Sun
19
Apr
Depression (Mild to Moderate)
Depression is a common emotional illness that varies widely in its intensity
from person to person. Many of the natural treatments described in this section
have been evaluated in individuals with major depression of mild to moderate
intensity. (Contrary to widespread misreporting, this is “clinical depression;”
simply not the most severe form of it) This contradictory-sounding language
indicates that the level of depression is more severe than simply feeling
"blue," but it is not as severe as the most intense forms of depression, which
usually require 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.
Severe 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. In a sense, the brain has locked up like a crashed computer. No alternative treatment is especially successful when depression gets this bad.
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 bring people out of the depths of severe major depression. However, shock treatment was overused at first and became unpopular.
The accidental discovery of antidepressant drugs provided a less interventive route.The original antidepressants, known as MAO inhibitors, could bring people out from the depths of major depression as successfully as shock treatment. However, MAO inhibitors can cause serious and even fatal side effects. No one would ever think of using MAO inhibitors to treat mild to moderate depression.
Subsequently, antidepressants with progressively fewer side effects came on the market, but it was not until the appearance of selective serotonin-reuptake inhibitors (SSRIs), such as Prozac and related drugs, that antidepressants became a viable option for depression that was less than catastrophic. Practically overnight, enormous numbers of people began taking Prozac and similar antidepressants for mild to moderate depression.
The big advantage of the SSRIs is that they usually dont cause severe fatigue. Many people find them to be entirely side-effect free. However, side effects are not uncommon and include nausea, insomnia, and sexual disturbances (such as the loss of the ability to experience an orgasm).
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.
Severe 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. In a sense, the brain has locked up like a crashed computer. No alternative treatment is especially successful when depression gets this bad.
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 bring people out of the depths of severe major depression. However, shock treatment was overused at first and became unpopular.
The accidental discovery of antidepressant drugs provided a less interventive route.The original antidepressants, known as MAO inhibitors, could bring people out from the depths of major depression as successfully as shock treatment. However, MAO inhibitors can cause serious and even fatal side effects. No one would ever think of using MAO inhibitors to treat mild to moderate depression.
Subsequently, antidepressants with progressively fewer side effects came on the market, but it was not until the appearance of selective serotonin-reuptake inhibitors (SSRIs), such as Prozac and related drugs, that antidepressants became a viable option for depression that was less than catastrophic. Practically overnight, enormous numbers of people began taking Prozac and similar antidepressants for mild to moderate depression.
The big advantage of the SSRIs is that they usually dont cause severe fatigue. Many people find them to be entirely side-effect free. However, side effects are not uncommon and include nausea, insomnia, and sexual disturbances (such as the loss of the ability to experience an orgasm).
Treatment
Principal Proposed Treatments for Depression (Mild to Moderate):
Alternative medicine offers numerous options for treating depression, but only one has strong scientific evidence behind it: the herb St. Johns wort. The evidence for this herbs effectiveness is nearly as comprehensive as what is required of a drug prior to approval. However, this herb also presents numerous safety risks, including interactions with many drugs. (See the full St. John’s wort article for more information.)
St. Johns Wort
St. Johns wort (Hypericum perforatum)is a common perennial herb, with many branches and bright yellow flowers, that grows wild in much of the world. Its name derives from the herbs tendency to flower around the feast of St. John (wort simply means "plant" in Old English). The species name perforatum derives from the watermarking of translucent dots that can be seen when a leaf of the plant is held up to the sun.
St. Johns wort has a long history of use in emotional disorders. It began to be considered as a treatment for depression early in the twentieth century, and when pharmaceutical antidepressants were invented, German researchers looked for similar properties in St. Johns wort.
Today, St. Johns wort is one of the best-documented herbal treatments, with a scientific record approaching that of many prescription drugs. Indeed, this herb is a prescription antidepressant in Germany. It is covered by that countrys national health-care system and is prescribed more frequently than any synthetic drug.
