Natural Treatments for Depression

St. John's wort

St. John's wort is a herbal preparation from the Hypericum perforatum plant. It has long been used in folk medicine, and today it's widely prescribed in Europe to treat anxiety and depression. In the United States, it's sold in health food stores and pharmacies in the form of tablets or tea.

St. John's wort has been shown to be effective in patients with mild to moderate depression. This herb appears to act as a weak SSRI and may have an affinity for sigma receptors as well. Preliminary studies suggest that St. John's wort might work by preventing nerve cells in the brain from reabsorbing the chemical messenger serotonin, or by reducing levels of a protein involved in the body's immune system functioning.

Studies have compared TCAs imipramine (Tofranil) and amitriptyline (Elavil) with St. John's wort in cases of mild to moderate depression and found no statistical differences between groups as evaluated by the Hamilton Depression Scale. One-third fewer side effects were noted in the subjects taking St. John's wort, compared with the subjects taking amitriptyline.

St John's Wort was tested in a double-blind study of 105 patients suffering from mild-moderate depression. The patients were male and female, 20 to 64 years of age, and diagnosed with neurotic depression or temporary depressive mood. They were then divided into two groups and monitored over a period of four weeks. One group were given 300 mg of St John's Wort extract, three times daily, and the other group were given a placebo. All of the patients were given psychiatric evaluations before the start of the study, and after two and four weeks of treatment. The results revealed that, after the four weeks, 67% of the Hypericum group had responded positively to the treatment without any adverse side effects whereas only 28% of the placebo group showed any signs of improvement.

St. John's wort has not been studied for management of severe or treatment-resistant depression.

Side effects include dry mouth, dizziness, digestive problems, fatigue, headache and sexual problems. In most cases, signs and symptoms are mild. Of concern is that St. John's wort can interfere with the effectiveness of prescription medications, including antidepressants, drugs to prevent organ rejection in people who've had transplants.

Scientific evidence of St. John's wort effectiveness

• 1. Wheatley D. LI 160, an extract of St. John's wort, versus amitriptyline in mildly to moderately depressed outpatients--a controlled 6-week clinical trial. Pharmacopsychiatry 1997;30(suppl 2):77-80.
• 2. Harrer. G, and Sommer.H., Treatment of Mild/Moderate Depressions With Hypericum, Phytomedicine, Vol. 1, 1994, pp 3 - 8.
• 3. Kasper S, Anghelescu IG, Szegedi A, Dienel A, Kieser M. Superior efficacy of St John's wort extract WS 5570 compared to placebo in patients with major depression: a randomized, double-blind, placebo-controlled, multi-center trial [ISRCTN77277298]. BMC Med. 2006 Jun 23;4:14. PubMed
• 4. Randlv C, Mehlsen J, Thomsen CF, Hedman C, von Fircks H, Winther K. The efficacy of St. John's Wort in patients with minor depressive symptoms or dysthymia--a double-blind placebo-controlled study. Phytomedicine. 2006 Mar;13(4):215-21. Epub 2006 Jan 19. PubMed
• 5. Fava M, Alpert J, Nierenberg AA, Mischoulon D, Otto MW, Zajecka J, Murck H, Rosenbaum JF. A Double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder. J Clin Psychopharmacol. 2005 Oct;25(5):441-7. PubMed
• 6. Simeon J, Nixon MK, Milin R, Jovanovic R, Walker S. Open-label pilot study of St. John's wort in adolescent depression. J Child Adolesc Psychopharmacol. 2005 Apr;15(2):293-301. PubMed
• 7. Francis AJ. Antidepressant action of St. John's Wort, Hypericum perforatum: a test of the circadian hypotheses. Phytomedicine. 2005 Mar;12(3):167-72. PubMed
• 8. Szegedi A, Kohnen R, Dienel A, Kieser M. Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine. BMJ. 2005 Mar 5;330(7490):503. Epub 2005 Feb 11. PubMed
• 9. Lecrubier Y, Clerc G, Didi R, Kieser M.Efficacy of St. John's wort extract WS 5570 in major depression: a double-blind, placebo-controlled trial. Am J Psychiatry. 2002 Aug;159(8):1361-6. PubMed
• 10. Kalb R, Trautmann-Sponsel RD, Kieser M. Efficacy and tolerability of hypericum extract WS 5572 versus placebo in mildly to moderately depressed patients. A randomized double-blind multicenter clinical trial. Pharmacopsychiatry. 2001 May;34(3):96-103. PubMed

Licorice

Licorice is a very powerful antidepressant. Its role was overshadowed by the media attention to St. John's Wort. At least eight licorice compounds are monoamine oxidase (MAO) inhibitors. MAO inhibitors are compounds capable of potent antidepressant action.

