Depression

Depression, characterized by unhappy feelings of hopelessness, can be a response to stressful events, hormonal imbalances, biochemical abnormalities, or other causes. Mild depression that passes quickly may not require any diagnosis or treatment. However, when depression becomes recurrent, constant, or severe, it should be diagnosed by a licensed counselor, psychologist, social worker, or psychiatrist. Diagnosis may be crucial for determining appropriate treatment. For example, depression caused by low thyroid function can be successfully treated with prescription thyroid medication. Suicidal depression often requires prescription antidepressants. Persistent mild-to-moderate depression triggered by stressful events is often best treated with counseling and not necessarily with medications.

When depression is not a function of external events, it is called endogenous. Endogenous depression can be due to biochemical abnormalities. Lifestyle changes and herbs may be used with people whose depression results from a variety of causes, but dietary and nutrient interventions are usually best geared to endogenous depression.

Checklist for Depression

Rating Nutritional Supplements Herbs
3Stars Folic acid (for folate deficiency)
Iron (for iron deficiency)
Vitamin B12 (for B12 deficiency)
Vitamin B6 (with oral contraceptives)		  
2Stars 5-HTP
Acetyl-L-carnitine (for elderly people)
DHEA (this supplement requires supervision by a healthcare professional)
Fish oil (EPA/DHA)
Inositol
L-phenylalanine/DLPA
L-tyrosine
Melatonin
SAMe
Selenium
Vitamin B6 (for premenstrual syndrome)
Vitamin D		 Ginkgo biloba (for elderly people)
St. John’s wort
1Star Calcium
Chromium
NADH
Phosphatidylserine		 Damiana
Pumpkin
Vervain
Yohimbe
See also:  Homeopathic Remedies for Depression
3Stars Reliable and relatively consistent scientific data showing a substantial health benefit.
2Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.
1Star An herb is primarily supported by traditional use, or the herb or supplement has little scientific support and/or minimal health benefit.

What are the symptoms of depression? A diagnosis of depression requires at least five of the following symptoms.

  • Depressed mood.
  • Diminished interest or pleasure in all or most activities, most of the day, nearly every day.
  • Significant weight loss or gain when not dieting (e.g., more than 5% of body weight in a month).
  • Insomnia or excessive sleeping nearly every day.
  • Agitation or depression in voluntary muscle movements nearly every day.
  • Fatigue or loss of energy nearly every day; feelings of worthlessness or excessive and inappropriate guilt nearly every day.
  • Diminished ability to think or concentrate, or indecisiveness nearly every day.
  • Recurrent thoughts of death (not just fear of death), recurrent suicidal ideation without a plan, or a suicide attempt or specific plan to commit suicide.

How is it treated? Psychotherapy and drug therapy are the mainstays of conventional therapy for depression. Drugs that may be prescribed include selective serotonin reuptake inhibitors, such as fluoxetine (Prozac®), paroxetine (Paxil®), sertraline (Zoloft®), and others; MAO inhibitors, such as isocarboxazid (Marplan®), phenelzine (Nardil®), tranylcypromine (Parnate®), and others; tricyclic antidepressants, such as amitriptyline (Elavil®), imipramine (Tofranil), doxepin (Sinequan®), and others; and heterocyclic antidepressants, such as trazodone (Desyrel®), maprotiline (Ludiomil®), bupropion (Wellbutrin®), and others.

Dietary changes that may be helpful: Although some research has produced mixed results,1 double-blind trials have shown that food allergies can trigger mental symptoms, including depression.2 3 People with depression who do not respond to other natural or conventional approaches should consult a doctor to diagnose possible food sensitivities and avoid offending foods.

Restricting sugar and caffeine in people with depression has been reported to elevate mood in preliminary research.4 How much of this effect resulted from sugar and how much from caffeine remains unknown. Researchers have reported that psychiatric patients who are heavy coffee drinkers are more likely to be depressed than other such patients.5 However, it remains unclear whether caffeine can cause depression or whether depressed people were more likely to want the “lift” associated with drinking a cup of coffee. In fact, “improvement in mood” is considered an effect of long-term coffee consumption by some researchers, a concept supported by the fact that people who drink coffee have been reported to have a 58–66% decreased risk of committing suicide compared with non-coffee drinkers.6 Nonetheless, a symptom of caffeine addiction can be depression.7 Thus, consumption of caffeine (mostly from coffee) has paradoxically been linked with both improvement in mood and depression by different researchers. People with depression may want to avoid caffeine as well as sugar for one week to see how it affects their mood.