Research suggests that St. Johns wort is effective in about 55% of cases. As with other antidepressants, the full benefit takes about 4 to 6 weeks to develop. The most common reported effects are brightened mood, increased energy, and improved sleep.
St. Johns wort should never be relied on to treat very severe depression. If you or a loved one is feeling suicidal, unable to cope with daily life, paralyzed by anxiety, incapable of getting out of bed, unable to sleep, or uninterested in eating, see a physician at once. Drug therapy may save your life.
St. Johns wort appears to be reasonably safe when taken alone. However, there is good reason to believe that it may interfere with the effectiveness of numerous medications, including contraceptives, transplant rejection drugs, and treatments for HIV infection.
What Is the Scientific Evidence for St. Johns Wort?
Numerous double-blind placebo-controlled studies enrolling a total of more than 1,000 people have compared St. Johns wort to placebo.
Taken together, the results strongly suggest that St. Johns wort is an effective treatment for mild to moderate depression. Several studies have found that St. Johns wort is equally as effective as standard antidepressants, but causes fewer side effects. For example, four double-blind trials enrolling a total of more than 600 individuals have compared St. John’s wort to either fluoxetine (Prozac) or sertraline (Zoloft). In all these studies, the herb proved at least as effective as the drug, and caused fewer side effects.
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. However, two studies cannot overturn a body of positive research. Approximately 35% 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 sertraline (Zoloft) also failed to prove effective. The reason for these negative outcomes is not that Zoloft (or Prozac, or any other drug) does not work. Rather, statistical effects can easily hide the benefits of a drug, especially in a condition like depression where there is as a high placebo effect and no really precise method or measuring symptoms.
Thus, unless a whole series of studies find St. John’s wort ineffective, especially trials in which a comparison drug treatment does prove effective, St. John’s wort should still be regarded as probably effective for major depression of mild to moderate severity.
For more information, including dosage and safety issues, see the full St. Johns wort article.
Other Proposed Treatments for Depression:
There are a number of other herbs and supplements that may be helpful in depression, although the evidence for them is nowhere near as strong as that for St. Johns wort.
Phenylalanine
Phenylalanine is a naturally occurring amino acid that we all consume in our daily diets. There is some evidence that phenylalanine supplements may help reduce symptoms of depression.
What Is the Scientific Evidence for Phenylalanine?
Phenylalanine occurs in a right-hand and a left-hand form, known as D- 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 against the antidepressant drug imipramine (taken in daily doses of 100 mg) and found them to be equally effective. A total of 60 individuals were randomly assigned to either one group or the other and followed for 30 days. D-phenylalanine worked more rapidly, producing significant improvement in only 15 days.
Another double-blind study followed 27 people, 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 30 days, the two groups had improved by the same amount.
Unfortunately, there do not seem to have been any properly designed studies that compared phenylalanine to placebo. Until these are performed, phenylalanine cannot be considered a proven treatment for depression, but it is certainly promising.
For more information, including dosage and safety issues, see the full phenylalanine article.
5-HTP
A new, up-and-coming treatment for depression is 5-HTP (5-hydroxytryptophan). When the body sets about manufacturing serotonin, it first makes 5-HTP. The theory behind taking 5-HTP as a supplement is that providing the one-step-removed raw ingredient might raise serotonin levels. However, this plausible idea has not been proven.
The amino acid tryptophan used to be recommended as a treatment for depression on the same basis. It is one step back in the chain, being turned by the body into 5-HTP and then to serotonin. However, tryptophan was removed from the market several years ago when a contaminant caused a terrible and often permanent illness in many people who took the supplement. Because 5-HTP is made by a completely different manufacturing process (starting from a plant rather than bacteria), one would not expect the same contaminant to be present. Disturbingly, however, recent reports suggest otherwise.
Like St. Johns wort, 5-HTP is used mainly in Europe, where many physicians find it an effective treatment for both depression and insomnia.
What Is the Scientific Evidence for 5-HTP?
