Please bear with me... I’m going to use a fair amount of scientific terminology in this one!

No matter how depression originates, it always ends up effecting brain chemistry. And while changing one’s lifestyle and outlook can be invaluable, there is no doubt that taking supplements and/or drugs to modulate brain chemistry can also have powerful results.

There seem to be two basic types of brain chemicals (or “neurotransmitters”) involved in depression, both of which play their own unique roles in maintaining a good mood. On one hand, there’s serotonin. Serotonin-deficient depression is often characterized as an “agitated” depression, sometimes associated with anxiety, sleeplessness, compulsive actions including binge-eating, and aggression. And on the other hand there are the catecholamines (dopamine and norepinephrine). Catecholamine-deficient depression is often characterized as a “flat, low-energy” depression. It can sometimes be tied to loss of appetite, loss of sex drive, narcolepsy, and low blood pressure. Obviously, these are all general guidelines, not rules set in stone. Once again, I’ll refer you to the book Natural Prozac, by Joel Robertson and Tom Monte, for its wonderfully clear and informative descriptions of serotonin- and catecholamine-deficient depression. There’s even a questionnaire to help you determine which type you are.

As you read this, bear in mind a few things. First of all, vitamin B-6 is necessary to make every single one of these neurotransmitters. You can increase the efficiency of any neurotransmitter precursor by taking B-6 along with it. Bear in mind as well that although these treatments may sometimes work literally overnight, they often take 1-2 weeks. Finally, amino acids are components of protein. Usually, when you take an individual amino acid, you want to take it away from protein foods so it doesn’t get “lost” in the wash of aminos released after a meal. That being said, make sure to get enough protein in your diet! A few eggs for breakfast, or a whey protein shake can sometimes be invaluable.

Serotonin Precursors: 5-HTP. We make serotonin in our bodies from a compound called 5-HTP (5-hydroxytryptophan). But before that can happen we must make 5-HTP from the essential amino acid tryptophan, present in our food. It’s this first step of making 5-HTP from tryptophan which holds up the entire process, and it gets even slower if we are under stress, have type II diabetes, or are deficient in magnesium or vitamin B-6. By taking 5-HTP as a supplement itself, we bypass this first step, making it a lot easier for our bodies to make more serotonin.

A recent article in Alternative Medicine Review states “Since the early 1970s, at least 15 studies have evaluated the clinical effects of 5-HTP on depression... taken together, these studies examined a total of 511 patients with different types of depression. Of these 511 subjects, 285 (56%) showed a significant improvement while taking 5-HTP.” In many of these studies, the 5-HTP was just as effective as the prescription drug that it was being compared to, with a quicker response time, and much fewer side effects. While a 56% success rate is pretty good, I think that number should actually be higher. To begin with, some of these studies included seriously depressed patients, people who usually don’t respond well to any one drug. Some of them even included patients with bipolar disorder, for whom 5-HTP is not recommended.

5-HTP can is also useful at controlling food cravings, especially for carbohydrates. It also can be used to help people get to sleep. It also helps some people with migraines.

Unlike other amino acid supplements, 5-HTP can be taken with food. I’ve seen dose recommendations range anywhere from 50 mg to well over 1000 mg a day. Although 5-HTP is considered to be very safe, I’d be hesitant to use the much higher doses without a doctor’s supervision. The Encyclopedia of Natural Medicine suggests 100-200 mg, three times a day. On the rare instances when people do run into problems, they tend to be your basic run-of-the-mill digestive stuff like mild nausea, stomach upset, heartburn, etc., that go away when they stop taking it.

Catecholamine Precursors: Tyrosine and Phenylalanine. Tyrosine and Phenylalanine are both precursors to the catecholamines, just like 5-HTP is a precursor to serotonin. But while the research on 5-HTP as a serotonin precursor is fairly compelling, that on the catecholamine precursors is not. There have been few studies, with mixed results. One of the reasons 5-HTP can be so effective is that it lets you bypass the rate-limiting step of serotonin synthesis. With tyrosine and phenylalanine, however, the rate-limiting step is still ahead of them. I have known a few people over the years who have sworn by tyrosine and/or phenylalanine, but they were in the minority.

With that, if you fit the description for catecholamine deficiency, tyrosine and phenylalanine are worth a try. They can still be useful, especially in situation where the precursors tend to be depleted, such chronic stress or alcoholism. A number of clinicians report that they are quite useful in keeping recovering alcoholics sober. Also, in those instances when depression is combined with narcolepsy, tyrosine has been shown to be remarkably useful.

SAMe: the best antidepressant in the world? SAMe is versatile enough to help the body make more serotonin and catecholamines, as well as other important compounds such as glutathione (the number one antioxidant in the liver) and coenzyme A. For many, it is the ideal all-around pick-me-up. Personally, the feedback I’ve gotten on SAMe has been very, very, very good. Certainly, I have never had as an enthusiastic response for an antidepressant. Now here’s what the Life Extension Foundation Disease Prevention and Treatment manual has to say about this supplement:

“The safest and most effective antidepressant in the world is the European drug S-adenosylmethionine (SAMe). SAMe is a simple natural metabolite produced from the essential amino acid methionine... It is found in every cell within the body and plays an important role in critical biochemical processes... When compared with other antidepressants, SAMe works faster and more effectively, with virtually no adverse side effects. In fact, unlike FDA-approved antidepressants that have both lethal and nonlethal side effects, SAMe produces side benefits, such as improved cognitive function, protection of liver function, and a potential slowing of the aging process. Some people take SAMe for its antiaging properties alone.”

The book goes on to summarize almost a dozen studies where SAMe was compared to both placebos and other drugs in a variety of different conditions, in a variety of depressive states. We have a reference copy of this book which you are more than welcome to come in and take a look at.

The major drawback with SAMe is the price. SAMe is expensive to make and expensive to package right, although the price has come down over the last two years. Then you look at the doses used in the studies, which generally fall into the 800-1600 mg range... SAMe can be more expensive than Prozac! And when I said earlier that I’ve been getting “very, very, very good” feedback, I was referring to the people I’ve spoken with who were taking at least 800 mg a day. Obviously, not everyone needs to take that much, and I’ve also spoken to people who’ve done well on a lot less. Most recently, a coworker of mine says a friend of his is doing great on just 400 mg. This will be up to you.

Can you combine these supplements with prescription antidepressants? Well, yes and/or no... Amino acid precursors do not interact directly with prescription antidepressants. SSRIs like Prozac, Zoloft, and Paxil work by keeping serotonin around longer once it’s been made. MAOIs do a similar thing with catecholamines. As you can imagine, combining precursor therapy with prescription antidepressants could be quite effective at combating depression. And indeed, a number of studies have reported positive results doing just that.

It is possible, however, to “overload the brain” this way, leading to occasional serious side effects. It all depends on what dose you’re using, which antidepressant you’re on, and your own individual biochemistry. The bottom line is this: despite the strong possibility of real benefits, especially in the more severe forms of depression, you should not combine the two unless you are working with a healthcare practitioner knowledgeable about both the prescription drugs and the supplements.

-Adam Stark