Dual serotonin and noradrenaline reuptake inhibitors: Focus on their differences

There are three non-tricyclic dual serotonin (5-HT) and noradrenaline (NA) reuptake inhibitors (SNRIs) currently used in human therapeutics for psychiatric disorders. These medications differ in their in vitro potency to inhibit 5-HT and NA reuptake with differential ratios of activity. Using in vivo studies carried out in laboratory animals, which better reflect human physiology than experiments using lysed tissue in a test tube, venlafaxine is about three times more potent on 5-HT than NA reuptake, duloxetine five times, and milnacipran is about twice more potent on NA than 5-HT reuptake. Sustained administration of SNRIs induces different adaptive effects on presynaptic 5-HT and NA receptors controlling the function of 5-HT and NA neurons, suggesting that they may differentially affect transmission of these two neuronal systems. In the treatment of depression, SNRIs appear to have similar effectiveness and when compared to selective 5-HT reuptake inhibitors, they generally exert a superior antidepressant effect. Taken together, these observations suggest that individual patients not responding to a SNRI may present a favourable response to another agent within that family. SNRIs have different pharmacokinetic properties and exert distinct effects on the activity of liver metabolic enzymes. These features of SNRIs can help clinicians tailor treatment to individual patients.