Depression Protocol

No research exists on the use of in children. More importantly, any child suspected of being depressed deserves a psychiatric evaluation.

As with all antidepressants, it takes a while for the effects of hypericum to be felt. Many patients will notice a change in 2-3 weeks, although it may take as long as 4 to 6 weeks. Hypericum's side effects are very mild and are typically limited to slight gastrointestinal irritation.

Caution: Certain light-skinned sheep in Australia have become more sensitive to the sun and may experience serious sunburns after grazing on large amounts of the hypericum leaf. While sunburn does not appear to be a common problem among people taking the recommended doses of hypericum for depression, many practitioners recommend their patients with sun-sensitive skin be sure to wear sunscreen or cover up. The same caution applies to people taking medications such as tetracycline that increase sun sensitivity.

Because of potential adverse herb-drug interactions, is not recommended in combination with monoamine oxidase (MAO) inhibitors such as Parnate and Nardil or with the SSRIs (serotonin reuptake inhibitors), Prozac, Luvox, Paxil, Zoloft, and Celexa. This is because may further augment the same neurotransmitters that the drugs increase, leading to dangerously high levels. If you wish to switch from an antidepressant drug to , talk to your physician about safe ways to do this.

has been shown to diminish the effectiveness of a growing list of drugs: digoxin, warfarin, phenprocoumon, cyclosporin, amitryptiline, theophylline, oral contraceptives, indinavir, and some anticancer drugs. Primarily, it lowers the blood levels of these drugs. How? Research suggests that active ingredients in the herb crank up the production of a liver enzyme called CYP3A, which breaks down a host of compounds, including many drugs. In other words, accelerates the liver's breakdown of these drugs (Markowitz et al. 2000; Moore et al. 2000; Vogel 2001).

Because of the growing list of herb-drug interactions, two regulatory groups, the American Herbal Products Association (AHPA) and the Consumer Healthcare Products Association (CHPA), have made labeling recommendations that alert consumers not to combine with prescription medication without first asking a health professional (HerbalGram 2000).

has been reported to aggravate mania, so it should be used with caution by individuals with bipolar disease. As with all antidepressants, does not work for everyone with depression.

Critics of this herbal supplement point to a study where was no more effective than placebo in alleviating depression. The fact that it has the potential to adversely interact with a wide variety of prescription drugs limits its use to people who are not taking other prescription medications.

One advantage of is that it is very inexpensive. It costs far less than prescription drugs or SAMe. The most compelling reason to choose SAMe over , however, may be the fact that over the past 5 years, Life Extension members who have been offered the choice of either SAMe or have chosen SAMe by a factor of over ninety to one. This real world finding indicates that people are finding a greater effect with SAMe than .

5-Hydroxytryptophan (5-HTP)
To make serotonin, the body first converts the amino acid L-tryptophan to 5-hydroxytryptophan (5-HTP). In people with a personal or family history of depression, a diet devoid of tryptophan can cause moods to crash in a matter of hours (Moreno et al. 2000). Some, but not all studies have shown that supplemental L-tryptophan relieves depression (Moller et al. 1980) and mania (Chouinard et al. 1985). Unfortunately, contaminated tryptophan was linked with a serious disorder called eosinophilia-myalgia syndrome (EMS), causing this supplement to be removed from the U.S. market in 1989.

Does eating more protein help? Although tryptophan is a component of most protein-rich foods, raising brain levels of this amino acid through diet is tricky. In order to cross from the blood into the brain, tryptophan must first bind to a transport molecule, which it shares with five other amino acids. The L-tryptophan concentration in foods is low relative to other amino acids. According to Timothy C. Birdsall, N.D., Director of Naturopathic Medicine, at the Midwestern Regional Medical Center in Zion, Illinois, "as little as one percent of dietary L-tryptophan may be transported into the central nervous system."

Although several reports in the published literature show that 5-HTP may be as effective as some antidepressants, the Life Extension Foundation does not endorse its use in the U.S based on certain findings.

The process by which 5-HTP is converted into serotonin is called decarboxylation. If decarboxylation occurs before 5-HTP is absorbed by the brain, blood levels of serotonin will elevate significantly, but very little serotonin will enter the brain.

When Europeans take 5-HTP, they are often prescribed the decarboxylase inhibitor carbidopa that prevents 5-HTP from being converted into serotonin until it reaches the brain. Americans do not take carbidopa with 5-HTP and the result is possible serotonin overload in the blood, with virtually no serotonin reaching the brain.

Americans taking 5-HTP are more vulnerable to blood serotonin overload because, unlike most Europeans who are vitamin deficient, Americans who use 5-HTP usually take vitamin B6 as well. Vitamin B6 rapidly converts 5-HTP into serotonin before it reaches the brain. Even when combined with carbidopa, high levels of vitamin B6 will break through the carbidopa barrier and ensure that 5-HTP converts into serotonin in the blood before it can reach the brain. Excess serum serotonin is especially dangerous in those with underlying coronary artery disease as serotonin in the blood can induce arterial constriction.

