Ginkgo biloba for Depression
Ginkgo biloba for Depression
By Dónal P. O'Mathúna, PhD Dr. O'Mathúna is Lecturer in Health Care Ethics, School of Nursing, Dublin City University, Ireland. Dr. O'Mathúna reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study.
For years, ginkgo has been one of the top three best-selling herbal remedies in the United States. Ginkgo shot into public awareness after a 1997 article was published in the Journal of the American Medical Association.1 This study demonstrated that mild-to-moderate symptoms of dementia remained stable or slightly improved while patients were taking a ginkgo extract compared to patients taking placebo. Soon ginkgo was being recommended to promote many different mental capacities. In particular, its ability to enhance memory was explored. As a result, in 2002, ginkgo was the third most commonly used herbal remedy in the United States. Almost one-fourth of those who use herbal remedies stated that they used ginkgo.2 Ginkgo is the leading herbal remedy in Europe.3 Among the claims made for ginkgo is that is can relieve depression, which will be the focus of this article.
Ginkgo biloba is a tree native to southeast Asia. Believed to be the oldest living tree species, the species has been described as a "living fossil."4 Individual trees can be more than 1,000 years old. The herbal remedy is made from the leaves, which have a distinct fan shape. The leaves are soaked in alcohol and the resulting extract is dried, powdered, and made into capsules. Although references to medicinal uses of ginkgo exist in medieval Chinese texts, it was introduced into modern practice by a German physician in 1965. This physician's preparation, now called EGb 761, remains the focus of much ginkgo research. The extract is approved in Germany for the treatment of dementia.
Mechanism of Action
Like most herbal remedies, ginkgo extracts contain a large number of active ingredients. Standardized preparations have been developed in Europe based on two groups of active compounds. The extracts most commonly tested contain ginkgoflavone glycosides (16-25%), terpene trilactones (around 6%), and no more than 5 ppm ginkgolic acids (which cause allergic reactions).3
Ginkgo is believed to increase the flow of blood through arteries and veins in various tissues. A number of small clinical trials have shown that ginkgo extracts improve overall functioning in patients with peripheral arterial disease and claudication (pain in calf muscles that people with narrowed or blocked arteries get when walking). Other studies have shown that ginkgo has antioxidant properties that may minimize damage from free radicals. How it might work to relieve depression remains unclear.
The earliest trial of ginkgo for depression examined its potential to prevent the onset of seasonal affective disorder (SAD).5 A total of 27 patients were randomly assigned to received either ginkgo extract tablets or placebo. The study began about one month before seasonal depression usually started in the participants and before they had any SAD symptoms. After 10 weeks of treatment, there were no significant differences between the two groups on a depression scale or in the number who required treatment for depression.
Some studies with a primary focus on memory also have examined the impact of ginkgo on mood. One such trial randomly assigned 31 postmenopausal women to seven days of either 120 mg/d ginkgo extract or placebo.6 Some significant differences were found in tests of memory and attention. However, tests of mood and premenstrual symptoms showed no significant differences between the two groups.
Another study examined the effects of ginkgo on healthy older adults who had just completed a four-month study of ginkgo extract, 120 mg/d.7 Participants either had taken ginkgo or placebo for the previous four months and could chose whether to take placebo or ginkgo for the next six months. At the end of the study, researchers found significant improvements for mood and alertness between the ginkgo and placebo groups. The magnitudes of the improvements were greater for those who had taken ginkgo for 10 months compared to those who took it for six months or four months. However, the trial design was an open study, making its findings tentative since participants could chose the treatment they wanted.
One particular commercial product (Gincosan) contains both ginkgo (60 mg of extract) and ginseng (100 mg of extract) and its effect on mood has been studied as part of larger studies of its impact on memory. Gincosan did not produce any benefit compared to placebo in a 90-day trial where participants were given either 80 mg/d, 160 mg/d, or 320 mg/d of mixed extract.8 In another trial with 256 participants, those receiving 360 mg/d mixed extract for 12 weeks showed no mood improvements compared to those receiving placebo.9 A study of the acute effects of Gincosan gave 20 participants 320 mg/d, 640 mg/d, or 960 mg/d Gincosan or placebo. No mood improvements were reported over the course of the day.10 Most recently, a double-blind study randomized 57 postmenopausal women to either 320 mg/d Gincosan or placebo.11 After 12 weeks, no significant differences were found for depression as measured by the Hospital Anxiety and Depression scale nor for any other menopausal symptoms.
One additional trial randomly assigned 20 healthy, young volunteers to either 360 mg/d ginkgo, 400 mg/d ginseng, 960 mg/d Gincosan, or placebo. The participants were monitored over one day and given various tests for memory and mood. The ginkgo and Gincosan recipients had significant improvements in mood during the day the dose was taken.12 The two other groups reported no significant improvements in mood.
