What are natural treatments for mild to moderate depression?

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Treatment of mild to moderate emotional illness.
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Introduction

Depression is a common emotional illness that varies widely in its intensity. Many of the natural treatments described in this section have been evaluated in people with major depression of mild to moderate intensity. This apparently contradictory language indicates a level of clinical depression that is significantly more intense than simply feeling “blue,” but it is not as disabling as major depression of severe intensity, which usually requires hospitalization.

Typical symptoms of major depression of mild to moderate severity include depressed mood, lack of energy, sleep problems, anxiety, appetite disturbance, difficulty concentrating, and poor stress tolerance. Irritability can also be a sign of depression.

More severe depression includes markedly depressed mood complicated by symptoms such as slowed speech, slowed (or agitated) responses, markedly impaired memory and concentration, excessive (or diminished) sleep, significant weight loss (or weight gain), intense feelings of worthlessness and guilt, recurrent thoughts of suicide, and lack of interest in pleasurable activities. This form of clinical depression is a dangerous and excruciating illness. The emotional structure of the brain has frozen into a pattern of misery that cannot be altered by willpower, a change of scenery, or the most earnest efforts of friends.

One of the earliest successful treatments for major depression was shock therapy. This technique is in some ways analogous to rebooting a computer, and in cases of major depression, its effects were revolutionary. For the first time, a reliable way was available to help people with severe major depression.

However, shock treatment was overused at first and became unpopular as a result of this overuse; ethical concerns over this type of treatment also arose. The accidental discovery of antidepressant drugs provided a route with fewer interventions. The original antidepressants, known as monoamine oxidase inhibitors (MAOIs), could be used with major depression as successfully as shock treatment. However, MAOIs can cause serious and even fatal side effects.

Subsequently, antidepressants with progressively fewer side effects came on the market, but most of them still caused significant fatigue. Because fatigue is one of the most characteristic symptoms of mild to moderate depression, such medications were seldom found useful for anything other than severe depression. With the appearance of the selective serotonin reuptake inhibitor (SSRI) class of antidepressants, however, there was a practical option for depression that was less than catastrophic. In no time, enormous numbers of people began taking Prozac and similar drugs for mild to moderate depression and for the related, but more mild, condition known as dysthymia.

The big advantage of the SSRIs is that they usually do not cause severe fatigue. Many people find them to be entirely free of side effects. However, side effects are not uncommon and include sexual disturbances (such as impotence in men and, in women, the loss of the ability to experience an orgasm), insomnia, and nervousness. The antidepressant drug Wellbutrin is an option for people who have sexual side effects from SSRIs.

Principal Proposed Natural Treatments

Alternative medicine offers numerous options for treating depression, but only one has strong scientific evidence behind it: the herb St. John’s wort.

St. John’s wort. Numerous double-blind, placebo-controlled studies have examined the effectiveness of St. John’s wort for the treatment of mild to moderate major depression, and most have found the herb more effective than placebo. In addition, several studies have found that St. John’s wort is at least as effective as standard antidepressants, including fluoxetine (Prozac), sertraline (Zoloft), citalopram (Celexa), and paroxetine (Paxil).

A 2008 detailed review of twenty-nine randomized, placebo-controlled trials found that St. John’s wort was consistently more effective than placebo and just as effective as standard antidepressants. The total number of persons in these trials runs into the several thousands and compares favorably to the evidence base for approved drugs. St. John’s wort has also shown some promise for severe major depression, but the evidence is quite limited. St. John’s wort alone should never be relied on for the treatment of severe depression.

Much has been made of two double-blind, placebo-controlled trials performed in the United States that failed to find St. John’s wort more effective than placebo for mild to moderate depression. However, two studies cannot overturn a body of positive research. Approximately 35 percent of double-blind studies involving pharmaceutical antidepressants have also failed to find the active agent significantly more effective than placebo. As if to illustrate this, in the more recent of the two trials in which St. John’s wort failed to prove effective, the drug Zoloft also failed to prove effective. The reason for these negative outcomes is not that Zoloft (or any other drug) does not work. Rather, statistical effects can easily hide the benefits of a drug, especially in a condition like depression in which there is a high placebo effect and no truly precise method for measuring symptoms.

