Venlafaxine (Effexor, Efexor) is an antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class first introduced by Wyeth in 1993. It is prescribed for the treatment of major depression and anxiety disorders, among other uses. Due to the pronounced side effects and suspicions that venlafaxine may significantly increase the risk of suicide, it is not recommended as a first line treatment of depression. However, it is often effective for depression not responding to SSRIs. Venlafaxine was the sixth most widely-used antidepressant based on the number of retail prescriptions in the US (17.1 million) in 2006.

Approved

Venlafaxine is used primarily for the treatment of major depression, generalized anxiety disorder, social anxiety disorder, and panic disorder in adults.

Depression

Venlafaxine was shown to be effective for depression in multiple double blind studies. Venlafaxine is similar in efficacy to the tricyclic antidepressants amitriptyline (Elavil) and imipramine and it was better tolerated than amitriptyline. Venlafaxine appears to have efficacy similar or somewhat better than sertraline (Zoloft) and fluoxetine (Prozac) depending on the criteria and rating scales used. In particular, higher doses of venlafaxine are more effective, and more patients achieved remission or were "very much improved". At the same time the efficacy was similar if the number of patients who achieved "response" or were "improved" was considered. A meta-analysis comparing venlafaxine and combined groups of SSRI or tricyclic antidepressants indicated superiority of venlafaxine. Based on the same set of criteria, venlafaxine was similar in efficacy to an atypical antidepressant bupropion (Wellbutrin); however, the remission rate was significantly lower for venlafaxine. Venlafaxine was also marginally inferior in efficacy to a newer SSRI escitalopram (Lexapro) and had twice higher frequency of the side effects, in particular, nausea, ejaculation disorder, somnolence and sweating. In a double-blind study, patients who did not respond to an SSRI were switched to venlafaxine or citalopram. Similar improvement was observed in both groups.

A popular magazine Consumer Reports, which in 2004 had rated venlafaxine as the most effective among six commonly prescribed antidepressants, no longer recommends it. Fluoxetine, citalopram and bupropion have been chosen as Consumer Reports Best Buy drugs in the updated version of their guide, based upon effectiveness, safety, side effects, and cost.

Off-label / investigational uses

Many doctors are starting to prescribe venlafaxine "off label" for the treatment of diabetic neuropathy (in a similar manner to duloxetine) and migraine prophylaxis (in some people, however, venlafaxine can exacerbate or cause migraines). Studies have shown venlafaxine's effectiveness for these conditions. It has also been found to reduce the severity of 'hot-flashes' in menopausal women.