Understanding Depression

J. Raymond De Paulo Jr., M.D.

John Hopkins School of Medicine and Leslie Alan Horwitz
Copyright 2002
ISBN 0-471 39552-
Publishers: John Welsy and Sons
Pages 209 - 228

ECT, Light and Other Medical Treatments

pp 209

All along, I've been underscoring the fact that medications can alleviate about 65-70 percent of major depression within a two-month or two-year period. What about those who have gotten little or no help from these drugs? Several other treatments, some old and others new, are available and some have proven effective. I'll start by discussing one of the oldest treatments, which, while still regarded as controversial in the press it's actually used more today that twenty years ago.

Many years ago I was practicing at a large city hospital when I became aware of a pronounced thumping that reverberated throughout my office. It went on for days, but I didn't think anything of it because of the noise from a construction site nearby. I assumed the thumping was coming from pile drivers. Then one of the psychiatric residents popped into my office and said, "Ray, we've got a problem. That noise you hear is coming from a manic patient we've got in the seclusion room on the inpatient unit. She's so agitated that if we let her out she'd be injuring people. She's determined to get out-she's beating her arm against the wall and the wall is starting to come down." What's more, the resident went on, it seemed that she's bitten of a piece of her plastic bedpan and swallowed it. The resident was desperate; he didn't know what to do. Already she was on a huge dose of the most powerful neuroleptic we had, receiving over 200 mg when the usual dose was 3 to 30mg a day. "We've got to consider this a medical emergency," he concluded. When I later took a look at the seclusion for myself I discovered that the resident hadn't been exaggerating: the wall had been reduced to chicken wire and slats, and would have to be rebuilt.

The solution that suggested itself to me observing the wreckage was a treatment that has a long history but to this day carries an undeserved stigma reserved for leeches and dunking chairs; electroconvulsive therapy (ECT), otherwise known as shock treatment. Compared to medication and other treatments available to us, ECT is the most immediate and strikingly effective treatment for severe depression and mania. After giving her consent, the patient needed only two ECT treatments to get to a point where she could participate in group therapy, And she needed just another two and a half weeks to make a full recovery from the episode. The transformation, achieved by ECT, in this patient and others like her was a little short of miraculous.

How ECT Was Invented

As a treatment, ECT predates all antidepressants and lithium by ten to fifteen years. It owes its origins to a Hungarian psychiatrist named Lazlo Meduna, who theorized that epilepsy and psychosis were incompatible; that is to say that people who had epilepsy has some natural protection because of their illness against the delusions and psychotic episodes that are a central part of schizophrenia. So, Meduna reasoned, if you, if effect, "gave" epilepsy to people with schizophrenia or other mental disorders by inducing seizures in them, you might relieve thier psychotic symptoms. His theory was mistaken on a number of counts. First of all, epilepsy does not provide protection against schizophrenia, nor did convulsive therapy prove very affective in schizophrenia either. However, as is done with most new treatments in medicine, a variety if patients were tested on it. Two groups if patients showed marked beneficial responces-those with severe depression and those with mania.

At first Meduna employed inhaled camphor, a naturally deprived compound, to trigger seizures. But these seizures were difficult to control once they started. Injections of another drug that was also capable of inducing seizures presented the same problem. Then two Italian researches-Dr. Lucio Bini, a psychiatrist, and Dr. Ugo Cerletti, a neurophysiologist-began to use electricity to produce seizures, they discovered were both effective and safe and could be easily controlled.

Up until their discovery of the value of ECT, the two scientists had been trying to determine whether epilepsy caused the brain damage during the seizures or whether the occasional obstruction of the airways during a seizure was responsible. The results of the Italians' research showed that while the shocks themselves caused no brain damage they did have a calming effect on both the animals and the humans they tested. To stop the flow of the current all they had to do was remove the electrodes placed on the forehead. Like Meduna, they found that patients with the most severe forms of depression and mania experianced a relatively quick recovery once they underwent treatment. The early forms of ECT, however, carried some risks that have been reduces by modern methods of anesthesia and advances in electronics.

Before anesthesia was used, a few of the patients sustained fractures of their limbs or vertebrae during ECT treatment. With anesthesiam howeverm fractures are almost unheard of and compression fractures if vertebrae have dissappeared except among aged patients who might have osteoperosis ("brittle bones"). And perhaps just as reasurringly, patients now receive anesthesia during ECT and so they don't feel a thing under ECT.

How Much Memory Is Lost After ECT?