Omega-3 Fatty Acids
According to Michael A. Schmidt, Ph.D., author of Smart Fats (1997), our culture consumes too much saturated fat (found in animal fats) and omega-6 fatty acids (found in the corn and soybean oils used in so many processed foods), and too little of the omega-3 fatty acids (found in fish oils and some plants such as flax seed). This sort of imbalance has been associated with increased levels of depression (Hibbeln et al. 1995).

Omega-3 fatty acids control various enzyme systems, cell membrane fluidity, inflammatory processes, and several aspects of neurotransmitter function. Depressed people seem to have low levels of omega-3 fatty acids in their diet and in their cell membranes (Edwards et al. 1998). One study in the Archives of General Psychiatry found that 9.6 grams a day of omega-3 fatty acids for 4 months benefited people with bipolar disorder (alternating episodes of depression and mania) significantly more than a placebo (olive oil) (Stoll et al. 1999).

Michael A. Schmidt recommends eating cold-water fish 2-3 times a week. Fish contains docosapentaenoic acid (DHA), which is particularly critical to brain function. Eggs, depending upon what the chickens eat, contain varying amounts of DHA. Although the conversion is not terribly efficient, the body can also create eicosapentaenoic acid (EPA) and DHA from the alpha-linolenic acid (ALA) found in green leafy vegetables, flaxseed, chia seeds, rapeseed, pumpkin seeds, Brazil nuts, and walnuts.

When using supplements, Schmidt recommends a daily dose of between 400-1000 mg of DHA and 400-1000 mg of EPA.

Caution: Because of fish oil's mild blood-thinning effect, high-dose omega-3 supplements should only be combined with anticoagulant drugs under the supervision of a physician. Fish, however, is fine to eat.

Ginkgo (Ginkgo biloba)
An extract from the leaf of the ginkgo tree increases blood circulation to the head and other parts of the body. It also acts as an antioxidant and stabilizes cell membranes and scavenges free radicals, particularly in the brain. Although better known for improving mental function in normal people and those with Alzheimer's and other types of depression, ginkgo may be of value in older people with depression. In one study, elderly depressed people with mild depression who had failed to improve on antidepressant drugs did respond when a Ginkgo biloba extract was added (Schubert et al. 1993). Because ginkgo improves circulation, it has been proposed for reversing the sexual dysfunction associated with some antidepressant drugs.

A study conducted in 1999 failed to find that a ginkgo extract alleviated the depression of seasonal affective disorder (Lingaerde et al. 1999).

In rats, Ginkgo biloba extract increases the number of serotonin binding sites in old, but not young rats. This suggests the herb might counteract some of the reduction of serotonin binding sites associated with human aging (Huguet et al. 1994). The recommended dosage is 120 mg a day of a Ginkgo biloba extract standardized to 24-28% ginkgo flavonglycosides.

Caution: Because ginkgo has a mild blood-thinning effect, it could theoretically cause bleeding problems if combined with blood-thinning drugs such as warfarin, heparin, aspirin, or pentoxifylline.

Ginseng
There are two main types of ginseng; the stronger Asian variety (Panax ginseng) and the milder American ginseng (Panax quinquefolius). Eleuthero or Siberian ginseng (Eleutherococcus senticosus), is a relative of ginseng that, though mild, has similar properties. All three plants are adaptogens, substances that help the body adapt to stress. Eleuthero ginseng, however, has not demonstrated antidepressant activity, according to the medical literature.

In the Orient, ginseng has long been prized as an overall tonic and rejuvenator. Practitioners of Traditional Chinese Medicine generally do not recommend daily use of Asian ginseng in people under 40, unless they are in a stressful occupation or environment or are debilitated. Indeed, the only research examining the potential benefit of ginseng in depression has focused on older women. Specifically, two studies have found that Asian ginseng (Panax ginseng) reduces depression and generally improves well-being in menopausal women (Tode et al. 1999; Wiklund et al. 1999).

Caution: Panax ginseng, but not eleuthero, has mild estrogenic effects. Rarely, it may cause menstrual abnormalities and breast tenderness in women. Asian ginseng can be stimulating. At high doses, side effects such as elevated blood pressure, increased heart rate, and insomnia have been reported. Such stimulation may be augmented when ginseng is combined with caffeine. Avoid Asian ginseng if you are pregnant or have heart irregularities, high blood pressure, or a family history of high blood pressure. (American ginseng and Siberian ginseng don't carry these cautions.) If you have diabetes, do not take Asian or American ginseng on a regular basis unless you are under the care of a physician. Because true ginseng can lower blood sugar levels, insulin dosages need to be adjusted. This herb may also interact with MAO inhibitors and blood-thinners such as warfarin.

Adrafinil
This is a European antidepressant drug that is being successfully used by Europeans and Americans who import it for personal use. The dose is usually 2 tablets twice a day.

