In the companion article in this issue of TCPR, we reviewed some recent high-profile disappointments in the world of natural medications.

Nonetheless, there are several natural treatments out there that may be helpful in psychiatry. Recently, the British Journal of Psychiatry published a review of “complementary medicines in psychiatry,” (Br J Psychiatry 2006;188:109-121). Based on this paper and our own review of recent better quality studies, TCPR offers the following list of potentially useful natural treatments.

Omega-3 Fatty Acids. The American Heart Association believes strongly in omega-3 fatty acids, and recommends that just about everybody take them in one form or another in order to protect against cardiovascular disease (http://www.americanheart.org/presenter.jhtml?identifier=4632). Their value in psychiatry is gradually becoming clearer. Several recent placebo controlled trials have endorsed omega-3, especially the variety known as EPA (eicosapentaenoic acid), as an effective treatment for unipolar depression (Am J Psychiatry 2002;159:477-479, Arch Gen Psychiatry 2002;59:913-919) and bipolar depression (Br J Psychiatry 2006;188:46-50).
Dose: Variable, but recent studies have reported efficacy at relatively low doses of 1-2 g of EPA QD.
Safety issues: There have been cases of mania and hypomania in bipolar patients who took certain omega-3 preparations without a concomitant mood stabilizer.

SAM-e. A favorite of Italian psychiatrists, SAM-e has generally performed as well as the tricyclics to which it is usually compared in double-blind studies (see review of older studies by Alpert and Mischoulon in Natural Medications for Psychiatric Disorders, Lippincott Williams & Wilkins, 2002, and more recently Am J Clin Nutr 2002;76:1172-1176). Efficacy seems more reliable when given as an IM injection, but high oral doses have good evidence as well.
Dose: 1600 mg QD.
Safety issues: Potential for mania, hypomania, and anxiety in bipolar patients.

St. John’s Wort. St. John’s Wort (SJW) has been through the wringer in the U.S. Quite effective on the pages of European journals, it has over 30 positive randomized controlled trials under its belt (see reviews in BMJ 1996;313:253-258 and ClinTherapeutics 2000;22:411-419), but it faltered in two high-profile studies in the U.S. (JAMA 2001;285:1978-1986; JAMA 2002;287:1807-1814). However, a couple of recent studies may be leading to SJW’s rehabilitation. One was a randomized controlled trial of SJW vs. placebo in depressed outpatients, in which SJW outperformed placebo in response rates (53% vs. 42%, p<0.05) (Am J Psychiatry 2002;159:1361-1366). The second study was conducted by the Depression Research Program at Massachusetts General Hospital, and found that SJW (900 mg QD) was more effective for depression than fluoxetine (20 mg QD) after 12 weeks of double-blind treatment (J Clin Psychopharmacol 2005;25:441-447). While neither SJW nor fluoxetine significantly beat placebo in this study, SJW came the closest, producing a lower Hamilton depression score, but at the p=0.09 level, rather than the 0.05 level used as the benchmark for statistical significance.
Dose: 300 mg TID.
Safety issues: Induces P450 3A4, which may decrease levels of cyclosporin (an immunosuppressive), indinavir (a protease inhibitor), warfarin, theophylline, digoxin, and oral contraceptives.

Folate. Low serum folate levels appear to be associated with both treatment resistance and a greater rate of relapse in depression (J Clin Psychiatry 2004;65:1090-1098). One study tested the clinical implications of this finding by randomizing 127 patients on Prozac 20 mg QD to receive augmentation with either folate 500 mcg QD or placebo. After 10 weeks, folate augmentation outperformed placebo, but only for the women in the study, possibly related to the fact that their blood folate levels rose more than the men’s levels (J Affect Disord 2000;60:121-130).
Dose: 300-500 mcg QD.
Safety issues: None.

