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Depression

Introduction

What should I know about depression?

Depression has been part of the human condition since antiquity. Hippocrates, the ancient Greek "Father of Medicine," is generally credited with the first description of an emotional disorder and is thought to have coined the term "melancholia," literally translated as "black bile." (1)

Although life is filled with unexpected events such as the death of a loved one, loss of a job, major illness, or other catastrophic events, not everybody becomes depressed. Most individuals suffer only temporary feelings of depression and find ways to adjust to life’s challenges. However, there are certain individuals who experience a major depressive episode when faced by stressful situations.

Depression has been classified as a mood disorder or "affective" disorder. Mood is defined as a powerful, sustained emotion that, in the extreme, markedly affects a person’s perception of the world and ability to adequately function in society. (2) Mood disorders are among the most common health problems doctors see every day. Mood disorders are divided into two major categories: depressive disorders and bipolar disorders.

Depression affects approximately 5 percent of the population at any given time, and about 30 percent of adults will suffer from depression over a lifetime. (3) Commonly thought of as a disorder of young to middle adulthood, with an average age of onset in the late 20's, depression is also a common psychiatric illness in the elderly. (4) Women are two to three times more likely to experience depression than men. (5)

Mood disorders, depression, and anxiety are common illnesses in our society. Lost work time, family conflicts, personal strife, and other consequences of the disease can eventually lead to complete disruption of one’s life. Depression and mood disorders have become increasingly recognized as widespread health problems. In spite of this they are often under-diagnosed and under-treated. (6)

The causes of depression are too complex to be totally explained by a single social, biological, or developmental theory. Several factors seem to work together to trigger depressive disorders. Heredity does seem to have a role, as studies have shown. Depressive disorders and suicide tend to run in families, and first-degree relatives of patients with depression are one and one half to three times more likely to develop depression than people with no depression in the immediate family. (7)

Depression is not simply "all in the head." Depression has physical causes, linked to abnormalities in brain chemistry. The symptoms of major depression consistently reflect changes in "neurotransmitters," substances that regulate function of the brain and nervous system. The neurotransmitters closely related to depression are norepinephrine, serotonin, and dopamine. (8)

Serotonin is a key neurotransmitter for maintaining mental and emotional health. Low serotonin plays a big role in depression. Prolonged stress—physical, mental, or emotional can deplete the body’s serotonin supply. A host of other health problems can contribute to depression by robbing serotonin, including adrenal exhaustion, hypothyroidism, heavy metal toxicity, and "leaky gut" syndrome with subsequent food intolerance. Deficiencies in nutrients such as vitamin B12, folic acid, and certain amino acids can also be involved.

Statistic

World Health Organization, 2002.

  • Currently 121 million people suffer from depression and the burden of depressive illness is rising.
  • The world over, twice as many women suffer from depression as men.

Mental Health foundation of New Zealand, 2007.

  • One person in every eight (12.6% of the population) will have a Major Depressive Episode in their lifetime.
  • One in five females (19.4% of the female population) and one in ten males (10% of the male population) are likely to experience a depressive disorder.

National Institute of Mental Health, 1999.

    19 million people in the US suffer from depression at one time each year. 1 in 10 adults suffer from depression each year. 2 million of the 34 million Americans age 65 and older suffer from depression. Treatments alleviate 80% of the symptoms of depression. Women experience depression roughly at twice the rate as men. This ratio exists regardless of racial and ethnic background or economic status.

Signs and Symptoms

The following list does not insure the presence of this health condition. Please see the text and your healthcare professional for more information.

The American Psychiatric Association has a list of criteria that are used to diagnose depressive disorders. These criteria include:

  1. Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from the individual’s previous emotional state; at least one of the symptoms is either depressed mood or loss of interest or pleasure.
    • Depressed mood most of the day, nearly every day.
    • Markedly diminished interest in pleasure in all, or almost all, activities.
    • Significant weight loss (not dieting) or weight gain, or increase or decrease in appetite nearly every day.
    • Insomnia or excessive sleep nearly every day.
    • Sluggishness or agitation nearly every day.
    • Fatigue or loss of energy nearly every day.
    • Feelings of worthlessness or excessive or inappropriate guilt (may be delusional) nearly every day.
    • Diminished ability to think or concentrate, or indecisiveness.
    • Recurrent thoughts of death, recurrent suicidal thoughts without a specific plan, or a suicide attempt or specific suicide plan.
  2. The symptoms cause significant distress or impair the person’s ability to function in everyday tasks. The symptoms are not due to the direct psychologic effects of a substance or general medical condition.
The symptoms occur most of the day, nearly every day and can not be due to any drugs, substance or general medical condition  

Treatment Options

Conventional

Depression is a one-two punch that knocks the sufferer out of the ring on a daily basis. Number one, the symptoms themselves make life miserable. Number two, the depressed individual struggles to function and keep up with the life’s normal demands. Conventional treatment for depression is aimed both at reducing symptoms and helping the individual regain the ability to function they once enjoyed. Usually the treatment includes psychotherapy and the use of anti-depressant medications.