There have been several preliminary studies of 5-HTP. The best of these trials was a 6-week study of 63 people given either 5-HTP (100 mg 3 times daily) or an antidepressant in the Prozac family (fluvoxamine, 50 mg 3 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 fluvoxamine. The only real complaint was occasional mild digestive distress.
For more information, including dosage and safety issues, see the full 5-HTP article.
Ginkgo: Improves Mental Function, but May Help Depression, Too
Ginkgo is used mainly for age-related mental decline such as that from Alzheimers 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 study, published in 1990, evaluated this effect in 60 people who suffered from depressive symptoms along with other signs of dementia. The results showed significant improvements among participants given ginkgo extract instead of placebo.
Another study followed 40 depressed individuals over the age of 50 who had not responded successfully to antidepressant treatment. Those who were given ginkgo showed an average drop of 50% in scores on the Hamilton Depression scale, whereas the placebo group showed only a 10% improvement.
In 1994 an interesting piece of research was reported that may shed light on the mechanism by which ginkgo could 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. Instead of raising the level of serotonin, like Prozac does, ginkgo may thus improve the brains ability to respond to serotonin (at least in older people). However, this is still highly speculative. More experimentation is needed to clarify the mechanism of ginkgos action and to better quantify its effectiveness in depression.
For more information, including dosage and safety issues, see the full ginkgo article.
Phosphatidylserine: Good for Mental Function, May Also Help Depression
Phosphatidylserine is another treatment used mainly for mental decline in the elderly that may also offer antidepressant benefits.
For more information, including dosage and safety issues, see the full phosphatidylserine article.
SAMe
Another European supplement treatment for depression now arrived in the United States is SAMe (S-adenosylmethionine). SAMe is a very important biological molecule that occurs throughout the body. Its job is to hand over a chemical fragment called a methyl group to other chemicals that need it.
The evidence for SAMe as an antidepressant is provocative but far from definitive.
Several double-blind placebo-controlled studies have found SAMe effective in relieving depression, but they were all small and poorly reported, and many used an injected form of the supplement. Furthermore, the most recent trial, a double-blind placebo-controlled study of 133 depressed patients, failed to find intravenous SAMe more effective than placebo. Researchers resorted to questionable statistical manipulation of the data to show benefit.
A recent 6-week double-blind trial of 281 individuals with mild depression compared oral SAMe to imipramine. The results showed that the two treatments were about equally effective.
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.
For more information, including dosage and safety issues, see the full SAMe article.
Folate
In the body, the vitamin folate works in tandem with SAMe. Studies have suggested that depressed individuals have reduced folate levels, and that folate supplements may help alleviate depression. In addition, patients with particularly low folate levels have been found to respond poorly to antidepressants.
Based on these findings, a study examined the effects of combining folate with antidepressant treatment.
This 10-week double-blind placebo-controlled trial of 127 individuals with severe major depression found that folate supplements at a dose of 500 mcg daily significantly improved the effectiveness of fluoxetine (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.
For more information, including dosage and safety issues, see the full folate article.
Exercise
Exercise may be helpful for depression. In a review published in the journal Sports Medicine, authors Tim Meyer and Andreas Broocks analyzed the published research on this subject. Their conclusion: a very qualified "yes."
In seven out of eight studies reviewed, various forms of exercise proved beneficial for depression. Aerobic exercise, weight training, dancing, and racketball all produced improvements in mood as compared to no exercise.
However, the findings of the one negative study reported in this review cast doubt on the others. In this trial, some participants exercised, while others took a course at school and didnt exercise at all. The results: equal benefits 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. Youd 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 signficantly their depression improved.
Other Treatments
A 4-week, double-blind, placebo-controlled trial evaluated the potential benefits of fish oil in 20 indviduals with depression. All but one participant were also taking standard antidepressants and had been taking them for at least 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. Six of 10 participants given fish oil, but only one of 10 given placebo, showed at least a 50% reduction in depression scores by the end of the trial. (A reduction of this magnitude is considered a “cure.”)