There is evidence that people with major depression may have insensitivity to insulin and impaired glucose tolerance.8 Whether treatment of impaired glucose tolerance helps depression is unknown, but a doctor can order laboratory tests to detect such abnormalities, and initiate treatment as appropriate.

The amount and type of dietary fat consumed may influence the incidence of depression. Previous studies have found that diet regimens designed to lower cholesterol levels may reduce death from cardiovascular disease, but may also heighten the incidence of depression.9 Does low cholesterol cause depression? It appears not, since studies have shown no adverse effect on mood in people taking cholesterol-lowering drugs.10 11 The connection more likely has to do with the balance of fats in the diet. Diets to lower blood cholesterol usually focus on restricting total fat intake while increasing the intake of polyunsaturated fats (e.g., corn and soybean oils). These oils are very high in omega-6 fatty acids, but the recommended diets otherwise lack important omega-3 fatty acids (EPA and DHA). A high intake of omega-6 fatty acids relative to omega-3 fatty acids and an inadequate intake of omega-3 fatty acids (e.g., from fish and fish oils) have been associated with increased levels of depression.12 People who eat diets high in omega-3 fatty acids from fish have a lower incidence of depression and suicide.13 14 15 16 There is one case report of a man with a long history of severe depression who showed clear improvement within one month of starting a purified EPA supplement (4 grams per day of the ethyl ester of eicosapentaenoic acid).17

Lifestyle changes that may be helpful: Exercise increases the body’s production of endorphins—chemical substances that can relieve depression. Scientific research shows that routine exercise can positively affect mood and help with depression.18 As little as three hours per week of aerobic exercise can profoundly reduce the level of depression.19 One trial compared the effects of an exercise training program with those of a prescription antidepressant drug in people over 50 years of age.20 The researchers found the two approaches to be equally effective after 16 weeks of treatment.

Nutritional supplements that may be helpful: Iron deficiency is known to affect mood and can exacerbate depression, but it can only be diagnosed and treated by a doctor. While iron deficiency is easy to fix with iron supplements, people who have not been diagnosed with iron deficiency should not supplement iron.

Deficiency of vitamin B12 can create disturbances in mood that respond to B12 supplementation.21 Significant vitamin B12 deficiency is associated with a doubled risk of severe depression, according to a study of physically disabled older women.22 Depression caused by vitamin B12 deficiency can occur even if there is no B12 deficiency-related anemia.23

Mood has been reported to sometimes improve with high amounts of vitamin B12 (given by injection), even in the absence of a B12 deficiency.24 Supplying the body with high amounts of vitamin B12 can only be done by injection. However, in the case of overcoming a diagnosed B12 deficiency, one can follow an initial injection with oral maintenance supplementation (1 mg per day), even when the cause of the deficiency is a malabsorption problem such as pernicious anemia.

A deficiency of the B vitamin folic acid can also disturb mood. A large percentage of depressed people have low folic acid levels.25 Folic acid supplements appear to improve the effects of lithium in treating manic-depressives.26 Depressed alcoholics report feeling better with large amounts of a modified form of folic acid.27 Anyone suffering from chronic depression should be evaluated for possible folic acid deficiency by a doctor. Those with abnormally low levels of folic acid are sometimes given short-term, high amounts of folic acid (10 mg per day).

Preliminary evidence indicates that people with depression may have lower levels of inositol.28 Supplementation with large amounts of inositol can increase the body’s stores by as much as 70%.29 In a double-blind trial, depressed people who received 12 grams of inositol per day for four weeks had a significant improvement in symptoms compared to those who took placebo.30 In a double-blind follow-up to this trial, the antidepressant effects of inositol were replicated. Half of those who responded to inositol supplementation relapsed rapidly when inositol was discontinued.31

Oral contraceptives can deplete the body of vitamin B6, a nutrient needed for maintenance of normal mental functioning. Double-blind research shows that women who are depressed and who have become depleted of vitamin B6 while taking oral contraceptives typically respond to vitamin B6 supplementation.32 In one trial, 20 mg of vitamin B6 were taken twice per day. Some evidence suggests that people who are depressed—even when not taking the oral contraceptive—are still more likely to be B6 deficient than people who are not depressed.33

Several clinical trials also indicate that vitamin B6 supplementation helps alleviate depression associated with premenstrual syndrome (PMS),34 although the research remains inconsistent.35 Many doctors suggest that women who have depression associated with PMS take 100–300 mg of vitamin B6 per day—a level of intake that requires supervision by a doctor.