The most commonly used drugs for uncomplicated depression are the tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors, (SSRIs). If a patient does not respond to one type, therapy is often switched to the other. Of the tricyclic antidepressants, amitriptyline and imipramine are the most extensively studied and used. TCAs work by blocking the "reuptake" of norepinephrine and serotonin into brain and nerve cells. These neurotransmitters conduct electrical impulses from cell to cell, allowing us to think and feel. Once a neurotransmitter molecule has carried an impulse across the gap between two neighboring cells, called the "synapse," the molecule is reabsorbed. If neurotransmitters are in short supply to begin with, brain and nerve function may be impaired. By inhibiting neurotransmitter reuptake, TCAs in effect increase the amount available in the synapse.

TCAs, unfortunately are like a shotgun; they interfere with other neurotransmitters that regulate a variety of body functions. For this reason, TCAs have a lot of side effects. SSRIs, on the other hand, are much more precise. These drugs block the re-uptake of serotonin by itself, without touching other neurotransmitters. SSRI’s have fewer side effects and are generally preferred by physicians over the traditional TCAs. People who fail to benefit from a SSRI may respond to a TCA, and vice versa.

If neither type of medication works, others are considered. Buproprion blocks the reuptake of dopamine, another important neurotransmitter in the brain. Mirtazapine a tetracyclic antidepressant with mixed effects on both serotonin and norepinephrine, may be prescribed. Triazolopyridine (trazodone or nefazodone), has a dual action as a serotonin antagonist and also a reuptake inhibitor.

Yet another type of anti-depressants are the "monoamine oxidase inhibitors" such as phenelzine, and tranylcypromine. Commonly known as "MAO inhibitors," these drugs are used in cases of atypical depression. Symptoms of atypical depression that are usually improved by MAO inhibitors include mood reactivity, irritability, excessive sleeping, overeating, bodily agitation, and over sensitivity to rejection. (9)

Nutritional Suplementation


S-Adenosylmethionine (SAMe)

S-adenosyl methionine (SAMe), widely available as a dietary supplement, is one of the most studied non-drug antidepressants. SAMe is a naturally occurring substance manufactured in the body from the amino acid methionine. It is critical for production of neurotransmitters.

Italian researchers tested SAMe in the 1970s as a treatment for schizophrenia. SAMe was found to have antidepressant effects, and clinical studies soon followed that validated these findings. A recent meta-analysis (a research method that pools the data from many small studies to draw a conclusion based on large numbers of subjects) concluded, "The efficacy of SAMe in treating depressive syndromes and disorders is superior with that of placebo and comparable to that of standard tricyclic antidepressants. Since SAMe is a naturally occurring compound with relatively few side effects, it is a potentially important treatment for depression." (10) Several studies report that SAMe is more effective than tricyclics. (11) , (12)

In another meta-analysis, the benefits of SAMe as an antidepressant were again confirmed. SAMe was found to provide better antidepressant benefits than a placebo ("dummy pill") and it worked as well as the standard tricyclic antidepressant medications, with relatively few side effects. The results of this meta-analysis prompted the authors to state that SAMe is, "a potentially important treatment for depression." (13)

Clinical trials show SAMe is fast acting, adding to its value as a natural antidepressant. (14)


5-Hydroxytryptophan (5-HTP)

Tryptophan and 5-hydroxytryptophan (5-HTP) are the starting material for production of serotonin in the body. Tryptophan is an essential amino acid that the body cannot manufacture on its own. Tryptophan can be obtained only in food or supplements. The body converts tryptophan into 5-HTP, which in turn is converted into serotonin. (15) There is ample evidence that tryptophan depletion causes reduced synthesis of serotonin, which results in depression and other mood disorders. (16)

In 1989, the FDA removed tryptophan from the market due to some contaminated batches that caused a number of deaths. It is now available by prescription through compounding pharmacies, and it is also used in intravenous feeding and in infant formulas. However, tryptophan is still not available to the general public as a nutritional supplement. Since tryptophan was removed from the market, 5-HTP has gained recognition as an effective substitute in natural therapy for anxiety, depression, and sleep disorders. Either substance can be used to enhance serotonin synthesis in the brain. (17) It is now recognized that 5-HTP is more effective at elevating serotonin levels than tryptophan.