St. John’s wort seldom causes immediate side effects. However, it interacts adversely with many critical medications and may present other safety issues.

Other Proposed Natural Treatments

There are many other herbs and supplements that may be helpful in depression, although the evidence for them is not as strong as that for St. John’s wort.

Folate. In the body, the vitamin folate works in tandem with the supplement S-adenosylmethionine. Observational studies have suggested that depressed people have reduced folate levels, and some evidence hints that folate supplements may help alleviate depression. In addition, people with particularly low folate levels may respond poorly to antidepressants.

Based on these findings, a study examined the effects of combining folate with antidepressant treatment. This ten-week, double-blind, placebo-controlled trial of 127 people with severe major depression found that folate supplements at a dose of 500 micrograms daily significantly improved the effectiveness of Prozac in female participants. Improvement in male participants was not significant, but blood tests conducted during the study suggest that higher intake of folate might be necessary for men.

S-adenosylmethionine. The supplement S-adenosylmethionine (SAMe) has been widely marketed for the treatment of depression, but the evidence to indicate that it works remains incomplete. Several double-blind, placebo-controlled studies have found SAMe effective in relieving depression; however, most of these studies were small and poorly reported. In addition, many used injected SAMe rather than the oral supplement. Furthermore, the most recent and best-designed of these, a double-blind, placebo-controlled study of 133 depressed people, actually failed to find intravenous SAMe more effective than placebo.

In addition to placebo-controlled studies, several trials have compared SAMe with antidepressant drugs in the tricyclic family. Again, many of these studies were poorly reported and designed, or they used injected SAMe rather than the oral supplement. Of the studies using oral SAMe, the best was a six-week double-blind trial of 281 people with mild depression. The results showed that SAMe was about as effective as the drug imipramine. However, the lack of a placebo group in this trial makes the results less than fully reliable.

Other small studies have also compared the benefits of oral or intravenous SAMe to those of tricyclic antidepressants and have found generally equivalent results, although, again, poor reporting and inadequacies of study design (such as too limited a treatment interval) mar the meaningfulness of the outcomes.

Ginkgo biloba. The herb Ginkgo biloba is used mainly for age-related mental decline such as that from Alzheimer’s disease. However, during the studies on impaired mental function, researchers frequently observed improvements in mood and relief from symptoms of depression. This incidental discovery led scientists to investigate whether ginkgo might be useful as an antidepressant treatment.

One double-blind study, published in 1990, evaluated this effect in sixty people who had depressive symptoms and signs of dementia. The results showed significant improvements among participants given ginkgo extract instead of placebo.

Another study followed forty depressed people older than age fifty years who had not responded successfully to antidepressant treatment. Those who were given ginkgo showed an average drop of 50 percent in scores on the Hamilton Depression scale, whereas the placebo group showed only a 10 percent improvement.

In 1994, research was reported that may shed light on the mechanism by which ginkgo may reduce depression. This study examined levels of serotonin receptors in rats of various ages. When older rats were given ginkgo, the level of serotonin-binding sites increased. However, the same effect was not observed in younger rats. The researchers theorized that ginkgo may block an age-related loss of serotonin receptors. Reduced receptors for serotonin may mean that the body needs more serotonin to produce a normal effect. Thus, ginkgo might improve the brain’s ability to respond to serotonin (in older people). However, this is still highly speculative.

Phenylalanine. Phenylalanine is a naturally occurring amino acid that is consumed in daily diets. There is some evidence that phenylalanine supplements may help reduce symptoms of depression.

Phenylalanine occurs in right-hand and left-hand forms, known as D-phenylalanine and L-phenylalanine, respectively. Some studies have evaluated the D form and others have evaluated a mixture of the D and L forms. Both formulations may provide some measure of relief for symptoms of depression. The mixed form (DLPA) is the one most commonly available in stores.

A 1978 study compared the effectiveness of D-phenylalanine with the antidepressant drug imipramine (taken in daily doses of 100 mg) and found them to be equally effective. A total of sixty people were randomly assigned to either one group or the other and followed for thirty days. D-phenylalanine worked more rapidly, producing significant improvement in only fifteen days.

