The commonly recognised legal and illegal recreational drugs offer poor prospects for sustained biological mood-enhancement. So what about the heterogeneous group of compounds uninvitingly labelled as anxiolytics and antidepressants? Have they potentially anything significant to add to most people's quality of life? Official medical doctrine says no. Allegedly, only sufferers from clinically-sanctioned psychiatric disorders will benefit from such agents; though in recent years it has at last been formally recognised that depressive disorders are under-diagnosed and under-treated even by the twentieth century's abjectly poor standards of acceptable ill-being. Most of humanity, however, still doesn't fit any of the official diagnostic boxes. Can "diagnostic creep" triumph over therapeutic minimalism and enhance their quality of life? Yes. Must the goal of pharmacotherapy be as limited as Freud's aspiration for psychotherapy: "to transform hysterical misery into common unhappiness"? No.
First, the boring but crucial preliminaries. Optimal nutrition and exercise will increase the efficacy of all the potential life-enhancers touted here. A rich supply of precursor chemicals (e.g. tryptophan, the rate-limiting step in the production of serotonin) can also reduce their effective dosages. By choosing to eat an ideal "stone-age" diet rich in organic nuts, seeds, fruit and vegetables, and drastically reducing one's consumption of saturated fat (red meat, fried foods), sugar (sweets etc) and hydrogenated oils (found in margarine and refined vegetable oils), then one's baseline of well-being - or at least relative ill-being - can be sustainably lifted. Visitors to HedWeb probably don't expect to be assailed by sermons on the benefits of exercise any more than food-faddism. Yet regular and moderately vigorous physical exertion releases endogenous opiates, enhances serotonin function, stimulates nerve growth factors, and leads to a livelier, better-oxygenated brain.
Alas, clean living and wholesome thoughts typically aren't enough. We need stronger medicine to flourish. At first glance, however, the standard, State-rationed chemicals aren't a brilliant bunch.
The so-called minor tranquillisers, the benzodiazepines such as diazepam (Valium) and the shorter-acting temazepam, are sometimes useful but still dreadfully crude anti-anxiety agents. They act primarily on the GABA (gamma aminobutyric acid) receptor complex. GABA functions as the main inhibitory neurotransmitter in the central nervous system. The progress of molecular biology and neurogenetics in unravelling the fiendish complexity of GABA's receptor sub-types should eventually allow more targeted compounds to be developed. These more selective and site-specific drugs will lack the sedative and hypnotic properties of today's marketed brands. In the meantime, benzodiazepines in current use tend to induce dependence, dull consciousness and impair the intellect. So there's not much chance of radical life-enrichment here.
Buspirone (Buspar), is somewhat more promising. It acts on an autoreceptor subtype of serotonin. This means it has mood-brightening properties too; and hence it is useful in anxious depressive states. Buspirone lacks the intellect-clouding effects of other clinical and alcoholic anti-anxiety agents. Yet its weak and equivocal effects on sub-types of dopamine function, while useful for the purposes of commercially touting its lack of "abuse potential", mean it isn't very exciting or especially effective.
The so-called anti-depressants fall into several categories. Their mood-brightening effect is correlated with alterations in the concentration of catecholamines and/or serotonin in the central nervous system and the long-term receptor re-regulation these changes provoke.
The tricyclics, prototypically imipramine (Tofranil), and their allies are relatives of the neuroleptic drug chlorpromazine. Chlorpromazine is also known as Largactil, the notorious "chemical cosh". Tricyclics block to varying degrees the reuptake of serotonin and noradrenaline into the nerve cell terminals from where they are released. Perhaps unsurprisingly given their parentage, they are all dirty drugs, though some are dirtier than others.
Their anti-cholinergic effects harm memory and intellectual performance. Their anti-histamine action induces drowsiness and sedation. Their adverse effect on cardiac function makes them dangerous in overdose. Most "euthymic" volunteers on whom they have been tested don't like their dulling effects of consciousness. Unlike chlorpromazine, the tricyclic antidepressants don't noticeably block the dopamine receptors. But with one notable exception, they do precious little to stimulate dopamine function either. Hence they're not much fun even for the severely depressed people who can benefit from taking them. For three decades they were the mainstay of the treatment of clinically-acknowledged depression. They contributed to the widely-held medical opinion that anything classed as an antidepressant won't help "normal" people; unless of course they were "really" depressed. Basically, tricyclics are cheap, nasty and best avoided.
Much better, but still in some ways deeply flawed, are the selective serotonin reuptake inhibitors.
Serotonin, "the civilising neurotransmitter", plays a vital role in mood, memory, appetite, sleep, pain perception and sexual desire.
Fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft), and citalopram (Cipramil, Celexa) are currently licensed and marketed. More of their "me-too" relatives are on the way from pharmaceutical companies eager for a lucrative piece of the action. The SSRIs all differ in their half-lives, chemical structure and precise specificities. Their functional effects are broadly similar. Their mood-brightening, resilience-enhancing and anti-anxiety properties really can make a modest percentage of the population feel "better than well". As a class, they don't have the physically unpleasant and cognitively debilitating anti-cholinergic effects of the tricyclics. A much larger section of the community - folk who daily knock back huge quantities of ethyl alcohol in the socially accepted fashion - could surely gain from the durably enhanced serotonin function SSRIs can yield. Such a switch would necessitate a big change in marketing strategy.
The beneficent properties of the SSRIs are celebrated in Peter Kramer's contemporary classic Listening to Prozac. Kramer has written a remarkably honest book. It's a discursive memoir by a therapist who is forced to admit that many of his clients seemed rapidly to fare far better on a pill than on his industrial-strength regimen of caring talk-therapy. Kramer's discussion of "cosmetic psychopharmacology" and "designer personalities", however, enraged traditionalists. For chemical Calvinist orthodoxy finds the notion that people should have a right pharmacologically to choose who and what they want to be profoundly offensive.
Two common problems limit the usefulness of SSRIs, at least when taken on their own. The problems stem from the indirect inhibitory effect of Prozac-style drugs on dopamine function, a consequence of deliberate selective targeting on the functional enhancement of subtypes of serotonin pathway.
First, SSRIs can compromise libido and sexual performance. This isn't always a disadvantage in over-excitable young males. It can still be a very distressing phenomenon for people too embarrassed to talk about it. Technical performance difficulties can sometimes be counteracted by taking (the alpha-2 adrenergic agonist) yohimbine; the phosphodiesterase inhibitor sildenafil (better known as the sexual rocket-fuel Viagra); or a dopamine agonist, licit or otherwise, before bedtime action. Yet this is scarcely an ideal solution.
Second, though some subjects may feel mildly euphoric, in other users the SSRIs serve more as mood-stabilisers and -flatteners in their lives. By increasing the user's emotional self-sufficiency, too, SSRIs may subtly change the "balance of power" in personal relationships - for good or ill. In some cases, SSRIs may even act as thymoanaesthetisers which diminish the intensity of felt emotion; by contrast, a mood-brightening serotonin reuptake-enhancer like tianeptine may intensify emotion instead. Affective flattening may be welcome to someone in the pit of unmitigated clinical depression. It is scarcely a life-enriching property for "normal" people who lack any convenient diagnostic category which acknowledges their malaise.