Memory loss is another concern of ECT. One form of memory loss comes about in the immediate aftermath of the treatment when the patient is confused and disoriented but usually recovers in one to two hours. A more persistent type of short-term memory retrieval comes on slowly but also resolves more slowly, between one to six months. In any case, the first type of memory loss is largely due to the anesthesia rather than the procedure itself. Patients coming out of any surgery will experience the same thing. Actually, patients who have undergone ECT recover more quickly since they've been given less anesthesia to begin with. The second form of memory loss involves an inability to recall events that occurred just before and just after the treatment. This does not appear ordinarily until a patient has had four to six ECTs. The memory loss may extend a few months back; the loss is spotty and it's more intense the closer you get to the ECT time period. However, the memories might not be truly lost. "Misfiled" might be a more accurate term since they can be retrieved in large chunks by patients after ECT stops. Some patients may lose a degree of spatial orientation ability and find themselves confused if they get behind the wheel. This type of "loss" too, is usually transient.

There is yet a third form of memory loss: a temporary reduction in the patient's ability to learn new things. While the loss is often not noticeable either to the patient or the family, it can be detected by memory tests after three to six ECTs. At nine months after ECT, however, there are no detectable differences between the learning abilities of those who have undergone the procedure and those who have not.

Recent advances in asministering ECT have also helped reduce memory loss. Whereas in the past the electrodes were placed on both sides of the patient's head, equally good results have been attained when the electrodes are deployed only on the right, or nondominant side. Most patients benefit as much with this type of unilateral (one-sided) ECT as opposed to bilateral ECT. At the same time, researchers have succeeded in cutting down the amount of electricity per treatment and delivering it in a more concentrated way. By administering electric pulses, lasting no more than a fraction of a second, instead of in one large wave, the patient gets less current while still receiving the full benefit of the treatment.

A vivid account of whta transient memory loss after ECT is like comes to us from and English psychiatrist who received ECT while he was battling his own depression: "When an event, entirely forgotten, is brought to one's notice, it sounds completely strange, foreign and unknown. One has the felling that a confabulation is being presented: the details of the account seem unnecessarily elaborate.... Then a fragment of the story rings true; a name is recognized, for example, and a series of events or facts come suddenly to mind, in a linear sequence. One is suddenly aware of a curious faculty to feel one's way along the sequence, as one element leads to the next. The revelation has a marked quality of unreality.... Although it is a strange experience, it is in some ways quite delightful. It is as if one is seeing at least some aspects of life through new eyes."

He then proceeds to describe what it's like to experience a temporary loss of one's "map." "With the second course of ECT...my topographical schemata have become totally disorganized. I must look at a map to visualize the route from A to B, and I have forgotten completely the patterns that previously have been almost second nature to me."

And yet for this patient the ephemeral memory problems were well worth it given the outcome. "Whereas before treatment I became tearful with very little provocation and felt intensely sad out of all proportion to the stimulus, after on single treatment I was no longer crushed by my chance sadness. The troublesome symptoms of irritability also subsided early in the course of treatment."

There are also some physical side effects that can result from ECT about which patients should be aware. Frequently, it can cause headaches and muscle aches, especially in the jaw, that are probably attributable to the local dispersion of the current in the muscles of the face. And as with any surgical procedure, general anesthesia (the effect of which lasts only three to five minutes) poses some risk, with only a very slight chance of death. Twenty years ago the risk was about 3 in 100,000 treatment but that risk is probably less now due to recent significant improvement is anesthesia techniques and monitoring.

How Effective Is ECT?

About 80 percent of the patients who undergo the ECT procedure will do better after two to four weeks. They show a higher response than they would on medication. So why don't we use it for more patients? The reason is that ECT has demostrated effectiveness in the short-term. The rate of relapses, in the absence of medication, is fairly high. We're talking about a matter of months. As a result, almost alll patients who have recurrent depressions will need medications after ECT.

Whom do we consider the ideal patients for ECT in light of the patterns of benefit and risks? We recommend ECT for the most severely ill patients because they are less likely to respond to medications. A depressed or manic patient who needs to be in hospital because of delusions or intense suicidal thoughts would be a prime candidate for the procedure. Patients who refuse to eat and as a result may be at risk of dying of malnutrition or elso who depression or mania has aggravated an existing medical condition whould also benefit from ECT. The basic criteria for using ECT are:

Intensity of suffering

The risks inherent in the patient's condition

The likelihood of immediate success

ECT is also useful for severe mania as well as for depression, although we have more rapid-acting medicines for mania. In addition, it can be difficult for a doctor to gain the manic patient's trust and persuade them that he or she needs ECT.

