Natural Treatments for Mild to Moderate Depression

• PRINCIPAL PROPOSED NATURAL TREATMENTS: Repetitive transcranial magnetic stimulation, St. John’s wort, exercise, hatha yoga
• OTHER PROPOSED NATURAL TREATMENTS: Acetyl-L-carnitine, acupuncture, Ayurveda, beta-carotene, chromium, damiana, dehydroepiandrosterone, fish oil, 5-hydroxytryptophan, folate, ginkgo, inositol, lavender, massage, multivitamins, nicotinamide adenine dinucleotide, phenylalanine, phosphatidylserine, pregnenolone, S-adenosylmethionine, saffron (Crocus sativus), traditional Chinese herbal medicine, tyrosine, vitamin B6, vitamin B12, zinc

DEFINITION: Treatment of mild to moderate mood disorder

Introduction

Depression is a common mood disorder that varies widely in intensity. Many of the natural treatments described in this section have been evaluated in people with major depression of mild to moderate intensity. This contradictory language indicates a level of clinical depression that is significantly more intense than simply feeling “blue.” However, it is not as disabling as major depression of severe intensity, which can require in-patient treatment.

Typical symptoms of major depression of mild to moderate severity include depressed mood, lack of energy, sleep problems, feelings of sadness or anxiety, a sense of hopelessness or worthlessness, appetite disturbances, 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 gain, intense feelings of worthlessness and guilt, recurrent thoughts of suicide, and a lack of interest in and a loss of enjoyment in pleasurable activities. This form of clinical depression is a dangerous and excruciating illness.

One of the earliest successful treatments for major depression was shock therapy. This technique is in some ways analogous to rebooting a computer. In cases of major depression, its effects were revolutionary. For the first time, a reliable medical treatment 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 as ethical concerns over the treatment also arose. The accidental discovery of antidepressant drugs provided a route with fewer interventions. The original antidepressants were known as monoamine oxidase inhibitors (MAOIs) and 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 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. 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 SSRIs is that they usually do not cause severe fatigue. Many people find them to have few side effects. However, side effects are not uncommon and include sexual disturbancessuch as impotence in men and, in women, the loss of the ability to experience an orgasminsomnia, dry mouth, nausea, and nervousness. The antidepressant drug Wellbutrin was developed as an option for people who experienced sexual side effects from SSRIs.

Principal Proposed Natural Treatments

Alternative medicine offers numerous options for treating depression. However, only one has strong scientific evidence behind itthe 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. However, preparations of St. John’s wort are not regulated by the US Food and Drug Administration, leading to variations in dosage and formulation. St. John’s wort can also cause serious drug interactions, particularly with oral contraceptives and antiretrovirals. For these reasons, the American Psychiatric Association and the National Institute for Health and Care Excellence recommend against the routine use of St. John’s wort for the treatment of depression.

A comprehensive medical review published in 2022 showed that St. John's wort works better than a placebo and works about as well as regular antidepressant medications for treating mild to moderate depression. Some research even found it worked better than common antidepressants like fluoxetine, though most studies showed they work equally well. The herb is especially popular in Germany, where doctors regularly prescribe it for depression. However, doctors recommend against using St. John's wort for severe depression, and we still need more research to know if it keeps working effectively over long periods of time.

Much was 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 thirty-five 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. Individuals taking SSRIs should not take St. John's wort at the same time because it can increase the risk of developing serotonin syndrome. This syndrome is a toxic reaction brought on by too much serotonin activity. The condition requires immediate medical attention, with symptoms including anxiety, restlessness, confusion, weakness, tremors, muscle twitching or spasms, profuse sweating, and rapid heartbeat. In severe cases, life-threatening fever, arrhythmia, loss of consciousness, or seizure can occur.

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-adenosyl-methionine. Observational studies have suggested that people with depression 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 a higher intake of folate might be necessary for men.

A 2014 trial involving 475 patients with moderate to severe depression, most of whom were on SSRIs, found no statistically significant differences among those who received 5-milligram folate supplements daily for three months and those who received a placebo. The treatment and placebo were compared for symptom severity, suicidality, and mental or physical health.

S-adenosyl-methionine. The supplement S-adenosyl-methionine (SAMe) has been widely marketed for the treatment of depression, but the evidence to indicate that it works is modest at best and limited by a lack of clinical support and experience. Several double-blind, placebo-controlled studies have found SAMe effective in relieving depression. However, most of these studies were small and poorly reported and 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 designsuch as too limited a treatment intervalmar 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 who were given ginkgo extract instead of a placebo.

Another study followed forty people older than age fifty years with depression 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.

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.

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 at 100 milligrams (mg) three times daily, or an antidepressant in the Prozac family at 50 mg three times daily. The results showed equal benefits 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.

Based on the latest knowledge about how it works, there is modest evidence that 5-HTP is effective, but it should not be taken with SSRIs, as it might increase the risk of serotonin syndrome.

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 the 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 a 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 benefits.

A meta-analysis failed to find convincing evidence of benefit. The largest study in this review had seventy-seven participants and was unable to find fish oil more effective than a placebo for the treatment of depression. Two subsequent studies that enrolled almost three hundred people also failed to find any benefits. 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 has been found to be helpful for the treatment of depression. In a review published in the journal Sports Medicine, researchers analyzed the published research on this subject and concluded that exercise is beneficial. 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. Exercise has been found to be comparable to antidepressant medications as a first-line treatment for mild to moderate depression. Physical activity has also been shown to improve depressive symptoms when used as an adjunct to antidepressants.

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 result was equal benefits 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.

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 older adults, but it may also offer antidepressant benefits. Limited evidence hints that acetyl-L-carnitine may also offer benefits for older people 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 a placebo at preventing depression in a two-year period.

Other micronutrients are also commonly deficient in older people. A small study among nursing home residents found that low levels of the mineral selenium were 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.

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 failed to prove more effective than placebo.

Alternative therapies.Ayurveda, hatha yoga, massage, mindfulness, and relaxation therapies have all been studied for their effectiveness against depression. Yoga, which combines physical postures, controlled breathing, and meditation, appears to be associated with short term improvements in depression and may be used in conjunction with other treatments to manage mild to moderate depression. 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. Some research suggests combining acupuncture with fluoxetine (Prozac) may hasten the effect of the antidepressants and allow for a lower dose. A systematic review of seventeen poor- to moderate-quality trials found massage therapy to be associated with reduced depressive symptoms. Several studies have found mindfulness-based interventions to decrease symptom severity in patients with a current episode of depression and to delay relapse in patients with recurrent depression who were not currently experiencing an acute episode. Daily light therapy has also been found to be beneficial in the treatment of seasonal affective disorder, which causes depressive symptoms.

A study published in 2021 found natural products were effective in treating stress-induced depression. Researchers found fifty-eight bioactive phytochemical compounds, fifty-six herb medicines, and five formulas from traditional Chinese medicine helped alleviate this type of depression by inhibiting monoamine oxidase (MAO reaction). Natural products have also been vital as a promising source for future antidepressant drug discovery.

Herbs and Supplements to Use Only with Caution

Various herbs and supplements may interact adversely with SSRIs and other drugs used to treat depression. Consult with your doctor prior to taking any herb or supplement for the treatment of depression.

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