Venlafaxine: measuring the onset of antidepressant action

Venlafaxine, a new antidepressant, inhibits reuptake of norepinephrine and serotonin without appreciable effects on histaminergic, alpha-adrenergic, or cholinergic systems. Pharmacologically the drug is unique: the half-life is short and it exerts both rapid and prolonged beta-adrenergic desensitization after single doses in a rodent model. Venlafaxine has been thought to possess a rapid onset of clinical antidepressant action. Accordingly, two clinical studies in which moderate amounts of venlafaxine were given aggressively were reviewed to examine aspects of the drug's onset of action. Three statistical methodologies were employed--traditional analysis of depression scale scores, pattern analysis based on timing and persistence of response, and survival analysis of sustained response. All three methods showed venlafaxine to have significant effects early in the course of therapy. In addition, venlafaxine is the first drug to meet criteria for early onset using the pattern analysis methodology. Depressed patients aggressively treated with venlafaxine show significant benefit on or before Day 7 of treatment using traditional methods of analysis as well as survival analysis of sustained response.