Another double-blind study followed twenty-seven people, one-half of whom received DL-phenylalanine and the other half imipramine in higher doses of 150 to 200 mg daily. When the participants were reevaluated in thirty days, the two groups had improved by the same amount.

It seems that no properly designed studies comparing phenylalanine to placebo have been conducted. Until these studies are performed, phenylalanine cannot be considered a proven treatment for depression, but it is certainly promising.

5-hydroxytryptophan. When the body manufactures serotonin, it first makes 5-hydroxytryptophan (5-HTP). The theory behind taking 5-HTP as a supplement is that providing the one-step-removed raw ingredient might raise serotonin levels.

There have been several preliminary studies of 5-HTP. The best of these trials was a six-week study of sixty-three people given either 5-HTP (100 mg three times daily) or an antidepressant in the Prozac family (50 mg three times daily). The results showed equal benefit between the supplement and the drug. Actually, 5-HTP worked a little better, but from a mathematical perspective, the difference was not statistically significant. 5-HTP caused fewer and less severe side effects than the drugs in the Prozac family. The only real complaint was occasional mild digestive distress.

Fish oil. It has been suggested that fish oil or the related substance ethyl-EPA (eicosapentaenoic acid) may be helpful for people with depression. For example, a four-week, double-blind, placebo-controlled trial evaluated the potential benefits of fish oil in twenty persons with depression. All but one of the participants were also taking standard antidepressants and had been for a minimum of three months. By week three of the trial, the level of depression had improved to a significantly greater extent in the fish oil group than in placebo group. In addition, a double-blind, placebo-controlled study of seventy people with depression who did not respond well to drug treatment found that the addition of ethyl-EPA (a modified form of a primary ingredient of fish oil) improved the response. Similarly, a double-blind study that evaluated the antidepressant effect of EPA plus fluoxetine found the combination to be more effective than fluoxetine or EPA alone after four weeks of treatment.

In another study, forty people who had committed repeated acts of self-harm were given either fish oil or placebo for twelve weeks. The results indicated that fish oil supplementation markedly reduced measures of suicidal ideation and improved well-being. However, the best and most recent studies have failed to find benefit.

A meta-analysis (formal statistical review of evidence) published in 2007 failed to find convincing evidence of benefit. The largest (seventy-seven participants) study in this review failed to find fish oil more effective than placebo for treatment of depression. Two subsequent studies enrolling almost three hundred people also failed to find benefit. A third placebo-controlled study found no benefit for fish oil in improving “mental well-being” among 320 older adults without a diagnosis of depression.

Exercise. Exercise may be helpful for depression. In a review published in the journal Sports Medicine, researchers analyzed the published research on this subject and concluded that exercise does help. In seven of eight studies reviewed, various forms of exercise proved beneficial for depression. Aerobic exercise, weight training, dancing, and racquetball all produced improvements in mood compared to no exercise.

However, the findings of the one negative study reported in this review cast doubt on the other studies. In this trial, some participants exercised while others took a course at a school and did not exercise. The results: Equal benefits were seen in both groups. This suggests that it may not be the exercise itself that is helping, but rather the general effects of participation in an organized activity.

Another feature of the positive studies also tends to cast doubt on the value of exercise per se in depression. One might think that if it were exercise itself improving mood, the more effectively the participants exercised, the greater the effect. However, no correlation was seen between how much participants increased their physical fitness and how significantly their depression improved.

Repetitive transcranial magnetic stimulation. Repetitive transcranial magnetic stimulation (rTMS) involves the application of low-frequency magnetic pulses to the brain. A growing body of evidence suggests, on balance, that rTMS may be helpful for depression.

In a well-designed trial, for example, seventy people with major depression were given rTMS or sham rTMS in a double-blind setting for two weeks. The results showed that participants who had received actual treatment experienced significantly greater improvement than those receiving sham treatment.

In another trial involving ninety-two older persons whose depression had been linked to poor blood flow to the brain (vascular depression), actual rTMS was significantly more effective than a sham rTMS. Benefits were more notable in younger persons.

In a particularly persuasive piece of evidence, researchers pooled the results of thirty double-blind trials involving 1,164 depressed persons and determined that real rTMS is significantly more effective than sham rTMS.