Scientific evidence of Licorice effectiveness

• No clinical studies on humans have been conducted to prove or disprove Licorice effectiveness for depression

Ginkgo biloba

Ginkgo biloba, while clearly not a primary treatment of choice for most patients with major depression, may be considered an alternative for elderly patients with depression resistant to standard drug therapy. This is because depression is often an early sign of cognitive decline and cerebrovascular insufficiency in elderly patients. Frequently described as resistant depression, this form of depression is often unresponsive to standard antidepressant drugs or phytomedicines like St. John's wort. One study showed a global reduction in regional cerebral blood flow in depressed patients older than 50 when compared with age-matched, healthy controls.

In the study 40 patients, ages 51 to 78, with a diagnosis of resistant depression (insufficient response to treatment with tricyclic antidepressants for at least three months), were randomized to receive either Ginkgo biloba extract or placebo for eight weeks. Patients in the ginkgo group received 80 mg of the extract three times daily. During the study, patients remained on their antidepressant drugs. In patients treated with ginkgo, there was a decline in the median Hamilton Depression Scale scores from 14 to 7 after four weeks. This score was further reduced by 4.5 at eight weeks. There was a one-point reduction in the placebo group after eight weeks. In addition to the significant improvement in symptoms of depression for the ginkgo group, there was also a noted improvement in overall cognitive function. No side effects were reported.

Scientific evidence of Licorice effectiveness

• 1. Schubert H, Halama P. Depressive episode primarily unresponsive to therapy in elderly patients: efficacy of Ginkgo biloba extract (EGb 761) in combination with antidepressants. Geriatr Forsch 1993;3:45-53.
• 2. Kalkunte SS, Singh AP, Chaves FC, Gianfagna TJ, Pundir VS, Jaiswal AK, Vorsa N, Sharma S. Antidepressant and antistress activity of GC-MS characterized lipophilic extracts of Ginkgo biloba leaves. Phytother Res. 2007 Jul 18. PubMed

Siberian Ginseng

Siberian ginseng improves the balance of important neurotransmitters (including serotonin, dopamine, norepinephrine, and epinephrine) in the brain. In studies using laboratory animals, Siberian ginseng has been shown to act as an MAO inhibitor. In people with depression, the herb helps to improve their sense of well-being.

Scientific evidence of Licorice effectiveness

• No clinical studies on humans have been conducted to prove or disprove Licorice effectiveness for depression

SAM-e (S-Adenosylmethionine)

Another potential antidepressant is SAMe (also called SAM-e, S-Adenosylmethionine). SAMe is a chemical substance, found naturally in all human cells. It plays a role in the many methylation reactions of the body, including gene expression, cell membrane homeostasis, and hormone and neurotransmitter synthesis. It is thought to increase levels of serotonin and dopamine.

SAMe has been studied for decades internationally and is approved as a prescription drug in Spain, Italy, Russia and Germany. Europeans use it primarily for depression and arthritis. It is often touted as a depression remedy that is nontoxic, without side effects, and better and faster than traditional medications. In the United States SAMe is sold as an over-the-counter dietary supplement.

Some studies have found SAM-e to be more effective than a placebo, but no more effective than treatment with antidepressant medications.

SAM-e can cause nausea and constipation.