How frequently is ECT used? At Johns Hopkins, for example, we may have as many a fifty or severely depressed patients on out wards at any one time; about 10 percent of them will receive ECT. It remains a powerful treatment with major benefits whose risks are both minor and relatively short-lived.

Why does electroshock therapy work? We don't know. The mechanism of therapeutic action is not understood. But there's some evidence from studies on animals, that ECT and antidepressants cause similar responses in their effects on neurotransmitter receptors and the activity of genes in specifiv brain regions.

Why Did ECT Get Such A Bad Reputation?

If we know ECT works for so many patients, even though we do not know how it works, why has it gotten such a bad reputation? Certainly the way in which it has been portrayed in many movies, particularly the Oscar-winning One Flew Over the Cuckoo's Nest, has instilled a fear of the procedure in people's minds. When I was a first-year medical student I also has the impression that ECT was outmoded and harmful, until one of my professors introduced me to a patient who was getting ECT. I witnessed firsthand the transformation of the patient from hopeless back to a relaxed caring person. That was all it took to shake of my bias, but I regarded it like all treatments for depression and mania-as a blessing even if it did have certaain drawbacks, such as being effective for only limited periods. Still, many patients recommended for ECT, especially for the first time, tend to believe the worst about it. It's very difficult to imagine yourself going through it. But when you're talking about medical procedures-a spinal tap, let's say-often aren't pleasant to watch in spite of the fact that both ECT and a spinal tap are very safe a pose little risk to the patients. ECT aslo acquired a tarnished image because of its overuse soon after it was introduced in the United States. It worked rapidly and effectively in many patients-and with few serious side effects even when it didn't work-that a few psychiatrists were impelled to apply it for almost all of their psychiatric inpatients. But as happens in so many instances, the pendalum swung too far in the other direction adn ECT almost disappeared from hospitals altogether. Since the 1980s, however, ECT has made a comeback and it is regularly used for the most severely depressed patients adn the occasional manic patient who doesn't respond to other treatments.

The apprehension with which patients look upon ECT is borne out in a recent survey conducted in England, showing that about 40 percent of patients approach the therapy with some degree of anxiety. But their attitude undergoes a sharp reversal once they've actually had ECT. In retrospect, 82 percent of the patients interviewed considered it no more anxiety-provoking than a dental appointment. More important, 78 percent said they were helped by the procedure and 80 percent stated that they wouldn't mind having it again if they needed to.

What happend, though, if ECT doesn't work? Does that mean that there's nothing more we can do for these patients? Quite the contrary. We have patients who fail ECT and yet who will respond favorably to the next medication we pull out of the box. There is a misconception the ECT is a last resort-treatment for depression.

Lifting Mood With Magnets

Someday it's possible, perhaps even likely, that electricity too, will no longer be needed to induce therapeutic seizures. That brings us to another, still experimental, treatment called repeated transcranial magnetic stimulation (rTMS). Like so many other treatments we've takled about, magnetic stimulation came about as a result of chance. In an effort to develop lighter and cheaper imaging machines to study the brain, researchers at the National Institutes of Health found that the small magnetic resonance imaging instrument created a sudden lift in a patient's mood when it was heldon the right side of the head. (When they experimented on the left side they found that the magnetic stimulation made patients feel depressed.) The use of magnetic stimulus to produce a localized magnetic field seems to produce at least temporary changes in mood. Since certain regions of the brain seem more implicated in depression and other in manias, these devices may one day make it passible to treat patients with a less potent but more precisely localized stimulation. Transcranial magnetic stimulation is also being studied as a way to perform convulsive treatment since a strong magnetic field can iduce seizure with many fewer side effects compared to electrical current.

Lifting Mood with Lights

Of all the therapeutic tools we have at out disposal, none could possibly be more economical, more low tech, or more easily accessible or convenient then bright lights. The use of bright lights to treat what has become known in the popular press as Seasonal Affective Disorder (SAD) came about because of the experience of a single patient. An astute observer of his own condition, he kept meticulous notes, recording the dates each year when he would be hit with a depressive episode. He proceded to share his observations with his doctor, who agreed that there was a definite pattern to his episodes: they invariably began to fall with diminishing sunlight and went away in spring. Though he was the first to bring the disorder to the attention of the medical community, he wasn't alome in his suffering from it. In the northern hemisphere SAD starts around mid-October; it is characterized by low mood, overeating, oversleeping, and a strong sense of lethargy. Although SAD moderates throughout the winter compared with other forms of depression, many SAD patients also have temorary very mild hypomania when they emerge from their depression in spring.

