ONCE-VERSUS TWICE-DAILY VENLAFAXINE THERAPY IN MAJOR DEPRESSION - A RANDOMIZED, DOUBLE-BLIND-STUDY

Background: Psychotropic drug dosing regimens are often based on the p harmacokinetic elimination half-life of the compound. This im plies th at the pharmacokinetic half-life of the drug may be the critical or so le determinant of pharmacodynamic half-life. In the present study, we examined the safety and efficacy of once-versus twice-daily dosing reg imens of the immediate-release formulation of venlafaxine, a serotonin and norepinephrine reuptake site blocker with a short elimination hal f-life, Method: Forty-eight patients with a diagnosis of DSM-TV major depressive episode were randomly assigned to once-daily (N = 25) versu s twice-daily (N = 23) venlafaxine. Venlafaxine was started at 37.5 mg daily with specified increments up to 225 mg daily. Efficacy was rate d using the Hamilton Rating Scale for Depression (HAM-D), the Montgome ry-Asberg Depression Rating Scale (MADRS), and the Clinical Global Imp ressions scale (CGI). Results: Twenty-one patients in each group compl eted 6 weeks of treatment. We observed a significant reduction in mean weekly HAM-D and MADRS scores at weeks 1 through 6 for both dosing gr oups (p < .001). There were no statistically significant differences i n mean HAM-D or MADRS scores between dosing groups at any time point. There was, however, a nonsignificant trend for a more rapid reduction in the mean HAM-D score at week 2 (p < .06) and in the mean MADRS scor e at week 1 (p < .07) and week 2 (p < .09) in the b.i.d. dosing group. Similarly, there was a significant decrease in the CGI score at week 2 (p < .02) in the b.i.d, dosing group. The rate of adverse events was similar between treatment groups; the most common adverse events were transient nausea and headaches.Conclusion: These results indicate tha t the immediate-release formulation of venlafaxine may be safe and eff ective in some patients when used in a once-daily dose regimen. Moreov er, the present results suggest that the short elimination half-life o f immediate-release venlafaxine should not be the sole determinant for multiple daily dosing and that antidepressant activity may be more pr ofoundly influenced by a drug's pharmacodynamic half-life than by its pharmacokinetic half-life.