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.

Bupropion; Amineptine

Bupropion (Wellbutrin) is possibly less effective than nomifensine. Yet it's useful because it lacks the adverse effects on sexual function characteristic of the SSRIs. In some subjects, in fact, libido, arousal, and the intensity and duration of orgasm may actually increase. Bupropion mildly blocks the reuptake, but diminishes the release, of dopamine. This may account for reports of its diminished propensity to induce mania in the genetically susceptible. Its active metabolites block the reuptake of noradrenaline. Chewed as a gum, bupropion is good for giving up smoking. Scandalously, it isn't licensed and marketed in Europe.
Amineptine (Survector) is a clean-ish, (relatively) selective dopamine reuptake blocker. Higher doses promote dopamine release too. Amineptine is liable occasionally to cause spontaneous orgasms. It is a mild but pleasant psychostimulant and a fast-acting mood-brightener. Unlike other tricyclics, it doesn't impair libido or cognitive function. Unlike typical stimulants and other activating agents, it may actually improve sleep architecture.
Scandalously, amineptine isn't licensed and marketed in Britain and America. For it is feared it might have "abuse-potential".