People taking anti-anxiety drugs or other antidepressants should not take tryptophan or 5-HTP without the close supervision of a qualified health care professional because it can increase both the effect and the toxicity of antidepressant drugs.


Phenylalanine, Tyrosine

Phenylalanine and tyrosine are additional amino acids the body needs to produce neurotransmitters. These nutrients are used to manufacture dopamine, norepinephrine, and epinephrine, three neurotransmitters that influence and regulate mental and emotional states.

Antidepressant activity has been reported in studies using D-phenylalanine or with a mixture of D-phenylalanine and its twin amino acid, L-phenylalanine (DLPA). Several studies have reported results equal to or better than tricyclic antidepressants, without side effects. (18) , (19) People usually respond within two to four weeks, and in one study, severely depressed patients responded well. (20)

Individuals with high blood pressure should only take phenylalanine under close supervision of their primary care provider. It should not be used by people with phenylketonuria (PKU), melanoma, and those taking MAO inhibiting antidepressants.

Tyrosine is synthesized from phenylalanine and thus, it is not an essential amino acid. However, like phenylalanine, tyrosine is also intimately involved in the production of dopamine, epinephrine, and norepinephrine. Therefore, the benefits and effects of tyrosine are similar to those reported for phenylalanine. Although several small trials with depressed patients have reported impressive results, (21) , (22) no large well-controlled studies on tyrosine and depression have been conducted to date.


Dehydroepiandrosterone (DHEA)

Dehydroepiandrosterone (DHEA) is a hormone that can be safely taken in supplement form. DHEA’s effectiveness as a treatment for depression has not yet been tested in large-scale clinical trials, but initial results from a few small studies look promising.

Therapy with DHEA is not recommended for individuals with a history of prostate or breast cancer. It is prudent to take DHEA under the supervision of a health professional, and users should have their DHEA levels measured in order to determine the appropriate individual dose.


Omega-3 Fatty Acids

Studies show a relationship between symptoms of depression and the a ratio of low omega-3 to high omega-6 fats in the diet. (23) , (24) The quantity and ratio of omega-3 to omega-6 is critical because these fatty acids serve as building blocks for prostaglandins, a group of hormone-like substances that regulate many important aspects of biological function throughout the body. A clinical trial evaluated the antidepressant effects of an Omega-3 oil in 70 patients using an adequate dose of a standard antidepressant yet who continued to experience depression. Using three different scales to rate depression, the group taking 1gram/day (g/d) of ethyl-eicosapentaenoate had significantly better outcomes than placebo on all three rating scales. The 2g/d and 4g/d, did not do as well as the 1g/d group. (25) In a book titled Omega-3 Oils, Donald O. Rudin, M.D. reports that giving patients omega-3 supplements often improves mood and relieves depression within one to two weeks. (26)


Vitamin B6

Vitamin B6 is required for the conversion of tryptophan to serotonin discussed earlier. Vitamin B6 deficiency may result in symptoms of anxiety and depression, due to decreased serotonin production. (27) Numerous drugs can deplete vitamin B6, which can often lead to depression.

Oral contraceptives are known to deplete vitamin B6, potentially triggering depression in susceptible women. In one particular study, administration of 40mg of vitamin B6 daily restored normal biochemical values and also relieved the clinical symptoms in the vitamin B6 deficient women taking oral contraceptive. (28) Other important categories of drugs that can deplete vitamin B6 include corticosteroids, theophylline-containing medications, hydralazine-containing vasodilators,loop diuretics, and estrogen replacement therapy medications. (29)


Vitamin B12

Vitamin B12 deficiency can result in depression. B12 deficiency occurs much more frequently in the elderly. (30) , (31) A Norwegian mental hospital measured the B12 level of every patient over 30 years old who was admitted during a one-year period. The results showed that the percentage of mental patients with below normal vitamin B12 levels was 30 times higher than in the normal population in that area. (32)