Chromium. One psychiatrist has made championing chromium his life work (see Lifting Depression: The Chromium Connection, M. N. Mcleod, M.D., 2005, Basic Health Publications). And, in fact, there is some evidence that elemental chromium works, at least for atypical depressive symptoms such as increased appetite, carbohydrate cravings, and diurnal mood variation (Biol Psychiatry 2003;53:261-4, J Psychiatr Pract 2005;11:302-314).
Dose: 600 mcg QD.
Safety issues: None.

Kava. Most placebo-controlled trials of kava for anxiety have been positive, with significant improvement on the Hamilton Anxiety Rating Scale (see Ann Int Med 2002; 136:42-53 for a review of the earlier studies). It has also been shown to help insomnia in patients with anxiety disorders (J Affect Disord 2004;78:101-110).
Dose: 150 mg – 300 mg QD.
Safety issues: Main issue is rare liver toxicity leading in some cases to the need for liver transplantation. Because of this, kava has been withdrawn from some European markets, including the United Kingdom. The FDA hasn’t banned it here yet, but did issue a strongly-worded consumer advisory in 2002 (www.cfsan.fda.gov/~dms/addskava.html).

Maca Root. The root of a Peruvian plant that grows at an elevation of 12,000 feet in the Peruvian Andes, maca root has been reported to increase spermatogenesis and to increase libido in healthy men (see J of Endocrinol 2003;176:163-168 for a review of some of this research, most of which has been conducted in Lima, Peru). Christina Dording and David Mischoulon and their colleagues at Massachusetts General Hospital are conducting a trial of maca root for the treatment of antidepressant-induced sexual dysfunction, and Dr. Mischoulon tells TCPR that preliminary results are encouraging.
Dose: The MGH study is dosing maca at 1-3 grams QD. It is available at pharmacies and via online sources.
Safety issues: None

Ginkgo Biloba. According to the best-designed trial discussed elsewhere in this issue, ginkgo is not effective for boosting your memory if you’re healthy. The evidence for ginkgo in Alzheimer’s dementia is a little more impressive. Two good studies showed a small benefit of about 1.5 ADAS-Cog points (Pharmacopsych 2003;36:297-303, JAMA 1997;278:1327–1332), which is about half the benefit typically produced by cholinesterase inhibitors (see TCPR Aug 2005 for a review). However, two other more recent studies showed no benefit at all (Curr Alzheimer Res 2005;2:541-551, J Clin Epidemiol 2003;56:367-376).
Dose: 120 mg – 240 mg QD.
Safety issues: Small risks of bleeding and of interactions with anticoagulants.

Valerian.TCPR gave valerian the “thumbs up” when we last did an issue on natural meds in May of 2004, largely based on a European trial that found that valerian worked as well as Serax (oxazepam) 10 mg QHS in a double-blind comparative trial (Eur J Med Res 2002;25:480-486). Since then, however, it has not fared so well. A recent study found valerian as sedating as benadryl, but neither of them separated from placebo (Sleep 2005;28:1465-1471). Two other studies found valerian ineffective when compared to placebo (Phytother Res 2004;18:831-836, J Clin Psychopharmacol 2003;23:260-268).
Dose: 300 mg - 600 mg.
Safety issues: Some Valerian preparations from India and Mexico contain potent carcinogens, and are therefore relatively contraindicated.

Potentially Useful Natural Treatments
Omega-3 Fatty Acids	Antidepressant	1 – 2 g QD (EPA)
SAM-e	Antidepressant	1600 mg QD
St. John’s Wort	Antidepressant	300 mg TID
Folate	Antidepressant augmentation	300 – 500 mcg QD
Chromium	Atypical depression	600 mcg QD
Kava	Anxiolytic (note liver risk)	150 – 300 mg QD
Maca root	AD-induced sexual dysfunction	1 – 3 g QD
Promising, but recent data more mixed
Ginkgo Biloba	Alzheimer’s Dementia	120 – 240 mg QD
Valerian	Hypnotic	300 – 600 mg QHS

TCPR Verdict:
Little to lose, worth a try.