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Target Dose (target + dose)

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Medical Sciences	88%

Selected Abstracts

Baseline Characteristics of Patients Randomized in the Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) Study

CONGESTIVE HEART FAILURE, Issue 2 2008
Cecilia Linde MD
The Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) study is a randomized controlled trial currently assessing the safety and efficacy of cardiac resynchronization therapy in patients with asymptomatic left ventricular (LV) dysfunction with previous symptoms of mild heart failure. This paper describes the baseline characteristics of randomized patients; 610 patients with New York Heart Association (NYHA) class II (82.3%) heart failure or asymptomatic (NYHA class I) LV dysfunction with previous symptoms (17.7%) were randomized in 73 centers. The mean age was 62.5±11.0 years, the mean LV ejection fraction was 26.7%±7.0%, and the mean LV end-diastolic diameter was 66.9±8.9 mm. A total of 97% of patients were taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and 95.1% were taking ,-blockers, which were at the target dose in 35.1% of patients. Compared with previous randomized cardiac resynchronization therapy trials, REVERSE patients are on better pharmacologic treatment, are younger, and have a narrower QRS width despite similar LV dysfunction. [source]

Effect of Bisoprolol on Right Ventricular Function and Brain Natriuretic Peptide in Patients With Heart Failure

CONGESTIVE HEART FAILURE, Issue 3 2004
Luís Beck-da-Silva MD
Beta-blocker use improves left ventricular ejection fraction (LVEF) in patients with heart failure. A similar effect of , blockers on right ventricular function has been proposed, although the effect of bisoprolol, a highly selective ,-1 blocker, on right ventricular function has not been assessed. This study investigated the short-term effect of bisoprolol on right ventricular function in chronic heart failure patients. A cohort of 30 heart failure patients who were not taking , blockers at baseline was studied prospectively. Right ventricular ejection fraction (RVEF) and LVEF were measured at both baseline and 4 months by radionuclide angiography. Bisoprolol was up-titrated during four monthly visits by a preestablished protocol to a target dose of 10 mg/d. The dose of vasodilators was not changed. Quality of life and brain natriuretic peptide level were assessed. Mean age was 62.7±14.3 years. Baseline RVEF was 30.7%±6.3% and baseline LVEF was 21.7%±9.4%. Mean bisoprolol dose reached was 5.3±3.9 mg daily. At 4 months, RVEF significantly increased by 7.1 % (95% confidence interval, 3.9,10.2; p=0.0001) and LVEF also increased significantly by 7.9% (95% confidence interval, 4.0%,11.9%p=0.0003). Quality-of-life score improved from 42.8 to 30.8 (p=0.047). No correlation was found between brain natriuretic peptide levels and RVEF. Bisoprolol treatment for 4 months resulted in a significant improvement of RVEF, which paralleled the improvement of LVEF. [source]

Gabapentin Increases Slow-wave Sleep in Normal Adults

EPILEPSIA, Issue 12 2002
Nancy Foldvary-Schaefer
Summary: ,Purpose: The older antiepileptic drugs (AEDs) have a variety of effects on sleep, including marked reduction in rapid-eye-movement (REM) sleep, slow-wave sleep (SWS), and sleep latency, and an increase in light sleep. The effects of the newer AEDs on sleep are unknown. Our purpose was to study the effect of gabapentin (GBP) on sleep. Methods: Ten healthy adults and nine controls were the subjects of this study. All underwent baseline and follow-up polysomnography (PSG) and completed sleep questionnaires. After baseline, the treated group received GBP titrated to 1,800 mg daily. Polygraphic variables and Epworth Sleepiness Scale (ESS) scores, a subjective measure of sleep propensity, were compared by using the Wilcoxon signed rank test. Results: Nine of the treated subjects achieved the target dose; one was studied with 1,500 mg daily because of dizziness experienced at the higher dose. GBP-treated subjects had an increase in SWS compared with baseline. No difference in the ESS or other polygraphic variables was observed. However, a minor reduction in arousals, awakenings, and stage shifts was observed in treated subjects. Conclusions: GBP appears to be less disruptive to sleep than are some of the older AEDs. These findings may underlie the drug's therapeutic effect in the treatment of disorders associated with sleep disruption. [source]

Efficacy and Safety of Levetiracetam in Children with Partial Seizures: An Open-label Trial

