The Good Drug Guide : new mood-brighteners and antidepressants
HYPERICUM
Hypericum is important for a different reason altogether. Many constitutionally unhappy people refuse to have anything to do with orthodox Western medicine. They won't take "unnatural" pharmaceutical products at all. In consequence, they spend much of their lives trapped in a squalid psychochemical ghetto of low spirits. The only sort of remedy that they'll conceivably contemplate taking must carry a "natural" label and soothingly "herbal" description.
Unfortunately, most folk remedies are only marginally effective. Our drug-metabolising enzymes are the product of an evolutionary arms race to counteract plant toxins. For plants tend to manufacture psychotropics because they poison or debilitate creatures tempted to eat them - not to heal our psychic woes. The Wisdom Of Nature is a quaint piece of make-believe. Perversely, several of the natural remedies that sometimes actually work - notably Cannabis sativa, Erythroxylon coca and Papaver somniferum - are now illegal to consume. Other "natural" interventions such as bright light therapy combined with good sleep discipline may be of limited use. But two options worth exploring are SAMe and St John's wort.
Hypericum, the active ingredient in St John's wort, appears to be an effective mood-brightener and anxiolytic - by today's standards at least. Its side-effect profile and efficacy in mild-to-moderate depression compares favourably with its synthetic counterparts. Hypericum's blend of serotonin-reuptake inhibiting and (mild) MAO-inhibiting properties (not a combination otherwise to be explored with potent synthetics: the risk of the potentially fatal serotonin syndrome is too great) contributes to - without wholly explaining - its generally benign effects. Once again, much more research is needed, preferably not bankrolled by the makers of lucrative competing products. Thus a German trial published in the British Medical Journal in February 2005 reported that a proprietary standardised extract of hypericum/St John's wort was more effective and a better tolerated treatment of moderate to severe depression than the SSRI paroxetine (Paxil). This runs counter to the negative findings of the 2001 U.S. trial sponsored by the makers of the SSRI sertraline (Zoloft) - which concluded that for moderate to severe depression, St John's wort was no better than a placebo. Faith in the integrity of biological psychiatry would be greater if the single strongest predictive factor in the outcome of any published clinical trial wasn't the identity of the funding body. A Cochrane Review published in October 2008 found that hypericum extracts used to treat major depression had similar efficacy to standard antidepressants but fewer side-effects.
INOSITOL
One further remedy, albeit at "unnatural" doses, is worth noting. Inositol levels tend to be low in depressives and high in euphoric people. Taking myo-inositol as a food supplement in doses of 12g and more per day represents perhaps the first successful use of the precursor strategy for a second messenger rather than a neurotransmitter in the search for long-term mood-brightening agents. Inositol and its derivatives serve as messenger molecules within the nervous system. The molecule itself is a naturally occurring isomer of glucose. It is a key intermediate of the phosphatidyl-inositol cycle. This is a second-messenger system used by several noradrenergic, serotonergic and cholinergic receptors. Adult westerners typically consume about one gram of inositol per day in their food. The richest dietary sources are fruits, nuts, beans and grains. The mood-darkening ("stabilising") effect of lithium in manically euphoric people may be explicable in terms of its inositol-depleting effect. Potentially, if taken in high doses, inositol seems to be a good way of lightening the spirits and diminishing anxiety in "euthymic" and depressed people alike. Dosages of even 50g and more reportedly produce no toxic side-effects. This regimen shouldn't be attempted unsupervised by people with a history of bipolar disorder. As usual, much more research is in order. One "problem" is that naturally-occurring compounds - such as inositol and SAMe - can't be patented. So the scope for high profit-margins is diminished. Progress is unlikely to be brisk.