| Abstrakt: |
The aim of this study was to make a preliminary investigation of the efficacy and safety of zatosetron maleate, a selective 5-hydroxytryptamine-3 receptor antagonist for patients with a broad range of anxiety symptoms. A double-blind, parallel, placebo-controlled pilot study was conducted in 43 patients, aged 18 to 65 years, scoring >17 on the Hamilton Rating Scale for Anxiety (HAM-A). Patients were randomly assigned to either a fixed oral dose of 0.2, 1, or 5 mg of zatosetron or placebo for 4 weeks, followed by a 2-week placebo phase. Enhanced blinding procedures reduced the influence of side effects on efficacy ratings and obscured phases of the research design to patient and clinician. A change in HAM-A scores from baseline to endpoint was the principal efficacy measure; HAM-A Psychic and Somatic subscales, the Symptom Checklist-90, Montgomery-Asberg Depression Rating Scale, and Clinical Global Impressions Scale subscales provided secondary change indices. Adverse events (AEs) (spontaneously mentioned and elicited with the Udvalg for Kliniske Undersøgelser side effect rating scale), vital signs, electrocardiographic findings, and laboratory analytes were compared among treatment groups. Eighty-eight percent of the patients met the criteria for generalized anxiety disorder. No statistically significant differences in outcome measures differentiated among the four treatment groups. However, a pattern of greater change in the HAM-A scores seemed to favor zatosetron over placebo. Placebo was associated with only modest HAM-A score changes and a 30% response rate. The greatest numeric decrease in the HAM-A score and the highest response rate (45%) occurred in the groups receiving 0.2 and 1 mg of zatosetron. The secondary measures of efficacy demonstrated similar outcomes. There were no deaths or serious AEs reported in this study. This pilot study demonstrated that zatosetron at doses of 0.2 to 5 mg/day was safe. Although statistical significance was not achieved, the results show a greater numeric trend toward reducing anxiety with zatosetron than with placebo. |