EPILEPSIA, Issue 5 2002
Tracy A. Glauser
Summary: ,Purpose: To assess the efficacy and safety of levetiracetam (LEV) as adjunctive therapy in children with treatment-resistant partial-onset seizures. Methods: Children (aged 6,12 years) with treatment-resistant partial-onset seizures receiving one standard antiepileptic drug (AED) were eligible. After a 4-week baseline period, children received LEV in a 6-week titration phase (target dose, 40 mg/kg/day) followed by an 8-week evaluation phase. Seizure frequency during the evaluation period with individualized LEV doses (20,40 mg/kg/day) were compared with the 4-week baseline seizure frequency. Plasma concentrations of LEV and other AEDs were determined to evaluate potential drug interactions. Results: Twenty-four subjects enrolled and received LEV; 23 entered the evaluation phase, and 22 completed the evaluation phase. Compared with their baseline seizure frequency, 12 (52%) of 23 subjects entering the evaluation phase had their seizure frequency decrease by >50%. Two subjects remained seizure free during the entire evaluation period. LEV did not significantly affect plasma concentrations of any concomitant AED during this study, and no alteration of mean clinical laboratory values was observed. The most commonly reported adverse events were headache, infection, anorexia, and somnolence. Conclusions: This open-label study of adjunctive LEV therapy (at 20,40 mg/kg/day) suggests that LEV is effective, safe, and well tolerated in children ages 6,12 years with treatment-resistant partial-onset seizures. A randomized, placebo-controlled, double-blind trial of LEV adjunctive therapy in children with treatment-resistant partial-onset seizures is needed and ongoing to confirm these open-label findings. [source]

Clinical impact of FDG-PET/CT in the planning of radiotherapy for early-stage Hodgkin lymphoma

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2007
Martin Hutchings
Abstract Background:,Early-stage Hodgkin lymphoma (HL) has excellent survival rates but carries a high risk of late treatment-related adverse effects. Modern, individualised therapeutic strategies require an accurate determination of the extent of the disease. This study investigated the potential impact of 2-[18F]-fluoro-2-deoxy- d -glucose positron emission tomography/computerised tomogrpahy (FDG-PET/CT) in the planning of involved field radiotherapy (IFRT). Patients and methods:,Thirty patients received staging FDG-PET/CT before therapy, and IFRT after a short course of ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) chemotherapy. IFRT planning was performed using only the CT data from the FDG-PET/CT scan. Later, the IFRT planning was performed anew using the FDG-PET/CT data as basis for contouring. Results:,In 20 out of 30 patients, the radiotherapy (RT) course was unaffected by the addition of FDG-PET/CT. FDG-PET/CT would have increased the irradiated volume in seven patients where the volume receiving a minimum of 90% of the target dose was increased by 8,87%. FDG-PET/CT decreased the volume in two patients where the volume was reduced by 18% and 30%. Conclusions:,When used for RT planning, FDG-PET/CT results in larger IFRT treatment volumes. If FDG-PET/CT is introduced to RT planning, the method should be accompanied by a change in RT treatment strategy, aiming at more targeted therapy in order to best avoid radiation to normal tissues. [source]

Chronic high dose transdermal nicotine in Parkinson's disease: an open trial

EUROPEAN JOURNAL OF NEUROLOGY, Issue 12 2007
G. Villafane
Whether nicotine has therapeutic effects on Parkinson's disease (PD) symptoms is controversial, but high doses and chronic treatment have never been tested. We report the results of a pilot, open-label trial to assess the safety and possible efficacy of chronic high doses of nicotine. Six patients with advanced idiopathic PD received increasing daily doses of transdermal nicotine up to 105 mg/day over 17 weeks. All patients but one accepted the target dose. Nausea and vomiting were frequent but moderate, and occurred in most of the patients (four of six) who received over 90 mg/day and 14 weeks of nicotine treatment. During the plateau phase, patients improved their motor scores and dopaminergic treatment was reduced. These results confirm the feasibility of chronic high dose nicotinic treatment in PD but warrant validation of the beneficial effects by a randomized controlled trial. [source]