Scientific evidence of SAM-e effectiveness

• 1. Salmaggi P, Bressa GM, Nicchia G, Coniglio M, La Greca P, Le Grazie C. Double-blind, placebo-controlled study of S-adenosyl-L-methionine in depressed postmenopausal women. Psychother Psychosom. 1993;59(1):34-40. PubMed
• 2. Bell KM, Plon L, Bunney WE Jr, Potkin SG. S-adenosylmethionine treatment of depression: a controlled clinical trial. Am J Psychiatry. 1988 Sep;145(9):1110-4. PubMed
• 3. Lipinski JF, Cohen BM, Frankenburg F, Tohen M, Waternaux C, Altesman R, Jones B, Harris P. Open trial of S-adenosylmethionine for treatment of depression. Am J Psychiatry. 1984 Mar;141(3):448-50. PubMed
• 4. Alpert JE, Papakostas G, Mischoulon D, Worthington JJ 3rd, Petersen T, Mahal Y, Burns A, Bottiglieri T, Nierenberg AA, Fava M. S-adenosyl-L-methionine (SAMe) as an adjunct for resistant major depressive disorder: an open trial following partial or nonresponse to selective serotonin reuptake inhibitors or venlafaxine. J Clin Psychopharmacol. 2004 Dec;24(6):661-4. PubMed
• 5. Pancheri P, Scapicchio P, Chiaie RD. A double-blind, randomized parallel-group, efficacy and safety study of intramuscular S-adenosyl-L-methionine 1,4-butanedisulphonate (SAMe) versus imipramine in patients with major depressive disorder. Int J Neuropsychopharmacol. 2002 Dec;5(4):287-94. PubMed
• 6. Delle Chiaie R, Pancheri P, Scapicchio P. Efficacy and tolerability of oral and intramuscular S-adenosyl-L-methionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in 2 multicenter studies. Am J Clin Nutr. 2002 Nov;76(5):1172S-6S. PubMed
• 7. Fava M, Giannelli A, Rapisarda V, Patralia A, Guaraldi GP. Rapidity of onset of the antidepressant effect of parenteral S-adenosyl-L-methionine. Psychiatry Res. 1995 Apr 28;56(3):295-7. PubMed

5-HTP (5-Hydroxytryptophan)

One of the raw materials that your body needs to make serotonin is a chemical called 5-HTP (5-hydroxytryptophan). In theory, if you boost your body's level of 5-HTP, you should also elevate your levels of serotonin. But there is not enough evidence to determine if 5-HTP is effective and safe.

Scientific evidence of 5-HTP effectiveness

• 1. Shaw K, Turner J, Del Mar C. Tryptophan and 5-hydroxytryptophan for depression. Cochrane Database Syst Rev. 2002;(1):CD003198. PubMed
• 2. van Praag HM. In search of the mode of action of antidepressants: 5-HTP/tyrosine mixtures in depression. Adv Biochem Psychopharmacol. 1984;39:301-14. PubMed
• 3. Birdsall TC. 5-Hydroxytryptophan: a clinically-effective serotonin precursor. Altern Med Rev. 1998 Aug;3(4):271-80. PubMed

Vitamin B6 (pyridoxine)

Vitamin B6, or pyridoxine, is the cofactor for enzymes that convert L-tryptophan to serotonin and L-tyrosine to norepinephrine. Consequently, vitamin B6 deficiency might result in depression. One person volunteered to eat a pyridoxine-free diet for 55 days. The resultant depression was alleviated soon after supplementation with pyridoxine was begun.

A typical vitamin B6 dose is 50 mg/day.

In a randomized crossover trial Vitamin B6 have shown to alleviate premenstrual depression.

Scientific evidence of Vitamin B6 effectiveness

• 1. Hvas AM, Juul S, Bech P, Nexo E. Vitamin B6 level is associated with symptoms of depression. Psychother Psychosom. 2004 Nov-Dec;73(6):340-3. PubMed
• 2. Shiloh R, Weizman A, Weizer N, Dorfman-Etrog P, Munitz H. Antidepressive effect of pyridoxine (vitamin B6) in neuroleptic-treated schizophrenic patients with co-morbid minor depression--preliminary open-label trial. Harefuah. 2001 May;140(5):369-73, 456. PubMed
• 3. Doll H, Brown S, Thurston A, Vessey M. Pyridoxine (vitamin B6) and the premenstrual syndrome: a randomized crossover trial. J R Coll Gen Pract. 1989 Sep;39(326):364-8. PubMed
• 4. Bukreev VI. Effect of pyridoxine on the psychopathology and pathochemistry of involutional depressions. Zh Nevropatol Psikhiatr Im S S Korsakova. 1978;78(3):402-8. PubMed

Folic acid (Vitamin B9)

Studies suggest that Folic acid deficiency may be associated with depression more than any other nutrient. Between 15% and 38% of people with depression have low folate levels in their bodies and those with very low levels tend to be the most depressed.

Folic acid deficiency may result from dietary deficiency, physical or psychological stress, excessive alcohol consumption, malabsorption or chronic diarrhea. Deficiency may also occur during pregnancy or with the use of oral contraceptives, other estrogen preparations or anticonvulsants. Psychiatric symptoms of folate deficiency include depression, insomnia, anorexia, forgetfulness, hyperirritability, apathy, fatigue and anxiety.

