Antidepressant drugs: does it matter if they inhibit the reuptake of noradrenaline or serotonin?

The current popularity of the selective serotonin reuptake inhibitors (SSRIs) for the treatment of depression should not conceal the fact that noradrenergic neurones also seem to influence depressed mood. Selective noradrenaline reuptake inhibitors (NRIs) such as reboxetine thus seem to be at least as effective as the SSRIs. It has been suggested that NRIs influence depression by indirectly facilitating serotonergic transmission, or that SSRIs act by facilitating noradrenaline; however, the marked differences between SSRIs and NRIs with respect to effects and side-effect profile do not support any of these assumptions, but rather suggest that SSRIs and NRIs influence depression by parallel, independent pathways. In this review the possibility that certain symptoms within the depressive syndrome (and certain subtypes of depression) respond better to NRIs, whereas other symptoms (and subtypes) respond better to SSRIs, will be discussed. In addition, the putative usefulness of NRIs for indications other than depression will be commented upon.