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Depression

Depression can be a serious illness with many potentially serious consequences, and its treatment should always be prescribed and supervised by a qualified physician. The following is for informational purposes only, and should not be construed as, nor is it a substitute for, professional medical advice.

Depression Is a Common Manifestation of Stress

If you're depressed, you are not alone. Depression afflicts nearly 17% of all Americans in the U.S. for the length of their lives. Furthermore, depression is nothing to be embarrassed of or shy about; quite to the contrary: those afflicted tend to be more gifted and higher achieving than their non-depressed peers. Indeed, stress (i.e., the stress commonly associated with achieving people) is a consistent cofactor in depressed people. It is in relieving this stress that St. John's Wort and nearly every prescribed pharmaceutical anti-depressant achieves its anti-depressant qualities. It is important to note that stress is the same no matter how it manifests itself; it is because of this that anxiolytic drugs and herbs are able to relieve so many disorders - ranging from depression to gastric upset to use as weight control agents.

A Note On Environmental and Genetic Causes

Depressed patients' environmental stresses play a major role in their disease. Most of these influences are better addressed with a licensed psychologist, however a few obvious factors bear note. Low light levels, poor sleep habits, and poor diet can, in combination or singly, provide the necessary factors for inducing depression. A good first line of treatment that you don't need a prescription for is as follows: increased exposure to bright light (the brighter the better), good sleep habits (depressed people's sleep schedules tend to rotate clockwise; staying up later and sleeping in longer - don't fall into this pattern! You should also be sleeping in a dark room and waking up under bright lights), and a balanced diet - by "balanced" is meant 40-30-30; the 40-30-30 method balances good and bad prostaglandins, chemicals normally produced by the body, but which are highly influenced by the foods we eat and which have significant bearing on one's state of well-being.

It is suspected that depressed people's increased sensitivity to stress may also carry a hereditary component. Whether this is the case or not, is beyond the scope of this discussion, and not relevant to treatment anyway; one certainly hopes that investigation into genetic inheritance would yield results for future generations. For the remainder, we will concern ourselves with what to do if you are depressed and leave how it happened to the researchers.

Three Types Of Anti-Depressant Agents

• Tricyclics

• monoamine Oxidase Inhibitors (MAOI's)

• Selective serotonin Reuptake Inhibitors (SSRI's - we will also include the MSRI's, or Mixed serotonin Reuptake Inhibitors in this category, since it was through the same mode of inquiry as the SSRI's that they were developed)

A little on brain chemistry will help to understand the action of these drugs. The human brain is teeming with chemicals, in fact, if you look closely enough, it's all chemicals! Without getting into philosophical discussions, suffice it to say that it would appear to some that all thoughts and all emotions have their chemical counterparts that can be studied under the microscope. If you're not comfortable with this sort of reductionistic view of the psyche, relax, there is plenty we don't know and plenty of room for alternative or supplemental models of understanding. It is only that the method of inquiry currently being pursued by medical science is that of "isolate and tweak", which, so far has had its rewards.
 
Two of the major chemical players in the brain when it comes to depression, are neurotransmitters known as serotonin and norepinephrine. These neurotransmitters, like all neurotransmitters, work something like the way keys fit into locks. On the one side there's the neurotransmitter, or the key, and on the other the lock, known as the receptor site. Every neurotransmitter has a specific receptor site that only it, or chemicals with similar structures "fit" into. When a neurotransmitter is received at its' receptor site, information is transmitted, whether it's a feeling of well being (serotonin, norepinephrine, et. al.), euphoria (opiates, for example), pain (acetaldehyde - i.e., the chemical metabolite of alcohol that yields the infamous "hangover"), a rush of excitement (epinephrine, also known as adrenaline), or some other chemical information. Once a chemical is received it is eaten up by another chemical called an enzyme. Monoamine oxidase is one of these enzymes. Think of enzymes as performing a janitorial chore in your brain.
 
One by one, let's look at how these agents work:
 
Trycyclics are wide ranging in their action on the brain's neurotransmitters and for this reason are termed "dirty". This is not "dirty' as in "bad" or containing dirt, but unselective in the brain chemicals that they affect. They affect the re-uptake of both serotonin and norepinephrine, allowing these two chemicals to hang around longer and do their thing before they are eaten up by the enzymes. Tricyclics also affect other brain chemicals, but for simplicities' sake, we will only address serotonin and norepinephrine.
 
MAOI's, as their name implies, work on the "lock" side of the reaction, by blocking the action of the monoamine oxidase, the enzyme that eats serotonin and norepinephrine. By blocking their reuptake, serotonin and norepinephrine are left to work their action for longer periods of time (MAOI's vary in their ability to block MAO, there is usually enough left to eventually degrade the neurotransmitters, it only takes longer). The problem with MAOI's is that they leave the brain open to the action of other chemicals (other amines) as well, not just serotonin and norepinephrine. This means that a person taking an MAOI has to avoid certain sources of otherwise harmless chemicals. These sources unfortunately include chocolate, aged cheeses, red wines, fava beans and many other commonly enjoyed foods. The repercussions of an accidental ingestion of these foods (actually, the tyramines they contain) while under the influences of an MAOI is staggering, and can range from hypertensive or hypotensive crisis to stroke and, possibly, death.
 
SSRI's, also as their name implies, affect only the reuptake of serotonin, and are thus considered "clean" in their action. They have proven quite effective in treating depression.