A preliminary controlled trial found evidence that acupuncture might be helpful for the treatment of mild depression.
A growing body of small studies suggests that a special form of electromagnetic therapy called transcranial magnetic stimulation (TMS), may be helpful for depression.
Weak evidence suggests that the nutritional substance inositol might be helpful in depression when taken in extremely high doses (12 g daily). However, a double-blind study of 42 people with severe depression that was not responding to standard antidepressant treatment found no improvement when inositol was added. Keep in mind that although this is a nutritional substance, when taken in such enormous doses, its safety cannot be assured.
Preliminary evidence suggests that the substance acetyl-L-carnitine may be useful for depression in the elderly.
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 B6 are common and B12 deficiencies occur more often with advancing age, so it may be a good idea to take these vitamins on general principles.
Intriguing, but highly preliminary, evidence suggests that deficiencies in essential fatty acids may increase the risk of depression; it is possible that fish oil supplements could therefore help prevent depression.
The herbs and supplements beta-carotene, damiana, NADH, pregnenolone, and tyrosine are also sometimes recommended for depression, but there is little evidence as yet that they really work.
Not Recommended Treatments:
The herb yohimbe and the hormone DHEA are sometimes suggested for depression, but because of potential risks we do not suggest using them except under the supervision of a qualified health-care professional (if at all).
Alternative medicine offers numerous options for treating depression, but only one has strong scientific evidence behind it: the herb St. Johns wort. The evidence for this herbs effectiveness is nearly as comprehensive as what is required of a drug prior to approval. However, this herb also presents numerous safety risks, including interactions with many drugs. (See the full St. John’s wort article for more information.)
St. Johns Wort
St. Johns wort (Hypericum perforatum)is a common perennial herb, with many branches and bright yellow flowers, that grows wild in much of the world. Its name derives from the herbs tendency to flower around the feast of St. John (wort simply means "plant" in Old English). The species name perforatum derives from the watermarking of translucent dots that can be seen when a leaf of the plant is held up to the sun.
St. Johns wort has a long history of use in emotional disorders. It began to be considered as a treatment for depression early in the twentieth century, and when pharmaceutical antidepressants were invented, German researchers looked for similar properties in St. Johns wort.
Today, St. Johns wort is one of the best-documented herbal treatments, with a scientific record approaching that of many prescription drugs. Indeed, this herb is a prescription antidepressant in Germany. It is covered by that countrys national health-care system and is prescribed more frequently than any synthetic drug.
Research suggests that St. Johns wort is effective in about 55% of cases. As with other antidepressants, the full benefit takes about 4 to 6 weeks to develop. The most common reported effects are brightened mood, increased energy, and improved sleep.
St. Johns wort should never be relied on to treat very severe depression. If you or a loved one is feeling suicidal, unable to cope with daily life, paralyzed by anxiety, incapable of getting out of bed, unable to sleep, or uninterested in eating, see a physician at once. Drug therapy may save your life.
St. Johns wort appears to be reasonably safe when taken alone. However, there is good reason to believe that it may interfere with the effectiveness of numerous medications, including contraceptives, transplant rejection drugs, and treatments for HIV infection.
What Is the Scientific Evidence for St. Johns Wort?
Numerous double-blind placebo-controlled studies enrolling a total of more than 1,000 people have compared St. Johns wort to placebo.
Taken together, the results strongly suggest that St. Johns wort is an effective treatment for mild to moderate depression. Several studies have found that St. Johns wort is equally as effective as standard antidepressants, but causes fewer side effects. For example, four double-blind trials enrolling a total of more than 600 individuals have compared St. John’s wort to either fluoxetine (Prozac) or sertraline (Zoloft). In all these studies, the herb proved at least as effective as the drug, and caused fewer side effects.