Serum folate levels were measured in 48 hospitalized patients: 16 with depression, 13 psychiatric patients who were not depressed and 19 medical patients. Depressed patients had significantly lower serum folate concentrations than did patients in the other two groups. Depressed patients with low serum folate levels had higher depression ratings on the Hamilton Depression Scale than did depressed patients with normal folate levels.

Scientific evidence of Folic acid effectiveness

• 1. Ghadirian AM, Ananth J, Engelsmann F. Folic acid deficiency and depression. Psychosomatics. 1980 Nov;21(11):926-9. PubMed
• 2. Sachdev PS, Parslow RA, Lux O, Salonikas C, Wen W, Naidoo D, Christensen H, Jorm AF. Relationship of homocysteine, folic acid and vitamin B12 with depression in a middle-aged community sample. Psychol Med. 2005 Apr;35(4):529-38. PubMed
• 3. Coppen A, Bolander-Gouaille C. Treatment of depression: time to consider folic acid and vitamin B12. J Psychopharmacol. 2005 Jan;19(1):59-65. PubMed
• 4. Coppen A, Bailey J. Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial. J Affect Disord. 2000 Nov;60(2):121-30. PubMed
• 5. Taylor MJ, Carney SM, Goodwin GM, Geddes JR. Folate for depressive disorders: systematic review and meta-analysis of randomized controlled trials. J Psychopharmacol. 2004 Jun;18(2):251-6. PubMed

Magnesium

Magnesium deficiency can cause numerous psychological changes, including depression. The symptoms of magnesium deficiency are nonspecific and include poor attention, memory loss, fear, restlessness, insomnia, tics, cramps and dizziness. Plasma magnesium levels have been found to be significantly lower in depressed patients than in controls.

Magnesium has also been used to treat premenstrual mood changes. In a double-blind trial, 32 women with premenstrual syndrome were randomly assigned to receive 360 mg/day of magnesium or placebo for two months. The treatments were given daily from day 15 of the menstrual cycle until the onset of menstruation. Magnesium was significantly more effective than placebo in relieving premenstrual symptoms related to mood changes.

Scientific evidence of Magnesium effectiveness

• 1. Facchinetti F, Borella P, Sances G, Fioroni L, Nappi RE, Genazzani AR. Oral magnesium successfully relieves premenstrual mood changes. Obstet Gynecol. 1991 Aug;78(2):177-81. PubMed
• 2. Eby GA, Eby KL. Rapid recovery from major depression using magnesium treatment. Med Hypotheses. 2006;67(2):362-70. Epub 2006 Mar 20. PubMed

Omega-3 Fatty Acids

Omega-3 fatty acids are a type of good fat needed for normal brain function. Omega-3 fatty acids are found in fish oil and certain plants. They're being studied as a possible mood stabilizer for people with bipolar depression and other psychiatric disorders. Fish oil capsules containing omega-3 fatty acids are sold in stores. Another way to get more omega-3 fatty acids is simply to eat more fish, tofu, soybeans, walnuts, or canola or flaxseed oil.

Studies have linked depression with low dietary intake of omega-3 fatty acids. In countries with higher fish consumption, such as Japan and Taiwan, the depression rate is 10 times lower than in North American. Postpartum depression is also less common.

Scientific evidence of Omega-3 Fatty Acids effectiveness

• 1. Lin PY, Su KP. A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids. J Clin Psychiatry. 2007 Jul;68(7):1056-61. PubMed
• 2. Hallahan B, Hibbeln JR, Davis JM, Garland MR. Omega-3 fatty acid supplementation in patients with recurrent self-harm. Single-centre double-blind randomised controlled trial. Br J Psychiatry. 2007 Feb;190:118-22. PubMed
• 3. Mamalakis G, Kiriakakis M, Tsibinos G, Hatzis C, Flouri S, Mantzoros C, Kafatos A. Depression and serum adiponectin and adipose omega-3 and omega-6 fatty acids in adolescents. Pharmacol Biochem Behav. 2006 Oct;85(2):474-9. Epub 2006 Nov 28. PubMed
• 4. Nemets H, Nemets B, Apter A, Bracha Z, Belmaker RH. Omega-3 treatment of childhood depression: a controlled, double-blind pilot study. Am J Psychiatry. 2006 Jun;163(6):1098-100. PubMed
• 5. Freeman MP, Hibbeln JR, Wisner KL, Brumbach BH, Watchman M, Gelenberg AJ. Randomized dose-ranging pilot trial of omega-3 fatty acids for postpartum depression. Acta Psychiatr Scand. 2006 Jan;113(1):31-5. PubMed