Light alone can make a substantial difference for many patients. However, many if not most of them find that a modest dose of and antidepressant (usually and SSRI like Prozac or Zoloft) is also very helpful at the same time. The standard daily treatment is 10,000 lux (the common measurement of brightness intensity denoted in terms of light candles) for thirty or sixty minutes per day during the darkest months. All you need to do is sit in front of the lights, so your eyes are within sixteen inches of them, to benefit from the treatment. (There's no need to look directly into the lights.) There are a few side effects, if any, associated with the use of bright lights apart form occasional headaches or a bit of agitation, which abates if the time spent in from of the lights is reduces somewhat. (Occasionally bright lights can also induce a mild hypomania.) If, however, you find yourself basking in the sun on Aruba in the middle of the winter you can probably do without bright light therapy for the duration of you sojourn.

Sleep Deprivation and Other Rare Therapies

The bright light story suggests that interfering with some natural cycles can have positive effects on mood. Another instance in which we can see something similar is when we deliberately deprive depressed or bipolar people of sleep.

The idea that there might be some therapeutic benefit in altering sleep paterns came from a German research group studying circadian rhythms. Circadian rhythms (the twenty-four-hour clock system wired into our brains) govern fluctuations in body temperature and the secretion of several hormones. In about two-thirds of patients with severe depressive illness, researchers notices a temporary improvement in mood if they were deprived of sleep during the night. The effect didn't persist, though, if they were allowed to take a brief nap in the morning. Subsequent studies show the optional results can be achieved if the patient is kept awake for the second part of the night, from two to six in the morning. But even if the patients remain awake throughout the next day the effect disappears when they sleep through the next night. Of course, there's a big trade-off here. By rousing themselves from sleep, my patients often temporarily alleviate their low mood but they're still going to feel groggy and irritable, as anyone would be when deprived of sleep. So obviously sleep deprivation as we currently do it is not going to be an answer to our prayers. We've also learned that sleep deprivation, like bright lights, often induces mania in bipolar patients. In fact, if they're already starting into a manic phase, they'll deprive themselves of sleep on their own. They may be one of the reasons mania seems to get worse so fast and lead to manic attacks. We could call this a feedforward machanism, a opposed to a feedback mechanism, in mania. You feel you don't need sleep, you don't sleep, and that in turn brings on an even more severe mania.

The findings about circadian rhythms and sleep deprivation, while not yet offering us and effective treatment, have given us a focus for research, allowing researchers to investigate specific aspects of brain function for their impact on mood. At this point we know more about how to study sleep than we do about how to study mood. We have now succeeded in "cloning" about seven genes that regulate biological functions in animals and in humans, making it more likely that we'll one day be able to control out body's clock for the treatment of depressive illness.

Rare Treatment Options:

Vagal Nerve Stimulation and Brain Surgery

Two additionasl therapeutic techniques, though seldom used, should be mentioned here. One is vagal-nerve stimulation and the other is brain surgery.

The vagal nerve occupies a crucial role in regulating gastrointestinal fuction. The nerve rund down part of the length of the spinal canal, culminating in the abdominal end of the stomach. In epileptic patients it has been found that stimulating this nerve-no one really knows why-has the effect of reducing the seizures in many patients. The procedure is not very different from inserting a pacemaker. A small loop of the vagal nerve is brought to the surface of the skin, and a stimulator is attached to it and covered over with a flap of skin. Some researchers feel that if vagal-nerve stimulation could help elileptics, it might also be able to help some people out of depression. Even as scientists look into the potential of the technique, most doctors would be reluctant to try it on their patients (unless a person has already had it done to treat epilepsy) because, however safe, it remains an inavasive treatment for major depression.

We have long wondered about why brian surgery in certain intractable cases of depression could result in a cure. By far the most common-and controversial-of these surgeries was prefrontal lobotomy, which involved removing much of the prefrontal lobe or else severing its connections to the rest of the brain. Introduced in the late 1930s, it was successfully employed as a means of controlling aggressive or violent behaviour and relieved some depressions. The procedure began to be used for many other causes of mental disorders-too much so. Unfortunately, because so much brain tissue was removed, a large number of patients suffered from a blunting of their personality. Like electroshock therapy, it proved to have enough lasting positive effects for so many patients that physicians began to overuse it. So it's understandable why lobotomies fell into such disrepute.

