a bar-lab setting on Day 8. Results:, Aripiprazole was well tolerated and reduced drinking in nontreatment seeking alcoholics over 6 days of natural drinking,especially in those with lower self control (more impulsive). It also reduced drinks in the bar-lab after a priming drink and broke the link between priming drink induced stimulation and further drinking. During the bar-lab drinking session, there were no differences in subjective high, intoxication, or craving between subjects treated with aripiprazole or placebo. Discussion:, This study joins several others in demonstrating the utility of subacute dosing laboratory paradigms for evaluating medication effects in alcoholics. Aripiprazole was well tolerated and lowered alcohol use, especially in those with lower impulse control. Further study is needed to determine the safety and utility of aripiprazole in the treatment of alcoholism and if subgroups of alcoholics are more likely to respond. [source] Tolerability of Gemcitabine and Carboplatin Doublet Therapy in Cats with CarcinomasJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2009I. Martinez-Ruzafa Background: This study was performed to determine the toxicity of gemcitabine-carboplatin doublet therapy in cats with carcinomas. Hypothesis: Gemcitabine and carboplatin are safe in tumor-bearing cats. Animals: Twenty cats with spontaneously occurring carcinomas. Methods: A cohort of 6 cats received gemcitabine (2 mg/kg IV) on days 1, 8, and 15 and carboplatin (10 mg/kg IV) immediately after gemcitabine on day 1 of a 21-day cycle. A 2nd cohort of 14 cats received carboplatin 4 hours after gemcitabine on day 1 and gemcitabine on day 8 but not day 15. The cycles were repeated every 21 days. Results: Cats in the 1st cohort received a median of 3.75 cycles per animal (range, 1,6). Two cats (33.3%) developed grade 3 or 4 neutropenia, 1 (16.7%) grade 4 thrombocytopenia, and 1 (16.7%) grade 3 gastrointestinal toxicity. Gemcitabine dose reductions and treatment delays occurred in 1 and 4 cats, respectively. Cats in the 2nd cohort received a median of 2 cycles per animal (range, 0.5,10). Two cats (14.3%) had grade 3 or 4 neutropenia and 1 (7.1%) had grade 3 and 4 gastrointestinal toxicity. One cat required gemcitabine dose reduction and 6 had treatment delays. In the 2nd cohort, of 11 cats with measurable tumors, there was 1 complete response (pancreatic carcinoma) and 1 partial response (squamous cell carcinoma, receiving concurrent nonsteroidal anti-inflammatory drugs). Conclusions and Clinical Importance: Gemcitabine-carboplatin combination appears moderately well tolerated in tumor-bearing cats. Minimal patient benefit suggests that alternative schedules or combinations of gemcitabine with other agents should be explored. [source] Combination Chemotherapy in Feline Lymphoma: Treatment Outcome, Tolerability, and Duration in 23 CatsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 2 2008D. Simon Background: Different chemotherapy regimes have been described for feline lymphoma with varying outcomes. Hypothesis: In cats with lymphoma, a long-term, multiagent chemotherapy protocol will be effective and carry acceptable toxicity. Animals: Twenty-three cats with histologically or cytologically confirmed diagnosis of lymphoma. Methods: Prospective, single-arm clinical trial in which cats were treated with a chemotherapy protocol consisting of a cyclic combination of l -asparaginase, vincristine, cyclophosphamide, doxorubicin, methotrexate, and prednisolone with a planned total treatment time of 122 weeks. Results: Complete remission (CR) rate was 74% (n = 17). Fourteen percent of cats attained partial remission (PR). Median duration of first CR was 264 days (range, 45,2,485 days). Six-month, 1-, and 2,5-year remission rates were 75, 50, and 34%, respectively. Duration of PR ranged between 23 and 63 days. Median survival in cats with CR was 296 days (range, 50,2,520 days). Six-month, 1-, 2-, and 3,5-year survival rates in cats with CR were 82, 47, 34, and 27%, respectively. Survival of cats achieving PR ranged between 38 and 120 days. Of the analyzed variables, only anatomical location had a significant influence on remission duration (P=.022). Actual median treatment time in cats with CR was 128 days (18 weeks). Hematologic and gastrointestinal toxicosis was infrequent and mostly low grade. Conclusions and Clinical Importance: In this population of cats with lymphoma, chemotherapy was effective. With infrequent and mostly low-grade toxicosis, tolerability of the protocol may be considered good. [source] Titration with Oxymorphone Extended Release to Achieve Effective Long-Term Pain Relief and Improve Tolerability in Opioid-Naive Patients with Moderate to Severe PainPAIN MEDICINE, Issue 7 2008Richard Rauck MD ABSTRACT