Undertreatment of congestive heart failure in an Australian setting

JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 1 2004
P. J. Boyles BPharm (Hons)
Summary Aim:, Guidelines for the management of patients with chronic heart failure have undergone change in recent years, with , -blockers and spironolactone shown to reduce mortality when added to angiotensin converting enzyme (ACE) inhibitors, diuretics and digoxin. The aim of this study was to examine the therapeutic management of heart failure in patients admitted to Tasmania's three major public hospitals, with an assessment of the appropriateness of the therapy according to contemporary published guidelines. Methods:, An extensive range of clinical and demographic data was retrospectively extracted from the medical records of consecutive adult patients admitted to the medical wards of the hospitals with heart failure, either as a primary diagnosis or as a comorbidity, during a 6-month period in late 1999,early 2001. Results:, The 450 patients (57% females) had a mean age of 77·8 ± 10·2 years, and were being treated with a median of seven drugs on hospital admission. The percentages of patients being treated with the major drugs of interest were: ACE inhibitors (50%), , -blockers (22%), spironolactone (15%), digoxin (24%), loop diuretics (65%) and angiotensin-II receptor antagonists (8%). Almost 10% were taking a non-steroidal anti-inflammatory agent. Less than one-half the patients who were receiving an ACE inhibitor were taking a target dose for heart failure. There were no significant differences in the pattern of drug use between the three hospitals. Underuse of heart failure medications was most pronounced in women and elderly patients. Conclusions:, The data suggest that current guidelines for the treatment of heart failure are still not being reflected in clinical practice. The relatively low use of drugs shown to improve survival in heart failure is of concern and warrants educational intervention. [source]

Improved guideline adherence to pharmacotherapy of chronic systolic heart failure in general practice , results from a cluster-randomized controlled trial of implementation of a clinical practice guideline

JOURNAL OF EVALUATION IN CLINICAL PRACTICE, Issue 5 2008
Frank Peters-Klimm MD
Abstract Rationale and aims, Clinical practice guidelines (CPG) reflect the evidence of effective pharmacotherapy of chronic (systolic) heart failure (CHF) which needs to be implemented. This study aimed to evaluate the effect of a new, multifaceted intervention (educational train-the-trainer course plus pharmacotherapy feedback = TTT) compared with standard education on guideline adherence (GA) in general practice. Method, Thirty-seven participating general practitioners (GPs) were randomized (18 vs. 19) and included 168 patients with ascertained symptomatic CHF [New York Heart Association (NYHA) II-IV]. Groups received CPG, the TTT intervention consisted of four interactive educational meetings and a pharmacotherapy feedback, while the control group received a usual lecture (Standard). Outcome measure was GA assessed by prescription rates and target dosing of angiotensin converting enzyme (ACE) inhibitors (ACE-I) or angiotensin receptor blockers (ARB), beta-blockers (BB) and aldosterone antagonists (AA) at baseline and 7-month follow-up. Group comparisons at follow-up were adjusted to GA, sex, age and NYHA stage at baseline. Results, Prescription rates at baseline (n = 168) were high (ACE-I/ARB 90, BB 79 and AA 29%) in both groups. At follow up (n = 146), TTT improved compared with Standard regarding AA (43% vs. 23%, P = 0.04) and the rates of reached target doses of ACE-I/ARB (28% vs. 15%, P = 0.04). TTT group achieved significantly higher mean percentages of daily target dose (52% vs. 42%, mean difference 10.3%, 95% CI 0.84,19.8, P = 0.03). Conclusion, Despite of pre-existing high GA in both groups and an active control group, the multifaceted intervention was effective in quality of care measured by GA. Further research is needed on the choice of interventions in different provider populations. [source]

A Pilot Trial of the Alpha-1 Adrenergic Antagonist, Prazosin, for Alcohol Dependence

ALCOHOLISM, Issue 2 2009
Tracy L. Simpson
Background:, Current medications for alcohol dependence (AD) show only modest efficacy. None target brain noradrenergic pathways. Theory and preclinical evidence suggest that noradrenergic circuits may be involved in alcohol reinforcement and relapse. We therefore tested the ,-1 adrenergic receptor antagonist, prazosin, as a pharmacotherapy for AD. Methods:, We randomized 24 participants with AD but without posttraumatic stress disorder to receive either prazosin or placebo in a 6-week, double-blind pilot study. Medication was titrated to a target dose of 4 mg QAM, 4 mg QPM, and 8 mg QHS by the end of week 2. Participants received 5 medical management treatment sessions. Participants were reminded 3 times each day via a text pager to take medications and to call a telephone monitoring system once daily to provide self-reports of alcohol consumption and craving, the primary outcome measures. Results were analyzed using mixed linear regression adjusted for drinking days per week at baseline and week number. Results:, Twenty of the 24 (83%) subjects completed. Among the completers, the prazosin group reported fewer drinking days per week than the placebo group during the final 3 weeks of the study. Since only 1 woman was randomized to placebo and only three women completed the trial, the following results focus on the 17 male completers. The prazosin group reported fewer drinking days per week and fewer drinks per week during the final 3 weeks of the study; average total number of drinking days for the placebo group 5.7 (SEM 1.9) versus 0.9 (SEM 0.5) for the prazosin group, and average total number of drinks 20.8 (SEM 6.5) for the placebo group versus 2.6 (SEM 1.3) for the prazosin group. Rates of adverse events were equivalent across conditions. Conclusions:, Prazosin holds promise as a pharmacologic treatment for AD and deserves further evaluation in a larger controlled trial. [source]