While prefrontal lobotomies had established that some surgical precefures did produce benefits, it wasn't until very recently that breain surgery has undergone reconsideration. It is now being used again, albeit with great caution and for only the smallest minority of patients. Recent improvements in mapping the brain have made it possible for surgeons to achieve their objectives whil destroying only an extremely small fractio of brain tissue. Since so little of the breain is involved in the surgery, there are few if any complications even if no benefit is achieved. The procedure, as carried out now, carries no danger of blunting personality.

Brain surgery remain extremely rare. I myself have seen only one such case out of eight thousand in my careerm but it was no less memorable for being rare. The patient, a young man, was totally disabled by his depression. He was hospitalized as many as twenty times a year. When all other treatment had failed, he underwent brain surgery at the recommendation of several doctors. For the first six weeks he did perfectly well; then he seemed to relapse, reverting to a state little better than he has been before the surgery. Naturally the patient and his family were devastated. But then he began to make steady progress again and now he's working as a full-time writer. He has been well for four years and has not needed to be hospitalized in all that time. It does appear as if the surgery resulted in a near complete cure.

The problem with a case like this, no matter how spectacular, is that you can't use it as a precedent. Because these cases are so rare there aren't enought of them to do a controlled study to determine how often surgery works and to what extent. Nor would I yet want to recommend surgery for many patients. While medications are improving and are much to be preferred over other current treatment options, advances in the use of techniques like ECT and brain surgery give me a good deal of confidence that we will have many new and perhaps unexpected ways of helping people with depression and mania in the near future.

Chapter 18

Alternative Treatments

pp 220

Many doctors noe advocate for patients to take responsibility for their own health but the rest of the medical profession has been slow to take up this common-sense idea. We doctors generally tended to act in an overly paternalistic way, prescribing drugs and procedures while consigning patients to a more or less passive role in their own treatment. Many patients, look for alternatives. In other cases they are so desperate that they turn to any source that offeres a solution even if it proves to be bogus. In its most limited sense, self-treatment can be as simple as a regimen of eating well and getting regular exercise. But self-treatment goes beyond nutrition and exercise. Today's so-called alternative or "natural" treatment include everything from herbs and nutritional supplement to chiropractics, acupuncture, and aromatherapy. Like many other "allopathic" doctors, I tend to react to each new alternative treatment I learn about with skepticism, at least initially. (Allopathy is defined as a system of medicine that relies on proven remedies for treatment.) To be sure, I am skeptical of all new medical treatments until they are shown to work. Alternative treatments, though, pose special difficulties and sometimes make for some contentious exchanges with patients or their families. By expressing any doubts about a treatment that they believe will work for them, all I am doing is reinforcing the belief in their minds that I am being close-minded. They lump me in with all those in the medical profession who either dismiss or condemn alternative treatments out of hand. In some sense that's how we came to call these alternative treatments in the first place. They are not the treatments that your doctor will prescribe. After giving the matter a great deal of consideration, though, I began to think that it might be possible to find some middle ground rather than viewing the situation starkly in terms of black or white.

Why Patient Seek Out Alternative Treatments

Before I did anything else, I needed to understand why so many patients seek these treatments, often in apparent disregard of their doctors' reservations, even though in the past their doctors may have enjoyed their unquestioning trust. Second, I has to understans why doctors are so skeptical to begin with. This represented a departure from my usual approach. I like to remind people that the first tenet of the Hippocratic Oath is "First do no harm." Doctors are paid to be skeptical of all treatments, no matter what we call them. Whether a treatment is standard, alternative, allopathetic, or experimental, each one must be carefully studied in terms of its risks and benefits before it can be approved for widespread use. But those are the concerns of doctors, researches and regulators. People who are suffering with serious illnesses have different motives and different needs and I understand there as well. On of the first things-and one of the most surprising, too-I learned when I started reading the literature on this subject was that most people who seek alternative treatments are not the patients who shun conventional treatments. In fact, just the opposite is true.

Basically, 10 percent of the U.S. adult population made at least one visit to an alternative practioner-including acupuncturists, chiropracters, and massage therapists-in 1994, the las year for which reliable statistics are available. It is now estimated that 42 million Americans seek out some form of alternative treatment. Surprisingly, the people who saw an alternative clinician also made twice as many visits to physicians as did individuals who did not see alternative practioners. These patients nonetheless reported that they had very high needs for medical care that weren't being met by any practitioner. It would seem then that these are people who are very concerned about their health. However, it would be a mistake to assume that they are consumed by hypochondria or excessive worrying.

