Neuropharmacology of antidepressants that modify central noradrenergic andserotonergic function: A short review

The first generation of antidepressants largely act as 'dual' action drugs in that they facilitate both noradrenergic and serotonergic activity either by blocking the reuptake of noradrenaline and serotonin (tricyclic antidep ressants) or by inhibiting the catabolism of these amines (monoamine oxidas e inhibitors). Largely as a consequence of their unacceptable side effects, these drugs have been partly replaced by the second generation drugs that showed selectivity of either the noradrenaline (viloxazine, maprotiline, re boxetine) or serotonin (fluoxetine, sertraline, etc.) transporter. While th ese second generation drugs have undoubted advantages in terms of their saf ety and tolerability, there is growing evidence that the efficacy of some o f these selective uptake inhibitors (e.g. SSRIs) in the treatment of the mo re severe forms of depression is less than that of the TCAs. This has led t o the view that 'dual action' antidepressants may offer superiority in the treatment of severe depression. Two groups of novel antidepressants have be en developed to meet the need of combining increased efficacy with safety. These include the mixed amine reuptake inhibitors such as lofepramine, venl afaxine and milnacipran and the novel tetracyclic antidepressant mirtazepin e that facilitates the functional activity of both noradrenaline and seroto nin without affecting the reuptake sites. Copyright (C) 1999 John Wiley & S ons, Ltd.