Reboxetine; Adrafinil; Modafinil

Reboxetine (Edronax) is a well-tolerated , highly selective "noradrenergic" agent. Crudely, whereas serotonin plays a vital role in mood, noradrenaline is essential to maintaining drive and the capacity for reward. There's a fair bit of evidence that chronically depressive people have dysfunctional and atypical noradrenergic systems - particularly their alpha 2 and beta-adrenoceptors. Reboxetine itself doesn't have the disruptive effects on cognitive function or psychomotor performance so annoyingly typical of older clinical mood-brighteners. Indeed the new NorAdrenaline Reuptake Inhibitors (NARIs) are probably under-used and under-hyped. NARIs - and dopaminergics like amineptine (Survector) - may be especially good for drive-deficient "anergic" states where the capacity for sustained motivation is lacking; and for melancholic depressives with a poor ability to cope with stress. Perhaps surprisingly, preliminary studies suggest reboxetine can actually reverse tranylcypromine-induced hypertensive crises. The "cheese effect" is usually triggered by ingesting tyramine-rich foods. Thus NARIs plus MAOIs may prove a potent form of combination-therapy.

Depressive hypersomniacs who fare poorly on SSRIs, or can't get hold of amineptine or EC-licensed reboxetine, might consider trying a so-called eugeroic ("good arousal") agent instead; more adventurous souls may wish to combine the two. Alpha-1 adrenergic agonists like adrafinil and modafinil are centrally-acting stimulants which can brighten mood and sharpen mental focus. They stimulate the noradrenergic post-synaptic receptors and thereby boost alertness, activity and energy. At sensible dosages, they are remarkably free of side-effects. However, the approval process in the USA is so slow, costly and bureaucratic, and the marketing hurdles typically so formidable, that foreign companies are often deterred from seeking FDA acceptance. [modafinil was licensed by the FDA as Provigil for the treatment of narcolepsy in Dec 1998 ] So elderly people continue to suffer the prescription of mildly dementing anticholinergics like the dumb-drug tricylcic imipramine. Adrafinil, by contrast, is at least as successful as hepatotoxic Anglo-Saxon products at treating the cognitive and memory impairments of incipient senility.

Fortunately, a "French" drug like adrafinil can now be ordered over the Net; but it ought to be available at the local corner store. It has the commercial disadvantage of being very cheap.