Pilot study of pentoxifylline in hepatopulmonary syndrome,

LIVER TRANSPLANTATION, Issue 8 2008
Rajasekhar Tanikella
Hepatopulmonary syndrome (HPS) results when chronic liver disease or portal hypertension causes intrapulmonary microvascular dilatation with hypoxemia. In experimental HPS, tumor necrosis factor alpha (TNF-,) overproduction contributes to vasodilatation, which is improved by pentoxifylline, a TNF-, inhibitor. The effectiveness of pentoxifylline in humans is unknown. The aim of this open-label, single-arm clinical trial was to assess the efficacy and tolerability of pentoxifylline in patients with cirrhosis and advanced HPS undergoing liver transplantation evaluation. Nine adults with cirrhosis and moderate to severe HPS were enrolled. All patients had an initial 2-week titration to a target dose of pentoxifylline of 400 mg by mouth every 8 hours, which was continued for 6 weeks. Baseline and follow-up arterial blood gases and TNF-, levels were evaluated. Adverse effects and tolerability were assessed. The 9 patients had a mean age of 55 ± 10 years, and 67% were female. The most common causes of cirrhosis were hepatitis C virus and alcohol (55%). The mean Model for End-Stage Liver Disease score was 11 (range, 6-19), and patients had advanced hypoxemia [mean partial pressure of arterial oxygen (PaO2) = 54 ± 12 mm Hg, mean alveolar-arterial oxygen gradient (A-a PaO2) = 57 ± 15 mm Hg]. Of the 9 patients enrolled, follow-up blood gases were done in 7. There was no significant change in PaO2 (P = 0.3) or A-a PaO2 (P = 0.3) with treatment. Pentoxifylline was poorly tolerated. Nausea (100%) and vomiting (56%) were the predominant side effects, and only a single patient was able to complete full-dose therapy. Treatment with pentoxifylline did not improve arterial oxygenation in advanced HPS, and tolerance was limited by gastrointestinal toxicity. Liver Transpl 14:1199,1203, 2008. © 2008 AASLD. [source]

Levetiracetam in patients with cortical myoclonus: A clinical and electrophysiological study,

MOVEMENT DISORDERS, Issue 12 2005
Pasquale Striano MD
Abstract Levetiracetam is a new antiepileptic agent that exerts antimyoclonic effects. We conducted an open-label trial to evaluate the effect of levetiracetam in chronic cortical myoclonus of diverse etiologies and to determine whether levetiracetam affects electrophysiological findings. Sixteen patients, aged between 19 and 72 years, with refractory, chronic, cortical myoclonus were recruited. We assessed myoclonus severity with the Unified Myoclonus Rating Scale (UMRS). The electrophysiological study comprised jerk-locked averaging, somatosensory evoked potentials (SEPs), and long loop reflex I. Levetiracetam was administered add-on at a starting dose of 500 mg twice per day up to the target dose of 50 mg/kg/day. Patients were reevaluated clinically and electrophysiologically 2 weeks after the titration phase. Fourteen patients completed the trial. Posttreatment UMRS scores showed an improvement of myoclonus in all cases. Pretreatment, 9 patients had "giant" SEPs. Posttreatment, the amplitude of these SEPs was reduced by more than 50% in 3 of 9 patients, and the mean N20-P25 amplitude was reduced significantly. Pre- and posttreatment SEP amplitude was not related to myoclonus severity or duration. Levetiracetam is a promising and a relatively easy-to-test antimyoclonic agent, which has the potential to improve significantly the patient's disability; however, its long-term efficacy should be verified in larger controlled studies. © 2005 Movement Disorder Society [source]

Effects of gamma irradiation on the life stages of yellow flower thrips, Frankliniella schultzei (Trybom) (Thysanoptera: Thripidae)