In one study of patients who were receiving care in a melanoma clinic in Austria, 14 percent (or 30 out of 215) sought alternative treatment compared to another 54 percent who, while reporting interest in alternative treatment, never sought them out. Melanoma is a serious, potentially fatal form of skin cancer. Those who sought alternative treatment had more advanced melanomas than those who did not. They study also showed that those who expressed interest in alternative treatments but never sought them were, as a group, younger and had more active coping styles compared to those who had no interest in alternative treatments. What's more, this group of the "interested" also displayed a marked propensity to search for personal or religious meaning in their disease. Nonetheless, all three groups-those who received alternative treatments, those who were interested in them but never acted, and those who wanted nothing to do with them-did not differ in either their faith in their doctors or in their compliance with controversial treatments. But the patients who did express interest in alternative treatments were virtually unanimous in their feeling that they weren't getting the attention they'd hoped for from their physicians. Many of them were especially concerned that their treatments weren't working, an understandable worry in patients with advanced melanoma. One thing that this study demonstrated was that it wasn't so much the type of treatment per se that made alternatives attractive, but the attention and the sense of shared hope that the patients felt they were receiving from alternative treatment providers. On the average, alternative providers spent longer with each patient, administered more treatments themselves (rather than relying on the nurses or technicians), and by and large prescribed fewer medications than the average medical corporations, which encourages psychiatrists as well as other physicians to see patients for very short visits, alternative treatments represent a much more patient-friendly picture.

What Exactly Is Natural?

If you walk into a store specializing in nutritional supplements and herbs, you will find an astonishingly large number of them on the shelves. Some, of course, are better known than others and as a result of their popularity have stirred some interest in the psychiatric profession. These include St. John's Wort, SAMe, DHEA, omega-3 fatty acid (fish oil), and L-tryptophan. Since I get so many calls from friends and professional colleagues about these treatments, I'm always looking for studies comparing them to standard treatments or to placebo. I'm also looking for studies that ask, "Well, if this woeks for something like depression, then how does it do it?" What strikes me about the advertised benefits for these herbs and supplements is that they are supposed to alleviate anywhere from eight to twenty differenct conditions each. St. John's Wort, which was believed to have some antidepressant effects, is also said to promote would healing, and cure skin diseases, various cancers, AIDS, and lung and kidney disease. That doesn't sound like a sensible set of claims to me. Pharmaceutical companies couldn't make so many claims for their products because the Food and Drug Admistration (FDA), which has control over the claimes they can make, wouldn't allow them to without substantial proof to back them up. However, since 1994 these supplements have not been under FDA control because they are considered neither drugs nor food. I know that many herbs have been in use for centuries and, though argumentable. that most of them are generally quite safe.

But there's another argument about safety, which hinges on the definition of the term natural. Nerither the FDA nor any other regulatory or medical body has and acceptable definition of natural that any company marketing an alternative substance would have to adhere to. I would point out that arsenic and cyanide are natural, too. And poisonous mushrooms are very natural. The most controversial treatment for bipolar disorder is natural: lithium is a salt derived from the earth.

There is another argument that advocates of alternative treatments advance, which goes like this. The FDA will approve only drugs that have been rigorously tested in both animals and human beings and are found to be safe and effective. But drug companies, which spend billions of dollars to do research and produce these drugs, have no interest in testing nutritional supplements or herbs because they are "natural" and so can't be patented, depriving them of future profits.

As it turns out, this perception is quite mistaken. First, theses are very profitable products. They command a very high retail price and are much in demand. In addition, pharmaceutical companies are very interested in these products. They have bought many of these nutritional supplement companies. So while the label on the bottle if ginseng or gingko might look like it was printed in the back room, you might end up buying a product that is marked by Pfizer or Roche Lab. There may be a silver lining to this buying binge. Once makers of these supplements and nutrients come under the control of big pharmaceutical companies, they will probably have to institute more uniform quality control to avoid lawsuits.

When Supplements and Herbs Can Be Dangerous

One of the big problems we face is trying to discover what actually goes into the contents of a particular substance. You may read that a bottle contains gingko, a Chinese herb said to improve memory, but there's no guarantee that that's what's inside, or whether there might not be other ingredients in addition to gingko. In one study, it was found that something on the order of one-third of the bottles being sold in nutritional supplement stores were adultered with substances not listed on the label. In some cases, substitutions were made or there was less of what you probably thought you were getting. Many of these substances are diluted and the study found little standardization of concentration. Sometimes ingrediants that are added to these herbs or nutritional supplements have dangerous side effects. When researchers examined some bottles of gingko for their study, for instance, they discovered significant amounts of drugs that could raise blood pressure.