Less than optimal intake of selenium may have adverse effects on psychological function, even in the absence of signs of frank selenium deficiency. In a preliminary trial of healthy young men, consumption of a high-selenium diet (226.5 mcg selenium per day) was associated with improved mood (i.e., decreased confusion, depression, anxiety, and uncertainty), compared to consumption of a low-selenium diet (62.6 mcg selenium per day.)36 In a double-blind trial, people who had a low selenium intake experienced greater improvement in depression symptoms after selenium supplementation (100 mcg per day) than did people with adequate selenium intake, suggesting that low-level selenium deficiency may contribute to depression.37

Vitamin D supplementation may be associated with elevations in mood. In a double-blind trial, healthy people were given 400–800 IU per day of vitamin D3, or no vitamin D3, for five days during late winter. Results showed that vitamin D3 significantly enhanced positive mood and there was some evidence of a reduction in negative mood compared to a placebo.38 In another double-blind trial, people without depression took 600 IU of vitamin D along with 1,000 mg of calcium, or a placebo, twice daily for four weeks.39 Compared to the placebo, combined vitamin D and calcium supplementation produced significant elevations in mood that persisted at least one week after supplementation was discontinued.

Omega-3 fatty acids found in fish oil, particularly DHA, are needed for normal nervous system function. Depressed people have been reported to have lower omega-3 fatty acid levels (e.g., DHA) than people who are not depressed.40 41 42 43 Low levels of the other omega-3 fatty acid from fish, EPA, have correlated with increased severity of depression.44 In a double-blind trial, people with manic depression were given a very high intake of supplemental omega-3 fatty acids (enough fish oil to contain 9.6 grams of omega-3 fatty acids per day) for four months.45 Ten of 16 people in the placebo group eventually were forced to discontinue the trial due to worsening depression compared with only 3 of 14 taking omega-3 fatty acids. Some scores of depression levels fell as much as 48% in the omega-3 fatty acids group.

The amino acid, L-tyrosine, can be converted into norepinephrine—a neurotransmitter that affects mood. Women taking oral contraceptives have lower levels of tyrosine, and some researchers think this might be related to depression caused by birth control pills.46 L-tyrosine metabolism may also be abnormal in other depressed people47 and preliminary research suggests supplementation might help.48 49 Several doctors recommend a 12-week trial of L-tyrosine supplementation for people who are depressed. Published research has used a very high amount—100 mg per 2.2 pounds of body weight (or about 7 grams per day for an average adult). It is not known whether such high amounts are necessary to produce an antidepressant effect.

L-Phenylalanine is another amino acid that converts to mood-affecting substances (including phenylethylamine and norepinephrine). Preliminary research reported that L-phenylalanine improved mood in most of the depressed people studied.50 DLPA is a mixture of the essential amino acid L-phenylalanine and its synthetic mirror image, D-phenylalanine. DLPA (or the D- or L- form alone) reduced depression in 31 of 40 people in a preliminary trial.51 Some doctors suggest a one-month trial with 3–4 grams per day of phenylalanine for people with depression, although some researchers have found that even very low amounts—75–200 mg per day—were helpful in preliminary trials.52 In one double-blind trial, depressed people given 150–200 mg of DLPA per day experienced results comparable to that produced by an antidepressant drug.53

Acetyl-L-carnitine may be effective for depression experienced by the elderly. A preliminary trial found that acetyl-L-carnitine supplementation was effective at relieving depression in a group of elderly people, particularly those showing more serious clinical symptoms.54 These results were confirmed in another similar clinical trial.55 In that trial, participants received either 500 mg three times a day of acetyl-L-carnitine or a matching placebo. Those receiving acetyl-L-carnitine experienced significantly reduced symptoms of depression compared to those receiving placebo. At least two other clinical studies of acetyl-L-carnitine for depression in the elderly have reported similar results.56 57 The amount typically used is 500 mg three times daily, although one trial used twice that amount.

Some studies have reported lower DHEA levels in groups of depressed patients.58 However, this finding has not been consistent, and in one trial, severely depressed people were reported to show increases in blood levels of DHEA.59

Despite confusion regarding which depressed people might be DHEA-deficient, most double-blind trials lasting at least six weeks have reported some success in treating people with depression. After six months using 50 mg DHEA per day, “a remarkable increase in perceived physical and psychological well-being” was reported in both men and women in one double-blind trial.60 After only six weeks, taking DHEA in levels up to 90 mg per day led to at least a 50% reduction in depression in five of 11 patients in another double-blind trial.61

Other researchers have reported dramatic reductions in depression at extremely high amounts of DHEA (90–450 mg per day) given for six weeks to adults who first became depressed after age 40 (in men) or at the time of menopause (in women) in a double-blind trial.62 Other double-blind research has shown that limiting supplementation to only two weeks is inadequate in treating people with depression.63 Despite the somewhat dramatic results reported in clinical trials lasting at least six weeks, some experts claim that in clinical practice, DHEA appears to be effective for only a minority of depressed people.64 Moreover, due to fears of potential side effects, most healthcare professionals remain concerned about the use of DHEA. Depressed people considering taking DHEA should consult a doctor well versed in the use of DHEA.

