VENLAFAXINE - A HETEROCYCLIC ANTIDEPRESSANT

The pharmacology, pharmacokinetics, and clinical efficacy of venlafaxi ne hydrochloride, a new antidepressant, are described. Venlafaxine inh ibits the re-uptake of serotonin, norepinephrine, and, to a lesser ext ent, dopamine. In animal models, it does not significantly inhibit mus carinic, histaminic, or adrenergic receptor activity and does not inhi bit monoamine oxidase. Venlafaxine is rapidly absorbed and metabolized in the liver to its active metabolite, O-desmethylvenlafaxine (ODV). Time to peak concentration is one to two hours for the parent compound and four to five hours for ODV. The pharmacokinetics of venlafaxine m ight be dose-dependent, although pharmacokinetic studies have had conf licting results. The major route of elimination is renal; thus, patien ts with renal dysfunction may require lower doses. In double-blind, pl acebo-controlled trials of venlafaxine for maintenance therapy, venlaf axine has shown effective antidepressant activity in severely ill pati ents with major depression. Antidepressant effectiveness may be appare nt within two weeks; this finding needs to be replicated. The dosage i s 75-375 mg/day administered in two or three divided doses. The streng th of the antidepressant response may be correlated with increasing do sage. Nausea is the most commonly reported adverse drug reaction (ADR) . Others include somnolence, dizziness, dry mouth, and sweating. All A DRs have commonly occurred at the beginning of therapy and decreased w ith time. Overall, venlafaxine is well tolerated. Venlafaxine is as ef fective as other available antidepressants. It may cause fewer anticho linergic, antihistaminic, and antiadrenergic ADRs and may have a quick er onset of therapeutic action than existing antidepressants.