SNRIs are a class of antidepressants characterized by a mixed action on both major monoamines of depression: NE and serotonin. In essence, SNRIs are improved TCAs with less off-target activity, e.g., muscarinic, histaminic and ^-adrenergic receptors, and MAOI. The combination of inhibition of 5HT and NE uptake confers a profile of effectiveness comparable to TCAs and is reported to be higher than SSRIs, especially in severe depression. SNRIs are purported to be better tolerated than TCAs and more similar to SSRIs without the associated sexual dysfunction seen with the latter. Venlafaxine (38) and milnacipran (4) have been approved so far, and several others are in development. They are active on depressive symptoms, as well as on certain comorbid symptoms (anxiety, sleep disorders) frequently associated with depression. SNRIs appear to have an improved rate of response and a significant rate of remission, decreasing the risk of relapse and recurrence in the medium and long term and address two of the current goals of antidepressant treatment. Reboxetine (39) is another SNRI, which was approved in Europe for the treatment of major depression but is not available in the USA.
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