ANNALS OF APPLIED BIOLOGY, Issue 3 2001
JULIANA A YALEMAR
Summary Irradiation at a minimum absorbed dose of 250 Grays (Gy) has been approved by the USDA as a quarantine treatment for certain fruits in Hawaii to control four species of tephritid fruit flies. Subsequent research must determine whether this dose is sufficient to control other quarantine pests, such as mealybugs, thrips, mites, beetles, moths, and scale insects, on other commodities with export potential that are approved for irradiation treatment for fruit flies. This study demonstrated that irradiation at 250 Gy caused non-emergence of eggs and pupae, failure of larval development, and sterility of adults of yellow flower thrips, Frankliniella schultzei (Trybom). Adults were the most resistant stage tested, with 100% mortality at 57, 36 and 30 days post-treatment for the 250, 350 and 400 Gy treatments, respectively. Untreated adults survived up to 66 days. After receiving an irradiation dose of 250 Gy, no one- to two-day old eggs hatched successfully, while 3,4-day old eggs hatched but did not develop beyond the larval stage. Of the controls, 96.0% of 1,2-day old eggs and 75.9% of the 3,4-day old eggs hatched and survived through pupation. No first or second instar larvae treated with a target dose of 250 Gy were able to pupate. When pupae were irradiated at 250 Gy, 37% emerged as adults and all were sterile compared to 88.3% emergence of controls. [source]

Dose Finding for Continuous and Ordinal Outcomes with a Monotone Objective Function: A Unified Approach

BIOMETRICS, Issue 1 2009
Anastasia Ivanova
Summary In many phase I trials, the design goal is to find the dose associated with a certain target toxicity rate. In some trials, the goal can be to find the dose with a certain weighted sum of rates of various toxicity grades. For others, the goal is to find the dose with a certain mean value of a continuous response. In this article, we describe a dose-finding design that can be used in any of the dose-finding trials described above, trials where the target dose is defined as the dose at which a certain monotone function of the dose is a prespecified value. At each step of the proposed design, the normalized difference between the current dose and the target is computed. If that difference is close to zero, the dose is repeated. Otherwise, the dose is increased or decreased, depending on the sign of the difference. [source]

Exploring efficacy and tolerability outcomes in patients with difficult-to-treat epilepsy receiving adjunctive topiramate at different titration rates , an exploratory study

ACTA NEUROLOGICA SCANDINAVICA, Issue 2 2009
C. Kurth
Objective,,, To compare rapid vs regular titration of topiramate concerning efficacy and safety. Materials and methods,,, Open-label, prospective, single-center study exploring efficacy and tolerability of two adjunctive dosing regimens of topiramate (TPM) in adult patients with difficult-to-treat epilepsy. Based on investigator judgment, 21 of 50 consecutive patients received a rapid titration (starting dose 50 mg/day, stepwise increase with 50 mg/day after 3 days each until reaching the target dose), while the other 29 patients received titration according to the German prescribing information (starting dose 25 mg/day, stepwise increase with 25,50 mg/day every 7 days). Patients were observed until the target dose was reached and 3 months thereafter. Results,,, Mean final dosages were 136 mg/day (regular titration) and 213 mg/day (rapid titration). Efficacy and tolerability measures did not differ significantly. Forty-six percent of all patients experienced a seizure reduction of ,50%; 14% became seizure free. No serious adverse events occurred. The most common adverse effects were tiredness (20%), memory and language difficulties (18% each), slowness in thinking and speech (10%), psychomotor disturbance (8%) and paresthesia (8%). Conclusions,,, This study suggests that rapid and conventional titration generate similar tolerability, safety and effectiveness in selected patients. [source]

