Ziprasidone Treatment of Refractory Generalized Anxiety Disorder

Abstract

This 8-week, randomized, double-blind, placebo-controlled, flexible-dose trial assessed the efficacy, safety, and tolerability of ziprasidone in adults with treatment-resistant generalized anxiety disorder (GAD). Seventy-three subjects with treatment-resistant GAD were recruited, and 62 were randomized to either ziprasidone or placebo treatment at a ratio of 2:1 using a flexible dosing strategy (20-80 mg daily). Randomization was stratified into 2 subtypes of patients, those in whom the study drug was used as augmentation and those who have stopped their ineffective medications before entering the present trial (nonaugmented group). The subjects' clinical status was monitored weekly throughout the course of the study and included the Hamilton Anxiety Scale (primary outcome measure), the Clinical Global Impression Improvement and Severity of Illness scales, the Hamilton Depression Scale, the Sheehan Disability Scale, the Hospital Anxiety and Depression Scale, and the Abnormal Involuntary Movements Scale. Sixty-two patients were randomized to ziprasidone (n = 41) or placebo (n = 21). The dropout rate was 24%, consisting of 2 placebo patients and 13 ziprasidone patients. There was no statistically significant difference in the Hamilton Anxiety Scale score reduction between the drug and placebo groups. However, statistical trends were observed for an augmentation-study medication interaction effect, with ziprasidone patients producing more improvement in the nonaugmented than in the augmented group. This study provides pilot data for an augmentation-study medication interaction effect with ziprasidone patients producing more improvement in the nonaugmented than in the augmented group. Based on the data obtained in this trial and the subsequent power analyses, a future double-blind placebo-controlled trial should include at least 150 treatment-resistant GAD nonaugmented patients randomized to ziprasidone and placebo in a 1:1 ratio.

Ziprasidone as Adjunctive Therapy in Severe Bipolar Patients Treated with Clozapine

“…This may suggest caution or a different dosage titration of ziprasidone in subjects with anxiety symptoms, slightly in contrast with prior open-label and placebo-controlled evidences of ziprasidone efficacy in refractory generalized anxiety disorder (GAD) [64, 65]. However, in the double-blind controlled study on GAD, ziprasidone was prescribed to lower flexible doses (i.e., 20–80 mg versus 80–160 daily in our report).…”

Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders

“…Not recommended adjunctive therapies: Ziprasidone does not appear to be effective as adjunctive therapy (Level 2, negative) [611]. …”

Pregabalin for the treatment of generalized anxiety disorder: an update

“…The findings of small randomized placebo-controlled augmentation studies suggest that augmentation of antidepressants with antipsychotic drugs (olanzapine, quetiapine, and risperidone) may be beneficial,74–76 though the evidence for quetiapine augmentation is inconsistent77 and uncertain for ziprasidone augmentation 78. However, the findings of a recent large randomized placebo-controlled augmentation study demonstrate that the addition of pregabalin to SSRI or SNRI antidepressant drugs is superior to continued treatment with antidepressants alone 71…”