In clinical trials, few adverse effects have been observed with ginkgo extract. However, in one study, twice as many patients taking ginkgo reported intestinal problems compared to those taking the placebo.1 Postmarket surveillance in Germany found that fewer than 2% of users experienced adverse effects, with the most common ones being mild gastrointestinal disturbances and headaches.13
Ginkgo has been shown to interfere with blood clotting factors, and bleeding problems have occurred in patients also taking blood-thinning drugs, such as aspirin or warfarin. However, a controlled study of the impact of ginkgo on blood clotting in people taking warfarin showed no change in blood clotting times.14 Some evidence has suggested that ginkgo may inhibit an enzyme called monoamine oxidase (MAO). This could cause problems by exacerbating a number of other antidepressant drugs that act the same way. Since people taking both these medications also may be concerned about memory loss, they should consult their physician before taking ginkgo (or any other herbal remedy).
Many of the ginkgo studies have used the standardized preparation called EGb 761. The most usual dose is 120-240 mg/d of the standardized extract, divided into two or three doses.
Extracts of ginkgo have been shown to have a number of uses in treating memory and attention deficits associated with various cognitive diseases. However, its use to treat depression is not supported by evidence from studies published to date. Few studies are available, and most of those have found little or no benefit from ginkgo for depression. Some of these studies have involved menopausal women who did not experience any relief from ginkgo beyond that of the placebo group. Fortunately, ginkgo appears to be relatively safe to use.
Women suffering from depression should be encouraged to pursue conventional and complementary treatments that have been demonstrated to be effective and safe, but not ginkgo. Rather than searching for something to take for depression, women should be encouraged to investigate why they may be feeling depressed. Various strategies involving counseling, talking, or medical evaluations can be suggested. Depending on the degree of depression, relational or lifestyle changes may be beneficial. However, if a chemical treatment is needed, the evidence does not support the use of ginkgo.
1. Le Bars PL, et al. A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. JAMA 1997;278:1327-1332.
2. Barnes PM, et al. Complementary and alternative medicine use among adults: United States, 2002. Advance Data from Vital and Health Statistics. May 27, 2004. Available at: www.cdc.gov/nchs/data/ad/ad343.pdf. Accessed Sept. 13, 2005.
3. Sierpina VS, et al. Ginkgo biloba. Am Fam Physician 2003;68:923-926.
4. Gertz HJ, Kiefer M. Review about Ginkgo biloba special extract EGb 761 (Ginkgo). Curr Pharm Des 2004;10:261-264.
5. Lingaerde O, et al. Can winter depression be prevented by Ginkgo biloba extract? A placebo-controlled trial. Acta Psychiatr Scand 1999;100:62-66.
6. Hartley DE, et al. Effects on cognition and mood in postmenopausal women of 1-week treatment with Ginkgo biloba. Pharmacol Biochem Behav 2003;75:711-720.
7. Trick L, et al. The effects of Ginkgo biloba extract (LI 1370) supplementation and discontinuation on activities of daily living and mood in free living older volunteers. Phytother Res 2004;18:531-537.
8. Wesnes KA, et al. The cognitive, subjective, and physical effects of a Ginkgo biloba/Panax ginseng combination in healthy volunteers with neurasthenic complaints. Psychopharmacol Bull 1997;33:677-683.
9. Wesnes KA, et al. The memory enhancing effects of a Ginkgo biloba/Panax ginseng combination in healthy middle-aged volunteers. Psychopharmacology (Berl) 2000;152:353-361.
10. Kennedy DO, et al. The dose-dependent cognitive effects of acute administration of Ginkgo biloba to healthy young volunteers. Psychopharmacology (Berl) 2000;151:416-423.
11. Hartley DE, et al. Gincosan (a combination of Ginkgo biloba and Panax ginseng): The effects on mood and cognition of 6 and 12 weeks' treatment in post-menopausal women. Nutr Neurosci 2004;7:325-333.
12. Kennedy DO, et al. Modulation of cognition and mood following administration of single doses of Ginkgo biloba, ginseng, and a ginkgo/ginseng combination to healthy young adults. Physiol Behav 2002;75:739-751.
13. Tesch BJ. Herbs commonly used by women: An evidence-based review. Am J Obstet Gynecol 2003;188:S44-S55.
14. Engelsen J, et al. Effect of coenzyme Q10 and Ginkgo biloba on warfarin dosage in stable, long-term warfarin treated outpatients. A randomised, double blind, placebo-crossover trial. Thromb Haemost 2002;87:1075-1076.O'Mathuna DP. Ginkgo biloba for depression. Altern Ther Women's Health 2006;8(1):1-3.
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