Commonly prescribed drugs that can deplete vitamin B12 include aminoglycosides, phenytoin, biguanides, corticosteroids, zidovudine, and other related antiviral drugs, the "fibrate" cholesterol-lowering drugs, bile acid sequestrants, timed release potassium chloride tablets, oral contraceptives, colchicine, H-2 receptor antagonists, and proton pump inhibitors. (33)


Folic Acid

According to doctors from the Department of Psychiatry at Harvard Medical School, depressive symptoms are the most common neuropsychiatric signs of folic acid deficiency. (34) In one study, patients with major depression with low folic acid levels were treated with methylfolate (15 mg/day) or a placebo. At both three and six months, patients showed substantial improvements in depression scores compared to the placebo controls. Overall, folic acid supplementation significantly enhanced recovery from psychiatric illness. (35)

The following classes of drugs are capable of depleting of folic acid: antacids, anticonvulsants, biguanides, corticosteroids, aspirin and salicylates, nonsteroidal anti-inflammatory agents, bile acid sequestrants, oral contraceptives, and the H-2 receptor antagonists. (36)

Herbal Suplementation


St. John's Wort

St. John’s is one of the world’s most popular herbal treatment for depression, thanks to its extensive use in Europe. The scientific evidence for St. John’s wort, gathered in a number of fairly large clinical trials, is solid. European physicians write millions of prescriptions for St. John’s wort annually and it is one of the most publicized herbs in the U.S.

So far, the studies have shown St. John’s wort to work effectively in mild to moderate depression; whether it works as well in severe depression has not been tested yet. (37) , (38) , (39)

Studies with St. John’s wort have used an extract of the herb standardized to contain 0.3% hypericin, which is one of the herb’s main ingredients. The established effective dose is 300 mg of this St. John’s wort extract, taken three times a day. It is viewed as safe and effective in by the German Commission E, which is a recognized authority on herbal medicine.

One possible drawback in the use of St. John’s wort has surfaced. St. John’s wort seems to stimulate liver enzymes which eliminate drugs from the body. This means that taking the herb along with certain drugs might prevent the drugs from working as they should. Interactions along this line between St. John’s wort and anticoagulants, indinavir, cyclosporin, digoxin, ethinyl estradiol/desogestrel, and theophylline have occurred. (40) Also, several reports have suggested that taking of St. John’s wort and SSRIs together could raise serotonin levels too much. "Serotonin syndrome" could result with symptoms that include sweating, tremor, confusion, flushing, and agitation. (41) , (42) Use St. John’s wort with caution if individuals are on these medications.


Ginkgo

Ginkgo is among the oldest living species on earth and has been used extensively as a medicinal herb worldwide for centuries. It is the most frequently prescribed herb in Europe.

Overall, Gingko is considered a tonic for the circulatory system. It may increase blood flow in the brain, improve delivery of oxygen and nutrients to brain tissues, and help eliminate cellular waste. (43)

Ginkgo has also been used to treat impotence, especially when associated with antidepressant therapy. (44) , (45) Ginkgo has traditionally been used as a supportive herb treating difficult cases of depression, often in combination with St. John’s wort. (46)


Rhodiola

Rhodiola has long been used in traditional folk medicine in China, Serbia, and the Carpathian Mountains of the Ukraine. In the former Soviet Union, it has long been used as an "adaptogen," an herb that decreases fatigue and increasing the body’s natural resistance to stress. Rhodiola seems to enhance the body's physical and mental work capacity and productivity, working to strengthen the nervous system, fight depression, enhance immunity, elevate the capacity for exercise, enhance memorization, improve energy levels, and possibly prolong the life span. (47)

For the treatment of depression, active ingredients of rhodiola, namely rosavin and salidroside, in animal studies seem to enhance the transport of tryptophan, and 5-HTP, the serotonin "precursors" discussed earlier into the brain. and decrease the action of COMT (catechol-O-methyltransferase), an enzyme that breaks down serotonin. (48) Russian scientists have used Rhodiola alone or in combination with antidepressants to enhance mental state and decrease the symptoms of SAD or Seasonal Affective Disorder common to Northern European countries. Additional studies need to be performed to verify its effectiveness for this particular function.

Diet & Lifestyle

    Eliminate sugar, caffeine, and alcohol. Identify and eliminate food allergies. Exercise. Light therapy. Stress reduction can take form in a variety of ways. Some of the more structured forms include; counseling, tai chi, yoga, meditation, deep breathing.

References

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