DL-Phenylalanine and L-Tyrosine

DL-Phenylalanine and L-Tyrosine are both amino acids. Our bodies can convert DL-phenylalanine to L-Tyrosine and DL-phenylethylamine (PEA). L-Tyrosine is the precursor to several neurotransmitters, including norepinephrine and dopamine. PEA is found in high concentrations in chocolate, occurs naturally in the brain, and seems to elevate mood. Low urinary levels have been found in depressed patients. Both amino acids have been shown to increase urinary and brain levels of PEA.

Most neurobiologists believe that insufficient activity of serotonin and norepinephrine is central to the onset of depression. In the 1970s and 1980s, many people were treated with neurotransmitter precursors to alleviate depression. Meyers (2000) did a literature search of the early studies (1970s and1980s) on neurotransmitter precursor loading, focusing mainly on 5-HTP and tryptophan, the serotonin precursors, and phenylalanine and L-Tyrosine, the dopamine and norepinephrine precursors. He concluded that although it was difficult to draw definitive conclusions from the literature, precursor loading may be of therapeutic value for patients with mild to moderate depression (Meyers 2000).

Insufficient activity of the neurotransmitters serotonin and norepinephrine is a central element of the model of depression most widely held by neurobiologists today. In the late 1970s and 1980s, numerous studies were performed in which depressed patients were treated with the serotonin precursors L-tryptophan and 5-hydroxytryptophan (5-HTP), and the dopamine and norepinephrine precursors L-Tyrosine and L-phenylalanine. The nature of the studies makes it difficult to draw firm conclusions regarding the efficacy of neurotransmitter precursors for treating depression. While there is evidence that precursor loading may be of therapeutic value, particularly for the serotonin precursors 5-HTP and tryptophan, more studies of suitable design and size might lead to more conclusive results. However, the evidence suggests neurotransmitter precursors can be helpful in patients with mild or moderate depression.

Deprenyl (selegiline) is a drug approved for use in Parkinson's disease that irreversibly inhibits monoamine oxidase type B (MAO-B). Monoamine oxidase is an enzyme that inactivates the monoamine neurotransmitters norepinephrine, serotonin and dopamine.

The action of Deprenyl and L-phenylalanine was studied in 155 unipolar depressed people. Both oral and intravenous administration of the combination showed beneficial effects in 90% of outpatients and 80.5% of inpatients. The researchers concluded that the antidepressive action was based on the accumulation of L-phenylalanine in the brain (Birkmayer et al. 1984).

Phenylalanine comes in two chemical forms: L-phenyalanine and its mirror image D-phenylaline. When using a 50/50 mix of both forms, called DL-phenylalanine, the typical dosage is 500-1000 mg a day. For L-Tyrosine, the typical recommended dosage is between 500-1500 mg a day.

Caution: Although L-Tyrosine appears to be generally safe, high dosages have been reported to cause nausea, diarrhea, vomiting, or nervousness.

For phenylalanine, dosages over 1500 mg a day can cause anxiety, headache, and mildly elevated blood pressure. People with phenylketonuria (a rare, congenital disease wherein this amino acid cannot be metabolized) should not take it. This amino acid may also increase the side effects of antipsychotic medications.

Safety and appropriate dosing of supplementary phenylalanine and L-Tyrosine has not been established for children, pregnant or nursing women, or people with severe liver or kidney disease, nor has long-term safety been evaluated. Cancer patients should not take extra phenylalanine and L-Tyrosine because these amino acids can contribute to cancer cell proliferation.

DMAE (Dimethylaminoethanol)
DMAE is a naturally occurring nutrient, found in sardines and other foods, that may help relieve depression and/or fatigue. A brain stimulant, DMAE passes through the blood-brain barrier into the brain, where it helps increase the levels of acetylcholine (a neurotransmitter that plays an important role in both mood and energy levels).

DMAE has been shown to elevate mood; improve memory and learning; and increase intelligence and is even more effective when taken with vitamin B5 (pantothenate). DMAE has also been used with great success in the treatment of attention deficit disorder (ADD) in children and adults.

Depression often manifests itself as fatigue. By directly increasing energy levels and through its ability to alleviate depression, DMAE attacks fatigue on two levels. In summary, this nutrient:

Increases physical energy
Decreases daytime fatigue and allows for more natural sleep at night
Is a safe antidepressant that elevates the mood
Increases the ability to learn (it can raise IQ while you are taking it)
Helps reduce "brain debris" called lipofuscin, thereby improving brain function
Increases longevity as measured in laboratory animals

KH3
KH3 is a European drug that inhibits the enzyme monoamine oxidase (MAO). Inhibiting this enzyme has helped many people to overcome depression, but many standard MAO-inhibitors can have several side effects. KH3 works without producing negative side effects. It is mild and inexpensive.

Depression Pg (1) (2) (3) (4) (5) (6)

These statements have not been evaluated by the FDA. These products are not intended to diagnose, treat, cure, or prevent any disease