Venlafaxine is a serotonin-noradrenaline reuptake inhibitor (SNRI) that has no affinity for muscarinic, adrenergic or histaminergic receptors. In short-term trials, the adverse effects that occurred more often with venlafaxine than with placebo included nausea, somnolence, dizziness, dry mouth, and sweating. Rapid titration of the dose of venlafaxine to higher levels appeared, not unexpectedly, to be associated with an increased incidence of side effects. Side effects that appeared to be dose related included insomnia, nausea and sexual dysfunction. The incidence of nausea and dizziness was highest during the first 2 or 3 weeks of therapy and decreased rapidly thereafter. Somnolence also decreased over time. At high doses blood pressure increases were reported in a small percent of patients on venlafaxine and antidepressant drugs but were uncommon at the venlafaxine dose of 75–150 mg daily. Studies with venlafaxine in healthy volunteers indicate a low potential for drug-drug interactions. Overdoses have been reported in 14 of 3,082 patients administered venlafaxine in clinical trials, and no deaths were reported among these patients. Overdoses of venlafaxine induced mainly drowsiness and lethargy.

The benefits of an antidepressant with an early or rapid onset of action include a more rapid resolution of the debilitating symptoms of depression, a potential reduction in the risk of suicide and cost savings associated with a reduction in hospitalization. While these benefits are valuable, this promise has yet to be fulfilled by any antidepressant. Venlafaxine is a unique serotonin-noradrenaline reuptake inhibitor (SNRI) which produces rapid and prolonged desensitization of β-adrenergic receptors in preclinical studies after both acute and chronic administration of venlafaxine. Results from placebo-controlled and active comparator clinical studies provide evidence that venlafaxine may have an early onset of activity which is most apparent at higher dosages. The early onset is most apparent with rapid escalation of the venlafaxine dosage, and the incidence, therefore, of side effects tends to be higher early after initiating therapy with venlafaxine. Thus, venlafaxine may fill the long awaited need for an antidepressant with an early onset of action.