Relationship Between Peak Troponin Values and Long-Term Ischemic Events Among Medically Managed Patients With Acute Coronary Syndromes.

Background: The relationship between troponin level and outcomes among patients with non-ST-segment elevation ACS is established, but the relationship of troponin level with long-term outcomes among medically managed non-ST-segment elevation ACS patients receiving contemporary antiplatelet therapy is inadequately defined.

Methods And Results: In 6763 medically managed non-ST-segment elevation ACS patients randomized in TRILOGY ACS (Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes) (prasugrel versus clopidogrel), we examined relationships between categories of peak troponin/upper limit of normal (ULN) ratio within 48 hours of the index ACS event (≈4.5 days before randomization) and 30-month outcomes (cardiovascular death, myocardial infarction, or stroke; cardiovascular death or myocardial infarction; and all-cause death).

Applying novel methods to assess clinical outcomes: insights from the TRILOGY ACS trial.

Aims: Several methods provide new insights into understanding clinical trial composite endpoints, using both conventional and novel methods. The TRILOGY ACS trial is used as a contemporary example to prospectively compare these methods side by side.

Methods And Results: The traditional time-to-first-event, Andersen-Gill recurrent events method, win ratio, and a weighted composite endpoint (WCE) are compared using the randomized, active-control TRILOGY ACS trial.

Prasugrel versus clopidogrel for acute coronary syndromes without revascularization.

Background: The effect of intensified platelet inhibition for patients with unstable angina or myocardial infarction without ST-segment elevation who do not undergo revascularization has not been delineated.

Methods: In this double-blind, randomized trial, in a primary analysis involving 7243 patients under the age of 75 years receiving aspirin, we evaluated up to 30 months of treatment with prasugrel (10 mg daily) versus clopidogrel (75 mg daily). In a secondary analysis involving 2083 patients 75 years of age or older, we evaluated 5 mg of prasugrel versus 75 mg of clopidogrel.

Failed efficacy of fluoxetine in the treatment of posttraumatic stress disorder: results of a fixed-dose, placebo-controlled study.

A multicenter, double-blind, 12-week, placebo-controlled trial of 411 randomized patients, predominantly women diagnosed with posttraumatic stress disorder, failed to show a difference between either dose of fluoxetine treatment and placebo. The mean changes from baseline (SD) measured by the Clinician-Administered PTSD Scale scores were -42.9 (23.

Olanzapine versus risperidone in the treatment of manic or mixed States in bipolar I disorder: a randomized, double-blind trial.

Objective: To compare olanzapine and risperidone in the treatment of nonpsychotic acute manic or mixed episodes.

Method: This 3-week, randomized, controlled, double-blind, parallel multicenter study compared olanzapine (5-20 mg/day; N = 165) and risperidone (1-6 mg/day; N = 164) among hospital inpatients who met DSM-IV criteria for bipolar I disorder, manic or mixed episode, without psychotic features. The study was conducted at 30 sites in the United States between July 2001 and June 2002.

A 7-week, randomized, double-blind trial of olanzapine/fluoxetine combination versus lamotrigine in the treatment of bipolar I depression.

Objective: Determine the efficacy and tolerability of olanzapine/fluoxetine combination (OFC) for treatment of acute bipolar I depression compared with lamotrigine.

Method: The 7-week, acute phase of a randomized, double-blind study compared OFC (6/25, 6/50, 12/25, or 12/50 mg/day; N = 205) with lamotrigine ([LMG] titrated to 200 mg/day; N = 205) in patients with DSM-IV-diagnosed bipolar I disorder, depressed. The study was conducted from November 2003 to August 2004.

Fluoxetine 40-60 mg versus fluoxetine 20 mg in the treatment of children and adolescents with a less-than-complete response to nine-week treatment with fluoxetine 10-20 mg: a pilot study.

