New Research Session Four: Focus on Ziprasidone

Nearly 90 posters were presented during the fourth New Research Session at the APA Annual Meeting, held from noon-2:00PM on Tuesday, May 25, with many focused on ziprasidone.

A 6-week Randomized Double-blind Placebo-controlled Trial of Ziprasidone for the Acute Depressive Mixed State

Poster Number: NR4-03

Researchers: Ashwin A. Patkar, MD, William Gilmer,MD, Manmohandeep Sohi, MD, Elizabeth Whitham, BA,Sairah Thommi, BS, Anthony Loebel, MD, Prakash Masand,MD, S. Nassir Ghaemi, MD, MPH, Chi-un Pae, MD,PhD

Purpose: To examine “the efficacy of ziprasidone versusplacebo for the depressive mixed state in patients withbipolar II disorder or unipolar depression,” with ziprasidone chosen “due to its biochemical profile which may suggestboth antidepressant as well as antimanic properties.”

Results: Significant reductions were seen in Montgomery-Asberg Depression Rating Scale scores from baseline to treatment end in those treated with ziprasidone, compared with those who received placebo. Further, reduction from baseline in Quick Inventory of Depressive Symptomatology Self Report favored ziprasidone over placebo, and responders on Clinical Global Impression-I Overall were greater in those who received the drug (62%) than those who received placebo (15%). Overall, the agent was well tolerated, with side effects—insomnia, sedation, irritability, dry mouth, and increased appetite—reported by 5% of participants in both groups.

Analysis of the Effect of Ziprasidone on Agitation in Acute Bipolar Mania Using Clinician-rated PANSS and SADS-C Proxy Measures

Poster Number: NR4-12

Researchers: Cedric O'Gorman, MD, Steven Potkin, MD,Francine Mandel, PhD, Douglas Vanderburg, MD

Purpose:O’Gorman explained that this research was conducted “to examine the effect

of ziprasidone on items from the PANSS and the SADS-C, which may most closely approximate objective measures for agitation in acute bipolar mania,” as well as examine “the possible contribution of concomitant benzodiazepines to this effect.”

Results: Reading from his poster, O’Gorman said that “Ziprasidone subjects experienced significant (p < 0.05) reductions versus placebo subjects in several agitation-related items at early time points, including PANSS poor impulse control (days 7 and 14), anxiety (day 7), uncooperative (day 7), and hostility (day 7); as well as SADS-C insomnia (days 2, 4, and 7), initial insomnia (day 4), middle insomnia (days 4, 7), subjective anger (days 4, 7, 14), and agitation (day 2). The use of benzodiazepines was similar between ziprasidone and placebo subjects (46.2% vs 50.0%, respectively).” With these findings, the presenter’s team concluded that “the fact that rates of benzodiazepine use were similar between ziprasidone and placebo subjects suggests that the observed reduction in agitation was due to ziprasidone alone.”

Treatment Outcomes Based on Disease Severity for Subjects with Bipolar I Disorder Treated with Ziprasidone Plus a Mood Stabilizer

Poster Number: NR4-13

Researchers: Charles Bowden, MD, Balarama Gundapaneni, MS, Cedric O’Gorman, MD, Elizabeth Pappadopulos, PhD, Jeffrey Schwartz, PhD, Rodger Kobes, MD, Onur Karayal, MD

Purpose: To compare the proportion of subjects—in a “6-month, randomized, placebo-controlled, double-blind trial enrolling subjects with bipolar I disorder and a Mania Rating Scale (MRS) score = 14,” in which “ziprasidone was found to be an effective and well-tolerated treatment in combination with a mood stabilizer”&mdash;who were randomized to doubleblind treatment and with those who relapsed during double-blind treatment for the most severely ill quartile and decile.

Results: Bowden’s team found that when added to valproate or lithium, ziprasidone was as effective at stabilizing patients who were mild-to-moderately ill as it was in stabilizing those who were severely ill. Further, mild-to-moderately ill participants who were “randomized to continue on ziprasidone were significantly less likely to relapse compared with placebo subjects.”

Effects on Cognition of Adjunctive Ziprasidone versus Placebo in a Long Term, randomized, Double Blind Trial in Subjects with Bipolar Disorder

Poster Number: NR4-27

Researchers: Elizabeth Pappadopulos, PhD, Richard Keefe, MD, Onur Karayal, MD, Francine Mandel, PhD, Doug Vanderburg, MD, Sonya Lewis, PhD, Michelle Stewart, PhD

Purpose: The aim of this study, explained Pappadopulos was to “discuss the impact ofziprasidone when added to lithium or valproate on cognitiveperformance in maintenance treatment of bipolar disorder.”

Results: “Long-term treatment with ziprasidone plus either lithium or valproate had no greater impact on cognitive function than treatment with either mood stabilizer alone,” said Pappadopulos, summarizing her team’s findings.

Anxiety as a Predictor or Moderator for Effect of Ziprasidone Combined with Mood Stabilizer in Maintenance Treatment of Bipolar I Disorder

Poster Number: NR4-82

Researchers: Terence A. Ketter, MD, Douglas Vanderburg, MD, MPH, Cynthia O. Siu, PhD, Elizabeth A Pappadopulos, PhD, Onur Karayal, MD, MPH

Purpose: “To investigateanxiety as a predictor or moderator of the therapeutic effectsof ziprasidone combined with a mood stabilizer (lithium orvalproic acid).

Results: “Ziprasidone combined with mood stabilizers is more effective than mood stabilizer alone in preventing interventions for mood episode, in both high and low baseline anxiety levels,” explained Ketter. “Our findings suggest that baseline comorbid anxiety can have predictive or moderating influence on the efficacy of adjunctive ziprasidone treatment for bipolar disorder.”