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. However, two studies cannot overturn a body of positive research. Approximately 35% 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 sertraline (Zoloft) also failed to prove effective. The reason for these negative outcomes is not that Zoloft (or Prozac, or any other drug) does not work. Rather, statistical effects can easily hide the benefits of a drug, especially in a condition like depression where there is as a high placebo effect and no really precise method or measuring symptoms.
Thus, unless a whole series of studies find St. John’s wort ineffective, especially trials in which a comparison drug treatment does prove effective, St. John’s wort should still be regarded as probably effective for major depression of mild to moderate severity.
For more information, including dosage and safety issues, see the full St. Johns wort article.
Other Proposed Treatments for Depression:
There are a number of other herbs and supplements that may be helpful in depression, although the evidence for them is nowhere near as strong as that for St. Johns wort.
Phenylalanine
Phenylalanine is a naturally occurring amino acid that we all consume in our daily diets. There is some evidence that phenylalanine supplements may help reduce symptoms of depression.
What Is the Scientific Evidence for Phenylalanine?
Phenylalanine occurs in a right-hand and a left-hand form, known as D- 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 against the antidepressant drug imipramine (taken in daily doses of 100 mg) and found them to be equally effective. A total of 60 individuals were randomly assigned to either one group or the other and followed for 30 days. D-phenylalanine worked more rapidly, producing significant improvement in only 15 days.
Another double-blind study followed 27 people, 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 30 days, the two groups had improved by the same amount.
Unfortunately, there do not seem to have been any properly designed studies that compared phenylalanine to placebo. Until these are performed, phenylalanine cannot be considered a proven treatment for depression, but it is certainly promising.
For more information, including dosage and safety issues, see the full phenylalanine article.
5-HTP
A new, up-and-coming treatment for depression is 5-HTP (5-hydroxytryptophan). When the body sets about manufacturing serotonin, it first makes 5-HTP. The theory behind taking 5-HTP as a supplement is that providing the one-step-removed raw ingredient might raise serotonin levels. However, this plausible idea has not been proven.
The amino acid tryptophan used to be recommended as a treatment for depression on the same basis. It is one step back in the chain, being turned by the body into 5-HTP and then to serotonin. However, tryptophan was removed from the market several years ago when a contaminant caused a terrible and often permanent illness in many people who took the supplement. Because 5-HTP is made by a completely different manufacturing process (starting from a plant rather than bacteria), one would not expect the same contaminant to be present. Disturbingly, however, recent reports suggest otherwise.
Like St. Johns wort, 5-HTP is used mainly in Europe, where many physicians find it an effective treatment for both depression and insomnia.
What Is the Scientific Evidence for 5-HTP?
There have been several preliminary studies of 5-HTP. The best of these trials was a 6-week study of 63 people given either 5-HTP (100 mg 3 times daily) or an antidepressant in the Prozac family (fluvoxamine, 50 mg 3 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 fluvoxamine. The only real complaint was occasional mild digestive distress.
For more information, including dosage and safety issues, see the full 5-HTP article.
Ginkgo: Improves Mental Function, but May Help Depression, Too
Ginkgo is used mainly for age-related mental decline such as that from Alzheimers 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 study, published in 1990, evaluated this effect in 60 people who suffered from depressive symptoms along with other signs of dementia. The results showed significant improvements among participants given ginkgo extract instead of placebo.
Another study followed 40 depressed individuals over the age of 50 who had not responded successfully to antidepressant treatment. Those who were given ginkgo showed an average drop of 50% in scores on the Hamilton Depression scale, whereas the placebo group showed only a 10% improvement.
In 1994 an interesting piece of research was reported that may shed light on the mechanism by which ginkgo could 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. Instead of raising the level of serotonin, like Prozac does, ginkgo may thus improve the brains ability to respond to serotonin (at least in older people). However, this is still highly speculative. More experimentation is needed to clarify the mechanism of ginkgos action and to better quantify its effectiveness in depression.
For more information, including dosage and safety issues, see the full ginkgo article.
