Venlafaxine extended-release : A review of its use in the management of major depression

• Published in: CNS drugs 2001, Vol.15 (8), p.643-669
• Main Authors: WELLINGTON, Keri, PERRY, Caroline M
• Format: Article
• Language: English
• Subjects: Antidepressive Agents, Second-Generation - administration & dosage; Anxiety - drug therapy; Biological and medical sciences; Cyclohexanols - administration & dosage; Cyclohexanols - pharmacokinetics; Cyclohexanols - pharmacology; Delayed-Action Preparations; Depressive Disorder, Major - drug therapy; Drug Interactions; Fluoxetine - therapeutic use; Humans; Medical sciences; Neuropharmacology; Paroxetine - therapeutic use; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Serotonin Uptake Inhibitors - administration & dosage; Venlafaxine Hydrochloride
• ISSN: 1172-7047; 1179-1934
• DOI: 10.2165/00023210-200115080-00007

Venlafaxine inhibits presynaptic reuptake of serotonin (5-hydroxytryptamine; 5-HT) and noradrenaline (norepinephrine). Venlafaxine extended-release (XR) has been investigated in patients with major depression and in patients with major depression with associated anxiety in randomised, double-blind, multicentre trials. A therapeutic response in patients with major depression was evident at week 2 of treatment with venlafaxine XR 75 to 225 mg/day in a placebo-controlled trial. By week 4, the drug was significantly more effective than placebo at reducing both the Hamilton Rating Scale for Depression (HAM-D) and Montgomery-Asberg Depression Rating Scale (MADRS) total scores. Furthermore, cumulative relapse rates were lower among recipients of venlafaxine XR 75 to 225 mg/day than placebo recipients after 3 and 6 months in another trial. Venlafaxine XR 75 to 150 mg/day was significantly more effective than venlafaxine immediate-release (IR) 75 to 150 mg/day or placebo during a 12-week study. Reductions from baseline in all 4 efficacy parameters (HAM-D, MADRS, HAM-D depressed mood item and the Clinical Global Impression Severity of Illness scale) were significantly higher among patients treated with venlafaxine XR than venlafaxine IR or placebo at week 12 (using an intent-to-treat, last observation carried forward analysis). Venlafaxine XR 75 to 225 mg/day was compared with fluoxetine 20 to 60 mg/day in patients with major depression in 2 randomised, double-blind, placebo-controlled, multicentre studies. Remission rates were significantly in favour of venlafaxine XR recipients in one study: 37, 22 and 18% of patients treated with venlafaxine XR, fluoxetine or placebo, respectively, achieved full remission (HAM-D total score < or = 7 at end-point). In the other trial, venlafaxine XR and fluoxetine had comparable efficacy in reducing HAM-D and Hamilton Rating Scale for Anxiety (HAM-A) total scores compared with placebo. However, the HAM-A response rate was significantly higher with venlafaxine XR than with fluoxetine at week 12. In a comparative study involving paroxetine, reductions from baseline in HAM-D and MADRS total scores in patients given venlafaxine XR 75 mg/day or paroxetine 20 mg/day for 12 weeks were significant, but no significant differences between treatment groups were evident. Discontinuation rates because of unsatisfactory clinical response were similar among patients treated with venlafaxine XR, fluoxetine or paroxetine. Adverse events pertaining