Objective: The aim of this study was to compare fluoxetine dosage titration to 40-60 mg/day with fixed fluoxetine 20-mg/day treatment for an additional 10 weeks in pediatric outpatients with major depressive disorder (MDD) who had not met protocol-defined response criteria after 9-week acute fluoxetine treatment.

Methods: Patients unresponsive (less than or equal to 30% decrease in Children's Depression Rating Scale-Revised [CDRS-R] score) after 9-week fluoxetine treatment were randomly reassigned to continue at 20 mg/day or to increase to 40 mg/day. After 4 weeks, patients unresponsive to 40 mg/day could receive 60 mg/day.

Safety of subchronic treatment with fluoxetine for major depressive disorder in children and adolescents.

Objective: The aim of this study was to assess the safety of subchronic fluoxetine treatment for major depressive disorder (MDD) in children and adolescents.

Methods: Patients received up to 19 weeks of treatment with fluoxetine, 10 mg-60 mg daily. Safety was evaluated through the reporting of concomitant medications, vital signs, routine laboratory testing, electrocardiograms (ECGs), and adverse event data.

Duloxetine 60 mg once-daily in the treatment of painful physical symptoms in patients with major depressive disorder.

Background: While emotional symptoms such as depressed mood and loss of interest have traditionally been considered to constitute the core symptoms of major depressive disorder (MDD), the prevalence and importance of painful physical symptoms such as back pain, abdominal pain, and musculoskeletal pain is becoming increasingly appreciated. Antidepressants possessing dual serotonin/norepinephrine (5-HT/NE) reuptake inhibition may demonstrate greater efficacy in the alleviation of pain. The efficacy of duloxetine, a balanced and potent dual reuptake inhibitor of 5-HT and NE, was evaluated within a cohort of depressed patients with associated painful physical symptoms.

Recurrence of symptoms of premenstrual dysphoric disorder after the cessation of luteal-phase fluoxetine treatment.

Objective: The aim of this study was to use the data from two clinical trials to evaluate premenstrual dysphoric disorder symptom severity after the discontinuation of fluoxetine treatment.

Study Design: A retrospective analysis of two clinical trials was performed. Patients were treated with fluoxetine or placebo for three cycles, with the use of several different dosing regimens, followed by single blind placebo treatment for one cycle.

Fluoxetine v. placebo in prevention of relapse in post-traumatic stress disorder.

Background: Little is known about the effect of pharmacotherapy in the prevention of post-traumatic stress disorder (PTSD) relapse.

Aims: To assess the efficacy and tolerability of fluoxetine in preventing PTSD relapse.

Method: This was a double-blind, randomised, placebo-controlled study.

Safety and efficacy of fluoxetine in patients who receive oral contraceptive therapy.

Objective: Because many women who receive pharmacologic therapy with antidepressants are also prescribed oral contraceptives, it is important to assess the risk of clinically significant drug interactions. We reviewed the United States fluoxetine clinical trial database, specifically analyzing women ages 18 to 45 years, for differences in safety, antidepressant efficacy, and unplanned pregnancies that were associated with oral contraceptive use.

Study Design: Data from 17 double-blind, placebo-controlled clinical trials in 1698 women were analyzed retrospectively.

Switching patients from daily citalopram, paroxetine, or sertraline to once-weekly fluoxetine in the maintenance of response for depression.

Background: Major depressive disorder is frequently a chronic, recurrent condition necessitating maintenance treatment. For some patients, compliance with daily pharmacotherapy is difficult over time. As an alternative approach, a once-weekly administered formulation of fluoxetine has recently been made available.

Fluoxetine versus placebo in posttraumatic stress disorder.

Background: This study was designed to address the efficacy and tolerability of fluoxetine in patients with posttraumatic stress disorder (PTSD) as diagnosed using the Structured Clinical Interview for DSM-IV Axis I Disorders and the Clinician-Administered PTSD Scale (CAPS). The patient population included both civilians and combat veterans.

Method: This was a double-blind, randomized, placebo-controlled study conducted in Europe, Israel, and South Africa, primarily in war-torn countries.