A pooled analysis of adjunctive topiramate in refractory partial epilepsy

ACTA NEUROLOGICA SCANDINAVICA, Issue 1 2003
K. Peeters
Objectives , To evaluate the impact of different dosages of topiramate (TPM) add-on to stable antiepileptic therapy for refractory partial epilepsy in adults. Material and methods , Pooled intention-to-treat analysis of six similarly designed double-blind, placebo-controlled trials, including 481 patients treated with doses of TPM 200, 400, 600 and 800 mg/day, and 265 patients receiving placebo. Results , Seizures were reduced by ,50% from baseline in 41% of TPM-treated patients and 15% of placebo-treated patients (P < 0.001); 5 and 0.8%, respectively, were seizure-free (P < 0.003). TPM was significantly better than placebo regardless of gender, age, baseline seizure rate as well as number and type of concomitant antiepileptic drugs. Efficacy was statistically significant in favour of TPM at all dose levels: at least 50% seizure reduction was achieved in 40% of patients with 200 mg, 41% with 400 mg, 44% with 600 mg and 41% with 800 mg TPM when compared with 15% with placebo (P , 0.001 for each dosage arm vs placebo). The median reduction in monthly seizure frequency was 38%, 42%, 45% and 38% vs 8%, respectively (P , 0.001). Moreover, response to TPM was significantly superior to placebo at each of the dose levels tested for most of the baseline variables. The total percentage of withdrawals increased with the dosage, and the withdrawals caused by adverse events increased from 3% with placebo to 7% with 200 mg TPM (not significant vs placebo), 15% with 400 mg TPM (P = 0.08), 16% with 600 mg TPM (P = 0.002) and 15% with 800 mg TPM (P = 0.003). Conclusion , The efficacy of TPM add-on in partial epilepsy is consistent across efficacy endpoints and independent of study population characteristics. The response at 200 mg TPM is similar to the response at higher doses, but as drop-outs caused by adverse events are more frequent above the 200 mg dose, this pooled analysis supports that 200 mg daily is a good target dose for add-on therapy in most patients with partial epilepsy, showing an excellent balance between efficacy and tolerability. [source]

Improved guideline adherence to pharmacotherapy of chronic systolic heart failure in general practice , results from a cluster-randomized controlled trial of implementation of a clinical practice guideline

Electronic e-isotretinoin prescription chart: Improving physicians' adherence to isotretinoin prescription guidelines

AUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 2 2009
Mark BY Tang
ABSTRACT Oral isotretinoin is a highly effective treatment for refractory nodulocystic acne. However, it can be associated with serious adverse effects such as teratogenicity and hepatitis. Inadequate cumulative dosing may also result in reduced therapeutic efficacy and higher disease relapse. A preliminary audit had previously revealed a poor and inconsistent adherence to local isotretinoin prescribing guidelines by physicians. To achieve greater than 90% adherence to isotretinoin guidelines for all acne patients prescribed systemic isotretinoin at the National Skin Centre, Singapore, key areas and the reasons for non-adherence were identified. A specifically designed ,one-stop' electronic isotretinoin chart was launched within the electronic medical records (EMR) system to address important safety areas; namely, informed patient consent, pregnancy testing, baseline laboratory tests, and automatic calculation of cumulative and target doses of isotretinoin. Physician adherence to prescribing guidelines improved from a baseline of 50,60% to greater than 90% (range 95,100%) for 30 consecutive months post intervention. The e-isotretinoin chart has resulted in significant improvement in physicians' adherence to isotretinoin prescription guidelines and highlights the utility of EMR technology in influencing safe prescribing behaviour among doctors. [source]

Topiramate monotherapy in the management of acute mania: results of four double-blind placebo-controlled trials

BIPOLAR DISORDERS, Issue 1 2006
Stuart F Kushner
Objective:, To evaluate the efficacy and tolerability of topiramate monotherapy in adults with acute manic or mixed episodes of bipolar I disorder. Methods:, In four trials, adults hospitalized with acute mania, a diagnosis of bipolar I disorder, history of ,1 previous manic or mixed episodes, and ,20 Young Mania Rating Scale (YMRS) score were randomized to double-blind treatment with topiramate (target doses: 200, 400, or 600 mg/day) or placebo; two trials included an active comparator (lithium, 1500 mg/day). The core study duration in all trials was 3 weeks; three trials also had 9-week double-blind extensions. The primary efficacy variable was mean change from baseline in YMRS in the core 3-week study. Results:, Changes in YMRS score during 3 weeks were not significantly different for topiramate versus placebo (mean YMRS reductions, ,5.1 to ,8.4). Mean YMRS reductions in lithium-treated groups were significantly greater (p , 0.001 versus placebo and topiramate). A similar pattern was observed after 12 weeks of double-blind treatment in studies with double-blind extensions. Paresthesia, appetite decrease, dry mouth, and weight loss were more frequently associated with topiramate than with placebo. Conclusions:, These studies do not support the efficacy of topiramate as monotherapy in acute mania or mixed episodes in adults with bipolar I disorder. Topiramate was not associated with mood destabilization measured as mania exacerbation or treatment-emergent depression. Lithium was confirmed as an effective therapy in this population. [source]