NARIs are normally activating. Depressive insomniacs, on the other hand, may benefit more from dual-action mirtazapine (Remeron) or nefazodone (Serzone). Mirtazapine, a relative of mianserin, is a relatively new drug. It stimulates noradrenaline and serotonin release while also blocking two specific (5-HT2 and 5-HT3) serotonin receptors. Unfortunately, it tends to have a somewhat sedative effect. This effect is good for agitated depressives and insomniacs but scarcely a recipe for life-affirmation. Nefazodone is another (mainly) "serotonergic" agent. It strongly inhibits the reuptake of serotonin while showing 5-HT2-receptor antagonism. This may be useful for anxious depressives; but again it may cause feelings of weakness, drowsiness and lack of energy. It is less likely to cause priapism than its older cousin trazadone (Desyrel).
Dopaminergically-augmented venlafaxine (Effexor), which blocks in order of potency the reuptake of serotonin, noradrenaline and dopamine respectively, offers another opening for creative psychopharmacology. Venlafaxine is a phenethylamine; thus it's a benign chemical cousin of MDMA. Such a combination-therapy remains clinically unexplored. Taken on its own, venlafaxine acts primarily as a serotonin re-uptake inhibitor. At the high-level doses most suitable for melancholic and hypersomnic temperaments, its noradrenergic (and weakly dopaminergic) action becomes more pronounced.
Phosphodiesterase-inhibitors, both selective (e.g. rolipram) and unselective, are another under-used option. Next century will take us much closer to the real intra-cellular action; for it is here that our minds will ultimately be healed, genetically or otherwise.