Melatonin might help some people suffering from depression. Preliminary double-blind research suggests that supplementation with small amounts of melatonin (0.125 mg taken twice per day) may reduce winter depression.65 People with major depressive disorders sometimes have sleep disturbances. A timed-release preparation of melatonin (5–10 mg per day for four weeks) was shown to be effective at improving the quality of sleep in people with major depression who were taking fluoxetine (Prozac®), but melatonin did not enhance its antidepressant effect.66 There is a possibility that melatonin could exacerbate depression, so it should only be used for this purpose under a doctor’s supervision.

S-adenosyl methionine (SAMe) is a substance synthesized in the body that has recently been made available as a supplement. SAMe appears to raise levels of dopamine, an important neurotransmitter in mood regulation. Higher SAMe levels in the brain are associated with successful drug treatment of depression, and oral SAMe has been demonstrated to be an effective treatment for depression in most,67 68 69 but not all,70 clinical trials. Most trials used 1,600 mg of SAMe per day. While it does not seem to be as powerful as full applications of antidepressant medications71 or St. John’s wort, SAMe’s effects are felt more rapidly, often within one week.72

Disruptions in emotional well-being, including depression, have been linked to serotonin imbalances in the brain.73 Supplementation with 5-hydroxytryptophan (5-HTP) may increase serotonin synthesis. Researchers are studying the possibility that 5-HTP might help people with depression. Some trials using 5-HTP with people suffering from depression have shown sign of efficacy.74 75 76 77 78 However, much of the research was either uncontrolled or used 5-HTP in combination with antidepressant drugs. Depressed people interested in considering this hormone precursor should consult a doctor.

There have been five case reports of chromium supplementation (200–400 mcg per day) significantly improving mood in people with a type of depression called dysthymic disorder who were also taking the antidepressant drug sertraline (Zoloft®).79 These case reports, while clearly limited and preliminary in scope, warrant further research to better understand the benefits, if any, of chromium supplementation in people with depression.

Phosphatidylserine (PS), a natural substance derived from the amino acid serine, affects the levels of neurotransmitters in the brain related to mood. In a preliminary trial, elderly women suffering from depression who were given 300 mg of PS per day for 30 days experienced, on average, a 70% reduction in the severity of their depression.80

An isolated preliminary trial suggests the supplement NADH may help people with depression.81 Controlled trials are needed, however, before any conclusions can be drawn.

A deficiency of other B vitamins not discussed above (including vitamin B1, vitamin B2, vitamin B3, pantothenic acid and biotin) can also lead to depression. However, the level of deficiency of these nutrients needed to induce depression is rarely found in Western societies.

Are there any side effects or interactions? Refer to the individual supplement for information about any side effects or interactions.

Herbs that may be helpful: St. John’s wort extracts are among the leading medicines used in Germany by medical doctors for the treatment of mild to moderate depression. Using St. John’s wort extract can significantly relieve the symptoms of depression. People taking St. John’s wort show an improvement in mood and ability to carry out their daily routine. Symptoms such as sadness, hopelessness, worthlessness, exhaustion, and poor sleep also decrease.82 83

St. John’s wort extract has been compared to the prescription tricyclic antidepressants, imipramine (Tofranil®),84 85 86 amitriptyline (Elavil®),87 fluoxetine (Prozac®),88 and maprotiline (Ludiomil®).89 The improvement in symptoms of mild to moderate depression was similar, with notably fewer side effects, in people taking St. John’s wort.

In a double-blind trial using standard amounts of fluoxetine (Prozac®)—20 mg per day—St. John’s wort extract in the amount of 400 mg twice daily was equally effective at relieving depression in people aged 60–80 years.90 Another trial found that 250 mg of St. John’s wort extract two times per day was also as effective as 20 mg of fluoxetine in treating adults with mild to moderate depression.91 In both trials comparing St. John’s wort to fluoxetine, there were far fewer side effects reported by people taking St. John’s wort.