Undesired Side Effects

The main complaint with modern anti-depressant therapy is that of undesired side effects. The tricyclics are antihistiminic, which leads to dry mouth, hypostatic blood pressure (dizziness on standing from a relaxed position), constipation, urinary retention, carbohydrate cravings, excessive drowsiness, blurred vision and others. In short, the tricyclics are hard to tolerate, owing to these side effects. The MAOI's - well, if you can consider stroke a "side effect"... These aren't used often anymore. The best, the "clean", or specific drugs, the SSRI's, have a whole host of their own side effects as well: agitation, insomnia, loss of libido, and impotence are among them.
 
IF YOU ARE ALREADY ON ONE OF THESE DRUGS...
You should know that these side effects are not always present, and will almost always subside upon stopping the drug. Do not, under any circumstance stop your medication abruptly, or without contacting your attending physician! Do not under any circumstance mix drugs - and St. John's Wort is a drug.

Hypericin, Hyperforin and How St. John's Wort Works

Most studies on St. John's Wort were done on leaf standardized to 0.3% hypericin. This always was ONLY a marker compound - a reference or bench mark - to help control the studies and used by various pharmacopoeias in establishing guidelines. In other words, nothing antidepressant about hypericin itself has ever been established, although there is mounting evidence that hyperforin is a 5-HT serotonin reuptake inhibitor. Hyperforin is the second compound to have been identified from this plant and suspected as having antidepressant effects. Hyperforin is naturally present in St. John's Wort leaf in the amount of about 4% - no special process is needed to get this. This is why we have ALWAYS sold St. John's Wort standardized to 0.3% hypericin and supplemented with whole leaf (this insures nothing is left out, since we really don't KNOW what it is that makes this plant work). Initially it was thought that St. John's Wort's antidepressant effects were due to MAO inhibition - probably an incorrect hypothesis since the MAO inhibiting activity of St. John's Wort is minimal at best. We are left with the question, HOW does it work? Some interesting hypothesis have been proposed; here are two of them:

The Immune System Modulation Hypothesis

Cytokines are mediators involved in cell-to-cell communications. Interleukins are types of cytokines involved in hemopoesis (regeneration of red blood cells) and immune response. One of these is a protein called interleukin-6 (IL-6) (there are 12 known interleukins). IL-6 is also involved in cellular functions in the nervous system. Specifically, IL-6 activates the hypothalamic-pituitary-adrenal axis, resulting in increased production of Corticotropin-releasing hormone (or "CRH") - the hypothalamic peptide which stimulates corticotropin release from the pituitary gland. Increased production of corticotropin means release of adrenaline, which means STRESS! St. John's Wort has been demonstrated through in vitro experiments to greatly reduce the release of IL-6. This hypothesis has not been tested in vivo, but it is compelling because it provides a hypothetical link between St. John's Wort's known immune system and antidepressant effects.¹⁶

The SSRI Hypothesis

Simply put, there is a great deal of evidence accumulating that hyperforin selectively blocks the reuptake of serotonin.^3,4,9,14,17 If this is found to be true, what we will have is a naturally occurring SSRI - like Prozac! Studies have shown that hyperforin alone produces results comparable to that of whole St. John's Wort leaf.³ Another study compared St. John's Wort with differing hyperforin content and identical hypericin content.⁹ That with the greater hyperforin content came out on top.

What We Know

In the end, like the now obsolete MAOI hypothesis, neither of the above hypotheses may prove true - maybe both will; fortunately this has little impact on practical application. We know that it does work, and we know what methods of standardization produce the desired results. While we wait for the answer, any product that is standardized to 0.3% hypericin AND contains whole leaf should have a hyperforin content of about 4% and will work.

St. John's Wort Is Cost Effective

Users of St John's Wort enjoy the same or better level of relief from depression when compared to traditional pharmaceutical agents, but without the annoying side effects! They also save money. St John's Wort is comparatively cheap: one month's supply of Effexor at 75mg/day costs approximately $150, one month's supply of St. John's Wort, at an effective level, costs approximately $15. St. John's Wort offers a low risk and credible benefit at a low price.

The Safety of St. John's Wort

The safety of St. John's Wort as listed by the Botanical Safety Handbook¹², an industry guide published by the AHPA, and conservative in its recommendations notes that it "may potentiate pharmaceutical MAO-inhibitors". The German Commission E Monographs² notes that "photosensitization is possible, especially in fair-skinned individuals"; no contraindications are listed, nor are restrictions during pregnancy or lactation listed. The Herbal PDR⁷ notes that "no health hazards are known in conjunction with the proper administration of therapeutic dosages. The tannin content of the drug can lead to digestive complaints, such as feeling of fullness or constipation. Photosensitization has been observed in animals following intake of large quantities of the drug (starting at 3 g per kg of body weight, which would be 150 g for a person weighing 50 kg) (hypericismus). However, such a reaction is unlikely with administration of therapeutic dosages." The Textbook of Natural Medicine¹⁶ notes that "there have been no deaths due to St. John's Wort toxicity, a stark contrast to the 31 deaths per 1 million prescriptions produced by synthetic prescriptions." Most importantly, if you decide to take St. John's Wort, please discuss it with a qualified physician, you will be surprised at how receptive many physicians are to this remarkable herb.

Drug Interactions

The medical journal, The Lancet, has published a study that showed that a drug interaction has been found with St. John's Wort.⁵ The interaction is that of an inhibitory effect on a protease inhibitor called indinavir, which is used in the treatment of HIV. The Lancet also published, in the same issue, a study that showed that St. John's Wort may also stimulate the rejection of transplanted hearts.⁵ From this new information, scientists postulate that it is likely that St. John's Wort works along a metabolic pathway (particularly one involving the liver). THEREFORE, it may render such drugs as birth control less effective. If you are currently taking a drug that works along a metabolic pathway (your doctor will know), St. John's Wort may not be for you. Consult a physician.