The Safety and Tolerability of Venlafaxine Hydrochloride: Analysis of the Clinical Trials Database

Abstract

The tolerability and safety of venlafaxine hydrochloride, a new serotonin and norepinephrine reuptake inhibitor, are reviewed in this article. The data presented here are based on a pool of 3,082 patients who were treated with this agent during clinical trials. Of these patients, 2,897 received venlafaxine for depression; 455 of these patients were treated for more than 360 days. The tolerability and safety profiles of venlafaxine were similar to those previously reported for selective serotonin reuptake inhibitors. Patients receiving venlafaxine experienced nausea, insomnia, dizziness, somnolence, constipation, and sweating more often than did patients receiving placebo but reported anticholinergic events less frequently than did patients receiving tricyclics. This is accounted for by the fact that, unlike the tricyclics, venlafaxine lacks significant affinity for muscarinic cholinergic receptors. Resolution of venlafaxine-associated nausea occurred rapidly in the vast majority of the patients who reported it at the start of therapy. Serious adverse events were rare among venlafaxine-treated patients. A small percentage of the patients given venlafaxine experienced modest but significant increases in blood-pressure readings, similar to those observed among imipramine-treated patients. At mean daily venlafaxine dosages of up to 300 mg, the percentage of venlafaxine-treated patients who had sustained elevations in supine diastolic blood pressure during treatment ranged from 2% to 6%, compared with 2% and 5% among the placebo- and imipramine-treated patients, respectively. All of the 14 patients who took an overdose of venlafaxine recovered without sequelae. Tolerability and safety in the elderly did not differ significantly from that observed in younger patients.

Neuropharmacology of venlafaxine

“…For patients receiving daily doses of venlafaxine below 100 mg for 6 weeks, the chance of having a sustained increase in blood pressure was no greater than placebo. For patients receiving higher daily doses of venlafaxine up to 300 mg, the chance of having a sustained blood pressure elevation was 3 to 4% higher than that of placebo-treated patients, and for patients receiving >300 mg the chance was 11% higher than that of placebo-treated patients [Rudolph and Derivan, 1996]. For half of the venlafaxine-treated patients that had sustained blood pressure increases, their blood pressure readings declined below the definition for sustained blood pressure elevation during continued venlafaxine treatment.…”

A Comparison of Venlafaxine and SSRIs in Deliberate Self-poisoning

“…In the early days of its clinical use venlafaxine was thought to have a toxicity profile similar to that reported for selective serotonin reuptake inhibitors (SSRIs) and was sometimes grouped with the SSRIs in self-poisoning studies [1,2].…”

Anticholinergic-type effects following a pediatric venlafaxine overdose

“…As doses increase, they begin to exert their actions at norepinephrine receptors, until high doses are reached at which time they begin to show some dopamine receptor affinity (1,2). Neither venlafaxine nor ODV have shown a high affinity for muscarinic receptors, meaning that the medication should have a lower incidence of anticholinergic effects when compared to other antidepressants (3,4).…”