One clinical trial compared a higher amount of the St. John’s wort extract LI 160 (1,800 mg per day) with a higher amount of imipramine (150 mg per day) in more severely depressed people.92 Again, the improvement was virtually the same for both groups with far fewer side effects for the St. John’s wort group. While this may point to St. John’s wort as a possible treatment for more severe cases of depression, this treatment should only be pursued under the guidance of a healthcare professional.

Two well-publicized double-blind studies published in the Journal of the American Medical Association (JAMA) concluded that St. John's wort is not an effective treatment for depression. However, each of these studies had potential flaws. In the first study,93 900–1,200 mg of St. John's wort per day was slightly more effective than a placebo, as assessed by the Hamilton Rating Scale for Depression. However, the difference was not statistically significant. Although the remission rate was significantly greater with St. John's wort than with placebo, only 14.3% of the patients who received the herb went into remission, causing the authors of the report to question St. John's wort's efficacy. However, the 4.9% remission rate in the placebo group was far below the placebo response rate seen in other studies of depression. That finding suggests that many of the patients recruited for this study would have been unlikely to respond to any treatment.

In the second JAMA study, depressed patients were given one of three treatments: St. John's wort, placebo, or an antidepressant medication with proven efficacy (e.g., sertraline; Zoloft®). Although St. John's wort was no more effective than the placebo, by many measures neither was sertraline.94 The relatively poor outcome with sertraline makes one wonder whether the design of the study, or the criteria used to select participants, may have somehow skewed the results to make St. John's wort appear less effective than it really is.

Despite these two negative studies, the bulk of the scientific evidence indicates that St. John's wort is an effective treatment for mild to moderate depression.

Recent European trials have successfully treated mild to moderate depression using 500 to 1,050 mg of St. John’s wort per day. As an antidepressant, St. John’s wort should be taken for four to six weeks before judging its effectiveness.

Ginkgo biloba (240 mg per day) may alleviate depression in depressed elderly people not responding to antidepressant drugs.95 It is unknown if ginkgo could alleviate depression in other age groups. A small, preliminary trial has shown that ginkgo can reduce sexual problems caused by antidepressants like fluoxetine (Prozac®), bupropion (Wellbutrin®), venlafaxine (Effexor®), and nefazodone (Serzone®) in men and women.96 Double-blind trials are now needed to determine whether ginkgo is truly effective for this purpose.

Damiana has traditionally been used to treat people with depression. Yohimbine (the active component of the herb yohimbe) inhibits monoamine oxidase (MAO) and therefore may be beneficial in depressive disorders. However, clinical research has not been conducted for its use in treating depression.

Pumpkin seeds contain L-tryptophan, and for this reason have been suggested to help remedy depression.97 However, research is needed before pumpkin seeds can be considered for this purpose. It is unlikely the level of L-tryptophan in pumpkin seeds would be sufficient to relieve depression.

Vervain is a traditional herb for depression; however, there is no research to validate this use.

Are there any side effects or interactions? Refer to the individual herb for information about any side effects or interactions.

Other integrative approaches that may be helpful: Acupuncture may improve depression by affecting the synthesis of neurotransmitters that control mood.98 Controlled trials99 100 101 have found electro-acupuncture (acupuncture accompanied by electrical currents) equally effective as antidepressant drug therapy without causing side effects. However, a controlled trial found that both real and fake acupuncture improved depression equally well compared to no treatment.102 It is well known that placebo effects are common in the treatment of depression,103 so more controlled trials are needed before accepting the usefulness of acupuncture for depression.

Many people who are depressed seek counseling with a psychologist, social worker, psychiatrist, or other form of counselor. An analysis of four properly conducted trials of severely depressed patients comparing the effects of one form of counseling intervention, cognitive behavior therapy, with the effects of antidepressant drugs was published in 1999. In that report, cognitive behavior therapy was at least as effective as drug therapy.104 While the outcome of counseling may be more variable than outcomes from drug or natural substance interventions, many healthcare professionals consider counseling an important part of recovery for depression not due to identifiable biochemical causes.

A rhythmic breathing technique called Sudarshan Kriya Yoga (SKY) may be an effective alternative to antidepressant drugs as an initial treatment for people with clinical depression. In a controlled trial, daily 45-minute SKY sessions six days per week produced a 67% remission rate among people with a diagnosis of depression.105 This effect compared favorably with the effects of electro-shock therapy and the antidepressant drug imipramine; however, no placebo was used in this study. SKY technique is taught by the Art of Living Foundation.

In a controlled trial, magnetic stimulation to the front of the skull and underlying brain produced modest reductions of depressive symptoms in depressed people who had not responded adequately to standard treatment.106 The procedure was performed by psychiatrists using sophisticated electromagnetic medical equipment, not a simple magnet.

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