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

Venlafaxine inhibits presynaptic reuptake of serotonin (5-hydroxytryptamine ; 5-HT) and noradrenaline (norepinephrine). Venlafaxine extended-release (X R) 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 depressio n was evident at week 2 of treatment with venlafaxine XR 75 to 225 mg/day i n a placebo-controlled trial. By week 4, the drug was significantly more ef fective than placebo at reducing both the Hamilton Rating Scale for Depress ion (HAM-D) and Montgomery-Asberg; Depression Rating Scale (MADRS) total sc ores. Furthermore. cumulative relapse rates were lower among recipients of venlafaxine XR 75 to 225 mg/day than placebo recipients after 3 and 6 month s 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 place bo during a 12-week study. Reductions from baseline in all 4 efficacy param eters (HAM-D. MADRS, HAM-D depressed mood item and the Clinical Global Impr ession Severity of Illness scale) were significantly higher among patients treated with venlafaxine XR than venlafaxine IR or placebo at week 12 (usin g an intent-to-treat. last observation carried forward analysis). Venlafaxine XR 75 to 225 mg/day was compared with fluoxetine 20 to 60 mg/da y in patients with major depression in 2 randomised. double-blind, placebo- controlled, multicentre studies. Remission rates were significantly in favo ur of venlafaxine XR recipients in one study: 37, 22 and 18% of patients tr eated with venlafaxine XR. fluoxetine or placebo, respectively, achieved fu ll remission (HAM-D total score less than or equal to 7 at end-point). In t he other trial. venlafaxine XR and fluoxetine had comparable efficacy in re ducing HAM-D and Hamilton Rating Scale for Anxiety (HAM-A) total scores com pared with placebo. However, the HAM-A response rate was significantly high er with venlafaxine XR than with fluoxetine at week 12. In a comparative study involving paroxetine, reductions from baseline in HA M-D and MADRS total scores in patients given venlafaxine XR 75 mg/day or pa roxetine 20 mg/day for 12 weeks were significant, but no significant differ ences between treatment groups were evident. Discontinuation rates because of unsatisfactory clinical response were simi lar among patients treated with venlafaxine XR, fluoxetine or paroxetine. Adverse events pertaining to the digestive (nausea. dry mouth), nervous (di zziness, somnolence, insomnia) and urogenital (abnormal ejaculation) system s as well as sweating were the most frequently reported adverse events duri ng 8 to 12 weeks of treatment in 3 randomised, double-blind, multicentre tr ials. Comparative studies with fluoxetine and paroxetine demonstrated a sim ilar adverse event profile to venlafaxine XR. Conclusion: Venlafaxine XR has shown efficacy in the treatment of major dep ression and was at least as effective as fluoxetine or paroxetine and more effective than venlafaxine IR. Furthermore, it is effective at reducing sym ptoms of anxiety in depressed patients. The incidence of adverse events in recipients of venlafaxine XR is similar to that in patients receiving treat ment with well established selective serotonin reuptake inhibitors. As an e ffective and well tolerated antidepressant, venlafaxine XR should be consid ered as a first-line pharmacological treatment in patients with major depre ssion.