Objective: Nearly 50% of patients with schizophrenia hav ecomorbid anxiety disorders. Ziprasidone's unique pharmacological profile, including 5-HT1A agaonism and 5-HT and NE reuptake inhibition, may confer anxiolytic properties. And exploratory analysis was conducted to evaluate improvement in anxiety in stable schizophrenic outpatients, as standard scales assessing psychosis do not adequately address anxity. Stable outpatients were selected to reduce the influence of acute psychosis.

Methods: Patients on conventional antipsychotics (n=93), olanzapine (n=88), and risperidone (n=41) were randomized to one of three dosing schedules and received ziprasidone 40–160 mg/day in three 6-week, open-label trials. Anxiety was measured by the PANSS anxiety item (G2: 1, absent, to 7, extreme). Analysis of patients with moderate or greater anxiety (≥4), as well as analysis of those with at least minimal anxiety (≥2), was conducted. Other symptom items were analyzed to address the speccificity of potential treatment differences.

Results: In patients with moderate or greater baseline anxiety, significant improvement in the PANSS anxiety time was observed (P<0.05). Significant improvement was also seen in the group of patients with at least minimal baseline anxiety (P<0.05). There were no concomitant signigicant changes in depression or somatic concern in the moderate anxiety subsample.

Conclusions: Improvement in the PANSS anxiety item, separate from changes in depression and somatic concern, was observed. In view of the prevalence of anxiety symptoms in schizophrenia, controlled trials utilizing anxiety scales validated in this population are necessary to further evaluate ziprasidone's anxwlytk potential.