VENLAFAXINE - A STRUCTURALLY UNIQUE AND NOVEL ANTIDEPRESSANT

OBJECTIVE: To introduce the new antidepressant venlafaxine. Basic phar macokinetic data and clinical trials are reviewed, as well as adverse reactions, drug interactions, dosing guidelines, and therapeutic consi derations. The article also discusses several pharmacotherapy issues a nd 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 cli nical trials that were available prior to submission for publication w ere reviewed. Preliminary trials and unpublished reports were not revi ewed. DATA SYNTHESIS: Venlafaxine hydrochloride is a structurally nove l agent that has recently been approved in the US for the treatment of depression. This unique antidepressant blocks neuronal reuptake of no repinephrine, serotonin, and, to a lesser extent, dopamine. Venlafaxin e and its major active metabolite, O-desmethylvenlafaxine, exhibit lin ear kinetics with an elimination half-life of 5 and 11 hours, respecti vely. Venlafaxine has been evaluated in 7 clinical trials for the trea tment of depression. These have consisted of 2 open trials, 3 double-b lind, placebo-controlled trials, and 2 double-blind trials where venla faxine was compared with trazodone and imipramine. All 7 trials have e stablished efficacy for venlafaxine using standard psychiatric rating scales to measure change of depressive symptoms. The usual daily dosag e ranges from 75 to 225 mg/d in 2 to 3 divided doses, with a maximum d aily dosage of 375 mg/d. The drug's adverse effect profile differs som ewhat from other more specific serotonin reuptake inhibitors in that i t appears to cause dry mouth, somnolence, and elevated blood pressure as well as nausea, headache, and dizziness. CONCLUSIONS: Although venl afaxine has recently become available for use as an antidepressant in the US, few clinical trials have been [GRAPHICS] 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 new est comparative standard. The clinical place for venlafaxine in the tr eatment of depression has yet to be determined.