title: Once- versus twice-daily venlafaxine therapy in major depression: a randomized, double-blind study.
abstract: BACKGROUND
  Psychotropic drug dosing regimens are often based on the pharmacokinetic elimination half-life of the compound. This implies that the pharmacokinetic half-life of the drug may be the critical or sole determinant of pharmacodynamic half-life. In the present study, we examined the safety and efficacy of once- versus twice-daily dosing regimens of the immediate-release formulation of venlafaxine, a serotonin and norepinephrine reuptake site blocker with a short elimination half-life.
  
  
  METHODS
  Forty-eight patients with a diagnosis of DSM-IV major depressive episode were randomly assigned to once-daily (N = 25) versus twice-daily (N = 23) venlafaxine. Venlafaxine was started at 37.5 mg daily with specified increments up to 225 mg daily. Efficacy was rated using the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Clinical Global Impressions scale (CGI).
  
  
  RESULTS
  Twenty-one patients in each group completed 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 groups (p < .001). There were no statistically significant differences in 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 score 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.
  
  
  CONCLUSIONS
  These results indicate that the immediate-release formulation of venlafaxine may be safe and effective in some patients when used in a once-daily dose regimen. Moreover, the present results suggest that the short elimination half-life of immediate-release venlafaxine should not be the sole determinant for multiple daily dosing and that antidepressant activity may be more profoundly influenced by a drug's pharmacodynamic half-life than by its pharmacokinetic half-life.
authors.affiliation: Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Amsterdam
authors.forename: M B
authors.initials: MB
authors.lastname: Hooper
authors.forename: J
authors.initials: J
authors.lastname: Amchin
mesh_terms: D000328:Adult; D000553:Ambulatory Care; D003511:Cyclohexanols / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006207:Half-Life; D006801:Humans; D016014:Linear Models; D008297:Male; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride
chemical_list: D003511:Cyclohexanols; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride