Atherosclerosis of the vasculature feeding the brain can lead to a condition known as cerebrovascular insufficiency. This chronic low-grade ischemia can impair memory or otherwise mimic dementia. It can also produce a syndrome resembling depression. This syndrome is surprisingly little discussed in the United States but is much more widely recognized in Europe. The treatment is obviously the same as for atherosclerosis anywhere in the body — elimination of the underlying dietary and lifestyle causes (especially sedentariness) and addition of supportive nutrients and practices (like meditation).
Ginkgo biloba (ginkgo) leaf extracts have been very rigorously shown to help alleviate cerebrovascular insufficiency symptoms. This is almost certainly due to ginkgo’s ability to reduce the underlying atherosclerosis and improve neuron function despite ischemia. It also seems to stimulate blood flow to the brain, perhaps by acting on blood vessels. The usual dose of ginkgo standardized extract is 80-160 mg two or three times per day. It should be used attentively in patients taking anticoagulants as the combination occasionally but rarely may have a synergistic effect and cause bleeding.
Gingko has also been shown to improve mood and depression in the elderly. Gingko’s effect in depression is “semi-hidden” in studies that on the surface deal more with cognitive function but mental depression and mood are shown to improve. One study of 60 hospitalized patients with cerebral insufficiency and the leading symptom of depressive mood showed significant improvements in a double-blind study of ginkgo extract lasting six weeks. Limited data suggest that depression in dementia responds to antidepressant medication, perhaps including ginkgo. At least one trial has shown that ginkgo can directly relieve depression not necessarily related to cerebrovascular insufficiency in the elderly. There is no evidence that ginkgo is useful for idiopathic major depression in younger persons. Indeed, one study of ginkgo in younger adults with seasonal affective disorder found it useless. However, it might be useful as an adjunct therapy to prevent sexual side effects of allopathic antidepressant drugs. Other botanicals that help in atherosclerosis and may relieve cerebrovascular insufficiency with concomitant depression in the elderly include Allium sativum (garlic) bulb, Rosmarinus officinalis (rosemary) leaf, and Zingiber officinale (ginger) rhizome. None of these have been specifically studied for this particular syndrome.
St. John’s Wort
German and now U.S. research has established beyond a doubt that extracts of Hypericum perforatum (St. John’s wort) flowering tops are effective antidepressants. A meta-analysis of clinical trials confirmed that St. John’s wort extracts are as effective as several synthetic antidepressant drugs and superior to placebo for people with mild to moderate depression. There is also at least one study showing that relatively high doses of St. John’s wort extract is helpful for people with severe depression. St. John’s wort was also found effective in people with seasonal affective disorder in an open clinical trial, and combining it with phototherapy was not dangerous (though it did not enhance the benefits of that therapy). It has shown promise for relieving depression in alcoholics with gastritis in a preliminary Russian clinical trial.
A large share of the highly limited resources for research on botanical medicines is being focused on St. John’s wort, including a large double-blind study funded by the National Center for Complementary and Alternative Medicine (NCCAM). Many studies firmly establish St. John’s wort efficacy, and only the most conservative would claim it is ineffective. It is unfortunate that research resources were not instead invested in studies on other interesting botanical remedies for depression. We believe the only areas of research that are truly needed for St. John’s wort at this point are more definitive studies on its mechanism of action, the efficacy of other similar species (e.g., Hypericum calycinum or rose of Sharon), and the best way to administer it.
The optimal dose form of St. John’s wort is unknown. Prior research focused on extracts standardized to 0.3% hypericin, pseudohypericin, and related dianthrones. However, it has recently become clear that hyperforin and possibly flavonoids in St. John’s wort are just as important as hypericin in the antidepressant activity of the herb, if not more important. In addition, red food color can be added to the extract to fool the usual standardization assay for hypericin that assays the red color of this compound. Unscrupulous manufacturers thus were selling far inferior encapsulated extracts almost devoid of hypericin. Extracts standardized to 5% hyperforin are starting to become popular and common. The dose of standardized extracts is 300 mg three times per day (up to double this dose in severe cases). The usual dose of tincture is 3-5 ml three times per day. There are almost no studies on the efficacy of crude extracts like tinctures of infusions of St. John’s wort. Although claims are often made that standardized extracts are superior to crude extracts, no direct comparative data currently exist to support those claims. Given the multifactorial nature of St. John’s wort’s active constituents and mechanisms of action, it is entirely possible that a crude extract would be comparable to or better than a standardized extract in efficacy.
St. John’s wort is generally very safe. In a systematic review of its adverse effects in a pool of 35,562 patients it ranged from 0 to 5.75, which was comparable to placebo. In a review of 16 postmarketing studies, it was deemed to be significantly safer than synthetic antidepressants. The risk of phototoxicity at antidepressant doses is minimal to nil, as was shown in a study in people using phototherapy combined with St. John’s wort, discussed above. Hypericum’s constituents do induce cytochrome P450 enzymes, possibly CYP 3A4 or 2D6, though study results have not been consistent on this point. Nevertheless, there are case studies suggesting St. John’s wort may interfere with cyclosporine (Sandimmune), digoxin (Lanoxin), indinavir (Crixivan), warfarin (Coumadin), and theophylline. There is some weak evidence for the danger of combining St. John’s wort with pharmaceutical antidepressants, and it may be wiser to have the patient choose one or the other rather than combining the two. Based on the fact that SSRIs can affect thyroid levels, a study attempted to look at St. John’s wort’s effect on thyroid function. In 74 patients (half with elevated thyroid-stimulating hormone [TSH] levels, half with normal levels), six had taken St. John’s wort regularly before a thyroid-stimulating hormone test. Four had elevated thyroid-stimulating hormone levels and two had normal levels. The researchers acknowledged that no link between St. John’s wort and thyroid dysfunction had been shown but considered the data to suggest that it, like SSRs, might cause a thyroid-related adverse effect when used long term. Thyroid-stimulating hormone levels rose in these individuals; two were diagnosed as hypothyroid and two already taking levothyroxine required a dose increase.
Crocus sativus (saffron), aside from being a popular spice, has a long history of use as an excellent digestive aid that reduces stomach aches, increases appetite, and has antispasmodic effects on both the intestines and the kidneys. In Persian folk medicine, it is also used as an antidepressant.
In one study of 40 people with mild to moderate depression, 30 mg of extracted saffron was compared with 20 mg/day of fluoxetine for six weeks. The drug and the herb had similar effects and showed no differences in terms of side effects. Another randomized, double-blind study compared 30mg/day saffron with 100mg/day of imipramine, again for six weeks. Both groups showed significant improvement with symptoms of dry mouth and sedation being greater in the imipramine group. Since these, three other double-blind trials used the same dose of saffron compared to placebo or various antidepressants, again showing good efficacy and a lack of adverse effects.
Saffron has also shown an antidepressant effect in animal studies. Saffron capsules do not appear to be readily available commercially in the United States at this time. In the clinical studies, a tincture of saffron was prepared (120g saffron percolated in 80% ethanol and dried by evaporation to a powder). The Eclectics also prepared a tincture of saffron. They macerated 100 g saffron in 100 ml diluted alcohol and then percolated it until they obtained 1 L of tincture. The tincture was used as an emmenagogue, as a diaphoretic, and for hysteria at a dose of 1-3 drams. It may not have been widely used as a medicine in the United States because much of the saffron on the market was reportedly adulterated.