Two separate studies suggest that rTMS may be an effective additional treatment for the 20 to 30 percent of depressed people for whom conventional drug therapy is not successful. Another group of researchers pooled the results of twenty-four studies involving 1,092 persons and found rTMS to be more effective than sham for treatment-resistant depression. ECT (electroconvulsive therapy, or shock treatment) is often used for people who fall in this category, but rTMS may be an equally effective and less traumatic alternative.

Other herbs and supplements. Like ginkgo, the supplement phosphatidylserine is used mainly for mental decline in the elderly, but it may also offer antidepressant benefits. Limited evidence hints that acetyl-L-carnitine may also offer benefits for the elderly and, potentially, for younger people.

Diets low in vitamin B6 or vitamin B12 have been associated with symptoms of depression. While there is little direct evidence that taking these supplements can help depression, deficiencies of vitamin B6 are common and vitamin B12 deficiencies occur more often with advancing age, so it may be a good idea to take these vitamins on general principles. Nonetheless, a randomized trial involving 299 men older than age seventy-five years found that a daily supplement containing a combination of vitamins B6, B12, and folate was no better than placebo at preventing depression in a two-year period.

Other micronutrients are also commonly deficient in the elderly. A small study among nursing home residents found that low levels of the mineral selenium was associated with depression. Moreover, eight weeks of mineral supplementation tended to improve the mood of the most seriously depressed persons with low selenium levels.

In a small, double-blind, placebo-controlled study, tincture of lavender enhanced the antidepressant effectiveness of the drug imipramine. Also, the hormone dehydroepiandrosterone has shown some promise for depression.

When depression is characterized by rapid mood changes, excessive sleeping and eating, a sense of leaden paralysis, and extreme sensitivity to negative life events, the condition is called atypical depression. A small (fifteen participants), double-blind, placebo-controlled study found that chromium picolinate might be helpful for this form of depression; however, a much larger study failed to find convincing benefits. One study found weak evidence that zinc supplements may enhance the effectiveness of standard antidepressants.

According to five preliminary double-blind studies, the use of the herb saffron (Crocus sativus) at 30 mg daily is more effective than placebo and just as effective as standard treatment for major depression. However, all these studies were small and were performed by a single research group in Iran. Larger studies and independent confirmation will be necessary to determine whether saffron truly is effective for depression. Two studies of somewhat questionable validity reported benefit with an herbal combination used in traditional Chinese herbal medicine (Free and Easy Wanderer Plus).

Beta-carotene, damiana, nicotinamide adenine dinucleotide, pregnenolone, and tyrosine are also sometimes recommended for depression, but there is no meaningful evidence that they work. Also, a double-blind study of forty-two people with severe depression found no improvement with the supplement inositol. Similarly, the use of multivitamin mixtures has failed to prove more effective than placebo.

Alternative therapies. Ayurveda, hatha yoga, massage, and relaxation therapies have all been studied for their effectiveness against depression, but results have been largely unconvincing. Studies on acupuncture as a treatment for depression have shown mixed results. In a review of twenty trials involving two thousand persons with major depression, researchers concluded that real acupuncture’s effectiveness was comparable to that of antidepressants but was no more effective than sham acupuncture for this population. Other studies have not found this benefit, though. There is some suggestion that combining acupuncture with fluoxetine (Prozac) may hasten the effect of the antidepressants and allow for a lower dose.

Herbs and Supplements to Use Only with Caution

Various herbs and supplements may interact adversely with drugs used to treat depression.

Bibliography

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Butler, L. D., et al. “Meditation with Yoga, Group Therapy with Hypnosis, and Psychoeducation for Long-Term Depressed Mood.” Journal of Clinical Psychology 64 (2008): 806-820.

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Ford, A. H., et al. “Vitamins B12, B6, and Folic Acid for Onset of Depressive Symptoms in Older Men.” Journal of Clinical Psychiatry 69 (2008): 1203-1209.

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Hallahan, B., et al. “Omega-3 Fatty Acid Supplementation in Patients with Recurrent Self-Harm.” British Journal of Psychiatry 190 (2007): 118-122.

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Zhang, Z. J., et al. “The Effectiveness and Safety of Acupuncture Therapy in Depressive Disorders.” Journal of Affective Disorders 124 (2010): 9-21.

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