Luckily, most herbal remedies are relatively inert: they don't interact with the body and so they are almost perfectly safe even though they haven't been subjected to controlled human studies. However, when patients take them in addition to antidepressants or other prescription medicines, they may put themselves at risk for dangerous drug reactions. That's why I always encourage my patients to be honest with me and let me know whether they're using supplements or herbs. As we know, though, many patients are embarrassed to admit that they're doing anything of the kind. The result is that the doctor misses out on important information.

Let us take a closer look at some of the most popular supplements and herbs on the market that are reputed to have therapeutic value for depression and manic depression. A word of caution: what is called an alternative treatment has a way of changing quickly. So I will confine my discussion to those substances that enjoy popularity as of this writing. But, as they say in the fine print of ads for airline tickets, everything is subject to change without notice.

St. John's Wort

The best known herbal treatment for depression today is St. John's Wort. It is also the best studied of all the herbal treatments with antidepressant claims. Known to botanists by its Latin name, Hypericum Perforatum, it's an attractive yellow flower (weed might be more appropriate) that grows in warm to moserate climated including the southeastern United States. Taken alone, it is safe and has few side effects at recommended dosages. In fact, I have found more information about the toxicity of St. John's Wort in the agricultural literature than in medical literature. It seems that the occasional grazing cow cleared a field of the wild flower in the morning and got a very bad skin reaction when exposed to the sun. Recently there have been greater concerns about drug interactions in AIDS patients who take St. John's Wort and their anti-viral medications, but it is not clear how big this risk is. A recommended dose of 900 mg a day of St. John's Wort costs 30 cents to $1.50 per day (the cost of standard antidepressants runs 30 cents to $2 per day) and I have friends who have sent me cans of tomato soup and teas fortified with it. In 2000 American spent $195 million on the pill form of the herb. About twenty patients have seen me while they were taking it but I couldn't be confident whether it was helping them or not. Most of them said thay were taking it because it might help, and that they sensed that since it is an over-the-counter "natural supplement" that they could do it on their own. Most of them had no idea that becuase of its recent popularity, large pharmaceutical firms manufacture and sell it.

The early studies of St. John's Wort (23 of them) were done in Germany in the early 1990s. These studies concluded that the herb was more effective than placebo and equally as effective as standard antidepressants in treatment of mild to moderate depression. Isn't that enough? Not really. Unfortunately, the studies do not include a standardized diagnostic evaluation so we could not compare the diagnostic groups and that severity of the group of patients compared to the patients in trials of other drugs as possible antidepressants. They provided some information on the condition of the patients before they entered the study. The patients had depressive symptoms and in addition we know their age, sex, and score on a depression scale. Did the patients have major depression? Some did but it is not clear how many. Other standradized random clinical trial procedures may have been rigorously followed, but in most of the early studies I couldn't answer these questions because they are not included in the papers. Another problem is that the doses of antidepressants administered in the study for the sake of comparison were dosages that were too small. The doses given, in fact, wouldn't have been expected to be any more effective than placebo treatments.

In May 2001 the changed, the Journal of the American Medical Association (JAMA), published the results of a large U.S. multicenter study of St. John's Wort. This study was by far the most rigorous one done to date. The findingd weren't very promising for advoctes of the herb, than a plecebo tablet. But another study of three hundred patients is still being analyzed at the time of this writing. Unless the result form that study is more hopeful, we'll have to conclude that St. John's Wort is not an antidepressant, at least not for major depression.

DHEA

DHEA (short for dehydoepiandrosterone) is a naturally occurring substance in the human body. Present in small amounts, it is known as a prehormone or a precursor to testosterone. It is known to have potentially serious medical and psychiatric side effects based on its relationship to testosterone and other steroid hormones. It is banned by many sports authorities (swimming and biking), but the FDA doesn't regulate it and Major League Basball used to permit its use. This was of more than a passing interest because Mark McGwire's motivation in taking it. Does it have any effect on depression? A number of years ago some researchers published a few very small but inconclusive indications that DHEA might help the performance of other antidepressants. While researchers found no proof that it doesn't have any effect, they found no proof that it did. What is perhaps more revealing of their of DHEA is that they stopped using it for depressed patientis in their research programs. DHEA is extremely expendive ranging from $17 to $42.50 per 400 mg pill. The most common side effect is menstrual irregularity. But some severe mixed or manic states have been suspected to be related to DHEA.