Phosphatidylserine: Good for Mental Function, May Also Help Depression
Phosphatidylserine is another treatment used mainly for mental decline in the elderly that may also offer antidepressant benefits.
For more information, including dosage and safety issues, see the full phosphatidylserine article.
SAMe
Another European supplement treatment for depression now arrived in the United States is SAMe (S-adenosylmethionine). SAMe is a very important biological molecule that occurs throughout the body. Its job is to hand over a chemical fragment called a methyl group to other chemicals that need it.
The evidence for SAMe as an antidepressant is provocative but far from definitive.
Several double-blind placebo-controlled studies have found SAMe effective in relieving depression, but they were all small and poorly reported, and many used an injected form of the supplement. Furthermore, the most recent trial, a double-blind placebo-controlled study of 133 depressed patients, failed to find intravenous SAMe more effective than placebo. Researchers resorted to questionable statistical manipulation of the data to show benefit.
A recent 6-week double-blind trial of 281 individuals with mild depression compared oral SAMe to imipramine. The results showed that the two treatments were about equally effective.
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.
For more information, including dosage and safety issues, see the full SAMe article.
Folate
In the body, the vitamin folate works in tandem with SAMe. Studies have suggested that depressed individuals have reduced folate levels, and that folate supplements may help alleviate depression. In addition, patients with particularly low folate levels have been found to respond poorly to antidepressants.
Based on these findings, a study examined the effects of combining folate with antidepressant treatment.
This 10-week double-blind placebo-controlled trial of 127 individuals with severe major depression found that folate supplements at a dose of 500 mcg daily significantly improved the effectiveness of fluoxetine (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.
For more information, including dosage and safety issues, see the full folate article.
Exercise
Exercise may be helpful for depression. In a review published in the journal Sports Medicine, authors Tim Meyer and Andreas Broocks analyzed the published research on this subject. Their conclusion: a very qualified "yes."
In seven out of eight studies reviewed, various forms of exercise proved beneficial for depression. Aerobic exercise, weight training, dancing, and racketball all produced improvements in mood as compared to no exercise.
However, the findings of the one negative study reported in this review cast doubt on the others. In this trial, some participants exercised, while others took a course at school and didnt exercise at all. The results: equal benefits 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. Youd 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 signficantly their depression improved.
Other Treatments
A 4-week, double-blind, placebo-controlled trial evaluated the potential benefits of fish oil in 20 indviduals with depression. All but one participant were also taking standard antidepressants and had been taking them for at least 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. Six of 10 participants given fish oil, but only one of 10 given placebo, showed at least a 50% reduction in depression scores by the end of the trial. (A reduction of this magnitude is considered a “cure.”)
A preliminary controlled trial found evidence that acupuncture might be helpful for the treatment of mild depression.
A growing body of small studies suggests that a special form of electromagnetic therapy called transcranial magnetic stimulation (TMS), may be helpful for depression.
Weak evidence suggests that the nutritional substance inositol might be helpful in depression when taken in extremely high doses (12 g daily). However, a double-blind study of 42 people with severe depression that was not responding to standard antidepressant treatment found no improvement when inositol was added. Keep in mind that although this is a nutritional substance, when taken in such enormous doses, its safety cannot be assured.
Preliminary evidence suggests that the substance acetyl-L-carnitine may be useful for depression in the elderly.
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 B6 are common and B12 deficiencies occur more often with advancing age, so it may be a good idea to take these vitamins on general principles.
Intriguing, but highly preliminary, evidence suggests that deficiencies in essential fatty acids may increase the risk of depression; it is possible that fish oil supplements could therefore help prevent depression.
The herbs and supplements beta-carotene, damiana, NADH, pregnenolone, and tyrosine are also sometimes recommended for depression, but there is little evidence as yet that they really work.
Not Recommended Treatments:
The herb yohimbe and the hormone DHEA are sometimes suggested for depression, but because of potential risks we do not suggest using them except under the supervision of a qualified health-care professional (if at all).