Objective., Assess the effectiveness and tolerability of a program of gradual dose titration with oxymorphone extended release (ER) for treatment of moderate to severe chronic pain in opioid-naive patients. Design., Open-label, nonrandomized 6-month study with a titration/stabilization period of ,1 month followed by a 5-month maintenance period. Setting., Multidisciplinary pain centers in the United States. Patients., Adult opioid-naive patients with moderate to severe chronic pain. Interventions., Patients were gradually titrated from a 5-mg dose of oxymorphone ER (taken every 12 hours) to a stabilized dose that provided effective pain relief and was well tolerated. Outcome Measures., Brief Pain Inventory Short Form questions 5 and 9, patient and physician global assessments of pain relief, adverse events (AEs), and discontinuations. Results., The majority (94/126; 75%) of patients were stabilized on a dose of oxymorphone ER that provided effective pain relief with tolerable AEs. Most (81/94; 86%) required <24 days to reach a stable dose. Sixteen percent of patients in the titration period and 17% of patients in the maintenance period discontinued because of AEs possibly or probably related to oxymorphone ER. Patients completing the entire 5-month maintenance period experienced effective pain relief with significant (>50%) reductions of pain interference with quality-of-life measures. There was minimal dose escalation over the 5 months and low use of rescue medication. Conclusions., Oxymorphone ER provided effective pain relief from moderate to severe chronic pain in opioid-naive patients. Gradual titration was well tolerated, with a low rate of discontinuations caused by AEs. [source] Low Systemic Absorption and Good Tolerability of Pimecrolimus, Administered as 1% Cream (Elidel®) in Infants with Atopic Dermatitis , A Multicenter, 3-Week, Open-Label StudyPEDIATRIC DERMATOLOGY, Issue 5 2005Doris Staab M.D. Here we evaluate pimecrolimus blood concentrations and tolerability to pimecrolimus cream 1% in 22 infants below 2 years of age with atopic dermatitis (10,92% body surface area affected at baseline). Efficacy was assessed as a secondary objective. Pimecrolimus cream 1% was applied twice daily for 3 weeks. Blood concentrations were low, typically (96% of total 100 concentrations measured) below 2 ng/mL, the majority (71%) remaining below 0.5 ng/mL. The highest concentration observed was 2.26 ng/mL. At steady state, there was no indication of accumulation. Pimecrolimus was well tolerated locally and systemically, with no serious adverse events recorded. Most adverse events recorded (35 in 17/22 patients) were typical of the young pediatric population studied, of mild to moderate severity, and not considered to be study-medication related, with the exception of four local adverse effects limited to the site of cream application. No clinically relevant change was observed in physical examination, vital signs, or laboratory safety parameters. A rapid onset of therapeutic effect was observed within the first four days of treatment. Pimecrolimus cream 1% is well tolerated in infants 3 to 23 months of age treated for 3 weeks, and results in minimal systemic exposure. [source] A randomized, multicentre, open-label, parallel-group trial to compare the efficacy and safety profile of daming capsule in patients with hypercholesterolemiaPHYTOTHERAPY RESEARCH, Issue 7 2009Ai Jing Abstract To study the efficacy and tolerability of Daming capsule (DMC) in Chinese patients with hyperlipidemia, a randomized, multi-centre, open-label, parallel-group trial was conducted. Sixty enrolled patients with hyperlipidemia allocated to six medical centers were randomly divided into two groups of 30 individuals each. One group received DMC 2 g b.i.d. for 6 weeks, and the other received pravastatin 10 mg o.d. for 6 weeks. For efficacy assessment, serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were measured before and after drug treatment. Serum TC and LDL-C levels in the DMC-treatment group were significantly decreased compared with those before treatment (p < 0.05), while TG and HDL-C levels did not change much. Tolerability was assessed by heart rate (HR), blood pressure (BP), body mass index (BMI), alanine aminotransferase (ALT) and creatinine (Cr), which were not changed in either the DMC or pravastatin groups at 3 and 6 weeks (p > 0.05). Besides, eight patients experienced diarrhea during DMC treatment and two experienced myalgia and epigastric discomfort during pravastatin treatment. Based on the above results, it was concluded that DMC may be a good candidate for the treatment of hyperlipidemia and further clinical trials are warranted. Copyright © 2009 John Wiley & Sons, Ltd. [source] | ||||||||||||||||||||||||||||||||||||||||||||||