SAM-e

Recently wide attention has been given to SAM-e. Several books have come out in recent year promoting SAM-e as a "natural" cure for depression. SAM-e (short for S-adenosylmethionine, which naturally occurs in humans and in other organisms), was first discovered in 1952 and has been commercially available in Europe since the 1970s. An amino acid that acts as a catalyst in a number of metabolic reactions, it is involved in the manufacture of joint cartilage and the maintenance of neural cell membrane function. It was thought that perhaps it might be a useful treatment for some psychiatric disorders based on the old theory that schizophrenia and possibly depression were related to levels of methionine in the blood. If you read the promotional literature for SAM-e you'd think the substance has been thoroughly tested. Her, for example, is a pitch from on distributor of SAM-e: "The reason behind much of the attention being paid to SAM-e is the significant amount of scientific evidence supporting its use. There are over 75 clinical studies on SAM-e worldwide, involving thousands of people that appear in scientific publications. One respected medical journal published a very positive collection of studies on SAM-e totaling over 100 pages." To the uninitiated, all this might sound very impressive, but in fact, while some of these studies in the 1960s and 1970s suggested that SAM-e might be a useful antidepressant, they failed to demonstrate any clear benefit. The studies were not vigorously done and the research stopped, and although some individuals in these studies clearly got better, we cannot say that they did any better on the SAM-e that off it. Again, there is no proof of ineffectiveness, just an absence of proof that it has any effect at all.

Omega-3 Oils

Dietary difference between Americans and Japanese-characterized by a fondness for fatty food on the one hand and for figh on the other- have long been though to be a possible explanation for the lower reated heart disease and gastric cancer in Japan. As researchers began to study the therapeutic benefits of a diet rich in fish, they found some evidence that fish omega-3 oils might also be a possible treatment for depressive illness. It has been noted that people with depression have lower cholesterol levels than other people do.

While the Japanese eat a lot more fish on a regular basis than the average American does, it isn't clear that Americans have more depression than the Japanese. Some studies duggest a small difference in rates. Even if the small differences reflected real differences in disease rates, though, that doeasn't mean that diet had to be the cause. Nonetheless, some studies are now going on to find out whether omega-3 oils may if fact hold some promise in treating depression and so far one has indicated that it might be helpful. We will keep but we will maintain the professional skepticism until the data is all in.

The Business of Hope

In addition to these herbs and supplements, you can find all kind of other alternative treatments supposedly useful for depression ranging from acupuncture and astrology to aromatherapy, yoga, and medication. Now, just because there is no good evidence that any of there practices work, we shouldn't discount the potential power of placebo. If we can get more people wuth moderate depression to come forward for treatment because they're interested in trying alternative treatments, their experience may turn out to be very therapeutic, especially if the treatments are less toxic and less expensive than standard medication. Again, though, we have to emphasize that for people who have severe depression these alternatives are unlikely to do as much good as proven antidepressants, therefore I always recommend an initial evaluation to establish a correct diagnosis.

How do I react when a patient comes into my office and tells that he or she has been taking St. John's Wort or seeing an acupuncturist? Well, to be honest, my reaction over the years has changed. On the one hand, the skeptic in me still comes out very quickly (though I'm discreet enough to bite my tongue). On the other hand, my reaction is now usually tempered by the notion that most of these treatments are fairly safe in terms of pharmacology. That, of course, is both their greatest strength and their greatest weakness. As I said, most of the herbs and supplements on the market are pretty inert in terms of their effect on physiological systems (though there are exceptions). What concerns me most about patients resorting to alternative treatments is whether conventional treatment is failing them. What exactly are they looking for? The illness may be so severe and recovery so slow or imperceptible that they may have lost faith that we have all the answers. That certainly is a legitimate concern. What we want to do is get patients to air their feelings honestly so that we can discuss treatment and consider what options are available.

All the same, I must speak up as the skeptical doctor who is concerned about maintaing the proper balance between patients' needs and their hopes. Hope is probably the operative word here. If you want to look at medicine as a business, then the currency of our business in hope. And I'm talking about realistic, credible hope, not false or magical hope. My practice and advice is to use what is proven first, but never quit, so that if all "proven" treatments have been given fair trials then unproven treatment should be given a fair shake as well.

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