Objective: Comprehensive reviews of venlafaxine have been published elsewhere; thus, this update focuses on newer issues of treatment remission in depression, treatment-resistant depression, and extended-release venlafaxine for generalized anxiety disorder (GAD).

Methods: Relevant clinical literature from 1993 through 2003 was identified from database searches of MEDLINE and International Pharmaceutical Abstracts, and from manual searches of reference lists of the identified papers. Search terms included venlafaxine extended-release, venlafaxine XR, treatment-resistant depression, depressive disorders, anxiety disorders, generalized anxiety disorder, and antidepressive agents second generation.

Results: With its dual action of serotonin and noradrenergic reuptake inhibition, venlafaxine has been shown to be superior in efficacy to selective serotonin reuptake inhibitors for severe major depressive disorder, treatment-resistant depression, and depressive symptom remission. Its demonstrated efficacy for both short- and long-term treatment of GAD has led to its use for obsessive-compulsive disorder and chronic pain syndromes, although inadequate clinical literature currently exists to support these latter 2 uses. In the past decade, no new or unexpected adverse events have been identified with venlafaxine therapy, except a possibly greater risk of fatal overdose compared with other serotonergic drugs, suggesting the need for caution in patients with suicidal ideation. Because venlafaxine is a potent serotonin agonist, caution must also be exercised to prevent the possibility of serotonin syndrome when used with other serotonin agonists, and its dose should be tapered very gradually to minimize the risk of a serotonin withdrawal reaction.

Conclusion: Venlafaxine has emerged as a successful post-SSRI-era antidepressant with an expanded range of uses since it was first marketed.