Thioridazine dose-related effects on biomechanical force platform measures of sway in young and old men

OBJECTIVE: Thioridazine (TDZ) is associated with an increased risk of falls. The purpose of this study was to determine whether (1) thioridazine increases Biomechanics Force Platform (BFP) measures of sway in a dose- related manner, (2) there is a difference in sway between young and old men, (3) there is a correlation between sway and orthostatic changes in BP and HR. DESIGN: Seven younger (aged 20-42) and five older (aged 70-76) healthy male volunteers received, in a randomized order double-blind design, a single oral dose of 0, 25, and 50 mg of TDZ on three separate days at least 7 days apart and 75 mg on the fourth day of the study. Sway and blood pressure were measured for 24 hours. SETTING: A general clinical research center. MEASUREMENTS: Biomechanics force platform measures of postural sway were measured as the movement of the center of pressure. The elliptical area (EA) and average velocity (AV) were calculated with eyes open and eyes closed. Blood pressure and heart rate were measured for 5 minutes supine and 5 minutes standing. RESULTS: Thioridazine increases BFP sway in a dosedependent manner. EA increased from 0.56 (SD = .51) cm² for placebo to 0.88 (SD = 1.09) cm² for 75 mg TDZ. AV increased from 1.07 (SD = .27) cm/sec, placebo, to 1.43 (SD = .55) cm/sec, 75 mg TDZ. Older men swayed more than younger men. Changes followed the expected time course for TDZ. EA and AV were associated with HR and BP, e.g., SBP versus ln(EA) and ln(AV) (r = -0.21 and r = -0.22, respectively; P < .0001). CONCLUSIONS: Thioridazine increases validated measures of fall risk dose dependently in young and old men. This may explain the effects of neuroleptic drugs on fall risk in older people.