Venlafaxine: A Structurally Unique and Novel Antidepressant

Abstract

Objective: To introduce the new antidepressant venlafaxine. Basic pharmacokinetic data and clinical trials are reviewed, as well as adverse reactions, drug interactions, dosing guidelines, and therapeutic considerations. The article also discusses several pharmacotherapy issues and how venlafaxine compares with other available antidepressants. Data Sources: A MEDLINE search was used to identify pertinent literature, including reviews. Study Selection: As this is a relatively new agent, all available clinical trials were reviewed. Data Extraction: All clinical trials that were available prior to submission for publication were reviewed. Preliminary trials and unpublished reports were not reviewed. Data Synthesis: Venlafaxine hydrochloride is a structurally novel agent that has recently been approved in the US for the treatment of depression. This unique antidepressant blocks neuronal reuptake of norepinephrine, serotonin, and, to a lesser extent, dopamine. Venlafaxine and its major active metabolite, O—desmethylvenlafaxine, exhibit linear kinetics with an elimination half-life of 5 and 11 hours, respectively. Venlafaxine has been evaluated in 7 clinical trials for the treatment of depression. These have consisted of 2 open trials, 3 double-blind, placebo-controlled trials, and 2 double-blind trials where venlafaxine was compared with trazodone and imipramine. All 7 trials have established efficacy for venlafaxine using standard psychiatric rating scales to measure change of depressive symptoms. The usual daily dosage ranges from 75 to 225 mg/d in 2 to 3 divided doses, with a maximum daily dosage of 375 mg/d. The drug's adverse effect profile differs somewhat from other more specific serotonin reuptake inhibitors in that it appears to cause dry mouth, somnolence, and elevated blood pressure as well as nausea, headache, and dizziness. Conclusions: Although venlafaxine has recently become available for use as an antidepressant in the US, few clinical trials have been conducted to help the practitioner evaluate its place in the treatment of depression. There are no comparative trials of venlafaxine with the serotonin specific reuptake inhibitor antidepressants, which are rapidly becoming the newest comparative standard. The clinical place for venlafaxine in the treatment of depression has yet to be determined.