Relating Spontaneously Reported Extrapyramidal Adverse Events to Movement Disorder Rating Scales.

Background: While antipsychotic-induced extrapyramidal symptoms (EPS) and akathisia remain important concerns in the treatment of patients with schizophrenia, the relationship between movement disorder rating scales and spontaneously reported EPS-related adverse events (EPS-AEs) remains unexplored.

Methods: Data from four randomized, placebo- and haloperidol-controlled ziprasidone trials were analyzed to examine the relationship between spontaneously reported EPS-AEs with the Simpson Angus Scale (SAS) and Barnes Akathisia Rating Scale (BARS). Categorical summaries were created for each treatment group to show the frequencies of subjects with EPS-AEs in each of the SAS and BARS categories at weeks 1, 3, and 6, and agreement between ratings was quantified by means of weighted kappa (κ).

Ziprasidone in adolescents with schizophrenia: results from a placebo-controlled efficacy and long-term open-extension study.

Objective: The purpose of this study was to evaluate the short- and long-term efficacy, safety, and tolerability of ziprasidone in adolescents with schizophrenia.

Methods: Subjects ages 13-17 years with schizophrenia (American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. [DSM-IV]) were enrolled in a 6 week, randomized, double-blind, placebo-controlled multicenter trial (RCT) followed by a 26 week open-label extension study (OLE).

Efficacy, long-term safety, and tolerability of ziprasidone in children and adolescents with bipolar disorder.

Objective: The purpose of this study was to evaluate the short- and long-term efficacy and safety of ziprasidone in children and adolescents with bipolar I disorder.

Methods: Subjects 10-17 years of age with a manic or mixed episode associated with bipolar I disorder participated in a 4 week, randomized, double-blind, placebo-controlled multicenter trial (RCT) followed by a 26 week open-label extension study (OLE). Subjects were randomized 2:1 to initially receive flexible-dose ziprasidone (40-160 mg/day, based on weight) or placebo.

Meta-regression analysis of placebo response in antipsychotic trials, 1970-2010.

Objective: Large placebo response presents a major challenge for psychopharmacologic drug development and contributes to the increasing failure of psychiatric trials. The objective of this meta-regression analysis was to identify potential contributors to placebo response in randomized controlled trials of antipsychotic treatment in schizophrenia.

Method: The authors extracted trial design and clinical variables from eligible randomized controlled trials (N=50) identified through searches of MEDLINE (1960-2010) and other sources.

Intramuscular ziprasidone versus haloperidol for managing agitation in Chinese patients with schizophrenia.

Intramuscular (IM) antipsychotics are preferred for efficient control of agitation symptoms. Previous studies have demonstrated that IM ziprasidone is efficacious and safe for treatment of agitation in schizophrenia. However, clinicians now recognize that racial differences may contribute to altered therapeutic response and tolerability.

Adjunctive oral ziprasidone in patients with acute mania treated with lithium or divalproex, part 2: influence of protocol-specific eligibility criteria on signal detection.

Objectives: High failure rates of randomized controlled trials (RCTs) are well recognized but poorly understood. We report exploratory analyses from an adjunctive ziprasidone double-blind RCT in adults with bipolar I disorder (reported in part 1 of this article). Data collected by computer interviews and by site-based raters were analyzed to examine the impact of eligibility criteria on signal detection.

Adjunctive oral ziprasidone in patients with acute mania treated with lithium or divalproex, part 1: results of a randomized, double-blind, placebo-controlled trial.

Objective: To assess the efficacy and safety of adjunctive ziprasidone in subjects with acute mania treated with lithium or divalproex, with an inadequate response to the mood stabilizer.

Method: The study enrolled subjects aged 18-65 years who had a primary DSM-IV diagnosis of bipolar I disorder, with the most recent episode manic or mixed, with or without rapid cycling, and a Young Mania Rating Scale (YMRS) score ≥ 18. Subjects were randomized under double-blind conditions to receive ziprasidone, 20 to 40 mg (n = 226) or 60 to 80 mg (n = 232), or placebo (n = 222) twice a day for 3 weeks in addition to their mood stabilizer.

Early prediction of clinical and functional outcome in schizophrenia.

Unlabelled: The objective of this paper was to investigate the prognostic and predictive value of a small panel of independent and clinically important factors based on symptom improvement, baseline cognitive impairment, and weight change during the early treatment phase.

Methods: The study sample was based on a double-blind, 6-month continuation study of ziprasidone and olanzapine (N=94). We developed a parsimonious 6-month GAF prediction function using a logistic regression model, and evaluated its predictive accuracy and performance using bootstrap estimates of c-statistics and error in predicted probability.

Placebo response trajectories in short-term and long-term antipsychotic trials in schizophrenia.

Increasing rates of placebo response have eroded placebo-control group differences in randomized controlled trials, although the reasons for this trend remain unclear. Data were extracted from the placebo arms in two identically designed 6-week studies and one 52-week study in the ziprasidone clinical trial database. The objective of this analysis was to identify distinct patterns of placebo response trajectories that could capture individual variability in the time course of change during a 1-year trial using growth mixture latent class analyses.

Efficacy and safety of adjunctive oral ziprasidone for acute treatment of depression in patients with bipolar I disorder: a randomized, double-blind, placebo-controlled trial.

Objective: To assess efficacy and safety of adjunctive ziprasidone in subjects with bipolar depression treated with lithium, lamotrigine, or valproate.

Method: 298 adult outpatients with bipolar I disorder (DSM-IV criteria) were randomized to receive ziprasidone, 20-80 mg twice a day, or placebo twice a day for 6 weeks plus their preexisting mood stabilizer. The primary efficacy variable was change in Montgomery-Asberg Depression Rating Scale (MADRS) total scores from baseline to 6 weeks.

Sertraline treatment of children and adolescents with posttraumatic stress disorder: a double-blind, placebo-controlled trial.

Objective: The aim of this study was to evaluate the safety and efficacy of sertraline in children and adolescents who met Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria for posttraumatic stress disorder (PTSD).

Method: Children and adolescents (6-17 years old) meeting DSM-IV criteria for PTSD were randomized to 10 weeks of double-blind treatment with sertraline (50-200  mg/day) or placebo. The primary efficacy measure was the University of California, Los Angeles Post-Traumatic Stress Disorder Index for DSM-IV (UCLA PTSD-I).

An open-label pilot study of methylphenidate in the treatment of cocaine dependent patients with adult attention deficit/hyperactivity disorder.

A multi-site, open-label study of methylphenidate for treating patients with comorbid diagnoses of attention deficit/hyperactivity disorder and cocaine dependence was performed. Forty-one participants, who met DSM-IV criteria for adult attention deficit/hyperactivity disorder and cocaine dependence, were enrolled into this ten week outpatient study. The targeted total daily dose of methylphenidate was 60 mg (20 mg TID).