Venlafaxine is a unique antidepressant and first of a novel class of antidepressants – the serotonin-norepinephrine reuptake inhibitors.

Venlafaxine is an attractive alternative to the currently available antidepressants, as a first-line antidepressant for the treatment of patients with major depression and adds a new dimension in the treatment of refractory major depression and generalised anxiety disorders.

Norepinephrine and serotonin reuptake play an important role in the development of depression.

What is unique about venlafaxine, the prototype agent of this group of SNRIs, is that it shares the NE and 5-HT (and to a lesser extent DA) reuptake inhibitory properties of the classical TCAs, but without a, cholinergic, or histamine receptor blocking properties.

Most antidepressants do not become effective for at least 2 weeks after initiation of therapy: treatment is considered to have failed if no response occurs by 4 to 6 weeks.

The preclinical profile of venlafaxine suggests that this agent offers an early onset of efficacy. In addition, clinical studies have demonstrated a rapid onset of action associated with venlafaxine, with antidepressant efficacy as early as week 1 of treatment (and at day 4 in one patient study).

In contrast to the flat dose response curve of the SSRIs, venlafaxine has shown increased response to increased doses in placebo controlled trials evaluating daily doses from 25 mg to 250 mg (Fig. 1).

The available published clinical data show that venlafaxine is significantly more effective than placebo and as effective as the TCAs and SSRIs. Comparative study versus fluoxetine exhibited comparable efficacy and tolerability in major depression. However, among patients requiring higher doses, a better response to venlafaxine was observed with higher doses of venlafaxine.

Several studies suggest that venlafaxine is effective in anxiety disorders including generalised anxiety disorder (GAD), panic disorder, social phobia and obsessive-compulsive disorder (OCD). The effects of venlafaxine in patients with generalised anxiety disorder are independent of its antidepressant activity and represent a pure ‘anxiolytic’ effect.

Venlafaxine is initiated at 75 mg per day in two divided doses (or single dose of the sustained release formulation). Dose increase is carried out at an interval of not less than 4 days and the increments are not more than 75 mg/d.

Maximum recommended dose with plain venlafaxine is 375 mg/d (in 2 or 3 divided doses) and with extended release is 225 mg/day.

The most common adverse events reported with venlafaxine therapy include somnolence, dry mouth, elevated blood pressure, nausea, headache and dizziness. Venlafaxine has a low potential to cause orthostatic hypotension or cardiac conduction disturbance.