When selecting an
antidepressant, a number of factors must be considered. These considerations are summarized under the mnemonic STEPS: Safety, Tolerability, Efficacy, Payment (eg, cost-effectiveness), and Simplicity of use.
Venlafaxine is the first of a new class of
antidepressants that selectively blocks the
serotonin and
noradrenaline uptake pumps without blocking
muscarinic, histaminergic and
adrenergic receptors or inhibiting
sodium fast channels. Because
venlafaxine avoids these mechanisms of action, it has a wide therapeutic index, an improved tolerability profile and a reduced risk of causing pharmacodynamically mediated
drug-drug interactions when compared to
tricyclic antidepressants (TCAs). In contrast to some other new
antidepressants,
venlafaxine also avoids effects on
cytochrome P450 which are likely to cause clinically meaningful, pharmacokinetically mediated
drug-drug interactions. The effects on the uptake pumps of both
serotonin and
noradrenaline appear to be responsible for some of
venlafaxine's unique features in terms of
antidepressant efficacy, including its ascending
antidepressant dose-response curve and its apparent rapid onset of
antidepressant action at the upper end of its clinically relevant dosing range.
Venlafaxine is effective in a broad spectrum of patients, including outpatients and inpatients, those with and without
melancholia, patients with symptoms of anxiety or agitation or retardation and patients with first time or recurrent episodes of major depression. An important factor when selecting an
antidepressant is the simplicity of the dosing regimen and the ability to rapidly and confidently achieve the optimal dose for the patient. In this regard,
venlafaxine can be initiated at a clinically effective dose from the beginning. If the patient fails to respond to this dose, there is evidence that increased
antidepressant efficacy can be achieved by increasing the dose rather than having to resort to an augmentation strategy or switch to another class of
antidepressants. In the immediate release form,
venlafaxine has proven
antidepressant efficacy when using a twice-or three-times-a-day schedule. A
sustained release formulation is expected to be marketed soon and will permit once-a-day-dosing.