Adjunctive therapy with pregabalin in generalized anxiety disorder patients with partial response to SSRI or SNRI treatment.

This study evaluated the efficacy of adjunctive pregabalin versus placebo for treatment of patients with generalized anxiety disorder (GAD) who had not optimally responded to previous or prospective monotherapies. This was a phase 3, randomized, double-blind, placebo-controlled study. Patients diagnosed with GAD who had a historical and current lack of response to pharmacotherapy [Hamilton Anxiety Rating Scale (HAM-A) of ≥ 22 at screening] were randomized to adjunctive treatment with either pregabalin (150-600 mg/day) or placebo.

Effects of high-dose ziprasidone and haloperidol on the QTc interval after intramuscular administration: a randomized, single-blind, parallel-group study in patients with schizophrenia or schizoaffective disorder.

Background: Antipsychotic agents have been associated with a prolonged QT interval. Data on the effects of ziprasidone and haloperidol on the QTc interval are lacking.

Objective: This study aimed to characterize the effects of 2 high-dose intramuscular injections of ziprasidone and haloperidol on the QTc interval at T(max).

Effects of Oral Ziprasidone and Oral Haloperidol on QTc interval in patients with Schizophrenia or Schizoaffective disorder.

Study Objective: To characterize the effect of oral ziprasidone and haloperidol on the corrected QT (QTc) interval under steady-state conditions. Design. Prospective, randomized, open-label, parallel-group study.

The effect of food on the absorption of oral ziprasidone.

Oral ziprasidone bioavailability is increased when taken with food. Here we describe two pharmacokinetic studies to quantify the impact of food on ziprasidone absorption in healthy volunteers. The first, an open-label, six-way crossover study, investigated ziprasidone absorption in eight healthy men.

Single-dose pharmacokinetics and safety of ziprasidone in children and adolescents.

Objective: The purpose of this study was to provide single-dose pharmacokinetic, safety, and tolerability data for ziprasidone in youths with tic disorder, for comparison to adult studies to discern whether ziprasidone pediatric dosing could be modeled from adult data.

Method: A single-dose, open-label study of ziprasidone was conducted in youths (ages 7-16 years) with Tourette's disorder or chronic tic disorder. Dosing of ziprasidone oral suspension (40 mg/mL) was weight adjusted: >60 kg, 20 mg (group 1, n = 8); 31 to 60 kg, 10 mg (group 2, n = 8); and 16 to 30 kg, 5 mg (group 3, n = 8).

Pharmacokinetics, safety, and tolerability of intramuscular ziprasidone in healthy volunteers.

Little has been published regarding the pharmacokinetics of the intramuscular (IM) formulation of Ziprasidone. The authors report results from 2 early phase I studies in healthy volunteers: a trial of single 5-, 10-, or 20-mg IM doses of ziprasidone in 24 subjects and an open-label 3-way crossover trial of 5-mg intravenous (IV), 5-mg IM, and 20-mg oral ziprasidone in 12 subjects. Absorption of IM ziprasidone was rapid (Tmax < 1 hour).

A randomized evaluation of the effects of six antipsychotic agents on QTc, in the absence and presence of metabolic inhibition.

Many drugs have been associated with QTc prolongation and, in some cases, this is augmented by concomitant administration with metabolic inhibitors. The effects of 6 antipsychotics on the QTc interval at and around the time of estimated peak plasma/serum concentrations in the absence and presence of metabolic inhibition were characterized in a prospective, randomized study in which patients with psychotic disorders reached steady-state on either haloperidol 15 mg/d (n = 27), thioridazine 300 mg/d (n = 30), ziprasidone 160 mg/d (n = 31), quetiapine 750 mg/d (n = 27), olanzapine 20 mg/d (n = 24), or risperidone 6-8 mg/d increased to 16 mg/d (n = 25/20). Electrocardiograms (ECGs) were done at estimated Cmax at steady-state on both antipsychotic monotherapy and after concomitant administration of appropriate cytochrome P-450 (CYP450) inhibitor(s).

Pharmacodynamics of ziprasidone in children and adolescents: impact on dopamine transmission.

Objective: Ziprasidone is an atypical antipsychotic with a high ratio of 5-HT(2A) to D(2) receptor antagonism. It is also an agonist at 5-HT(1A), which has been shown in rats to increase dopamine in prefrontal cortex. The objective of this study was to probe the dopamine agonist and antagonist pharmacodynamic properties of ziprasidone in youth.

Ziprasidone metabolism, aldehyde oxidase, and clinical implications.

Ziprasidone (Geodon, Zeldox), a recently approved atypical antipsychotic agent for the treatment of schizophrenia, undergoes extensive metabolism in humans with very little (<5%) of the dose excreted as unchanged drug. Two enzyme systems have been implicated in ziprasidone metabolism: the cytosolic enzyme, aldehyde oxidase, catalyzes the predominant reductive pathway, and cytochrome P4503A4 (CYP3A4) is responsible for two alternative oxidation pathways. The involvement of two competing pathways in ziprasidone metabolism greatly reduces the potential for pharmacokinetic interactions between ziprasidone and other drugs.

The anxiolytic effect of the novel antipsychotic ziprasidone compared with diazepam in subjects anxious before dental surgery.

The novel atypical antipsychotic ziprasidone has a pharmacologic profile notable for potent agonism of serotonin (5-HT)1A receptors, antagonism at 5-HT1D receptors, and reuptake inhibition of norepinephrine. 5-HT1A receptor agonism, in particular, suggests anxiolytic activity, and ziprasidone has shown preliminary efficacy in treating the symptoms of anxiety associated with psychotic disorders. In this study, the anxiolytic efficacy of ziprasidone was evaluated in nonpsychotic subjects who were anxious before undergoing minor dental surgery.