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More of us than ever are discontented and not experiencing optimum emotional well-being. Why is the vast enterprise of professional mental health unable to help us feel better?

An alternative to the old talking cure is expanding the knowledge base of psychotherapy as we recognize the role that exercise, nutrition, spirituality, mind-body approaches, and lifestyle can play in enhancing our clinical effectiveness. Epidemic depression is occurring at a time when the field of mental health appears very robust. There are more mental health professionals treating more people than ever before in history: psychiatrists, clinical psychologists, licensed social workers, counselors, and therapists of all kinds. We have a powerful "therapeutic arsenal" of drugs to make us happier, calmer, and saner. When I leaf through the pharmaceutical ads that take up so much space in psychiatric journals, I get the feeling that we should all be in great emotional health. Depression and anxiety should be as fully conquered as smallpox and polio. But more of us than ever are discontented and not experiencing optimum emotional well-being. What is wrong with this picture? Why is the vast enterprise of professional mental health unable to help us feel better?

I want you to consider the possibility that the basic assumptions of mainstream psychiatric medicine are obsolete and no longer serve us well. Those assumptions constitute the biomedical model of mental health and dominate the whole field.

In 1977, the journal Science published a provocative article titled "The Need for a New Medical Model: A Challenge for Biomedicine." I consider it a landmark in medical philosophy and the intellectual foundation of today's integrative medicine. The author, George L. Engel, M.D., was a professor of psychiatry at the University of Rochester (New York) School of Medicine. Determined to overcome the limiting influence of Cartesian dualism, which assigns mind and body to separate realms, Engel envisioned medical students of the future learning that health and illness result from an interaction of biological, psychological, social, and behavioral factors, not from biological factors alone. He fathered the field of psychosomatic medicine and devoted much of his career to broadening our understanding of disease. He was particularly interested in mental health.

George Engel died in 1999 with his vision largely unrealized. In fact, the field of psychosomatic medicine ran out of steam sometime before his death and was never able to challenge the ascendancy of biological medicine.

"Biology Explains All" was in full swing when I was a student at Harvard Medical School in the late 1960s. At that time, I was taught that just four diseases were psychosomatic: peptic ulcer, rheumatoid arthritis, bronchial asthma, and ulcerative colitis. Four out of the entire catalog of diseases is not a lot, but at least for those four, doctors conceded that mental/emotional factors played a role. Peptic ulcer was knocked off the list in the early 1980s when a bacterial infection (Helicobacter pylori) was identified as the "real" cause of ulcers, now treatable with antibiotics. Investigation of biological factors associated with the three remaining conditions has led to more powerful drug treatments for them and greatly lessened interest in attending to any psychological, social, or behavioral factors that might be involved. Rheumatologists today, for example, are most enthusiastic about a new class of immunosuppressive drugs called TNF-α blockers, which often appear to put rheumatoid arthritis and ulcerative colitis into full remission. Never mind that these drugs can be highly toxic and are very expensive; once doctors prescribe them for these conditions, they no longer see the point of addressing emotional or lifestyle factors of the patients who have them.

Although George Engel's efforts in psychosomatic medicine were ahead of their time, their relevance today is great, and I advise all health professionals, especially mental health professionals, to read his 1977 paper in Science. I will summarize his "challenge for biomedicine" here, because it exposes the great limitations of the conceptual model that now dominates medicine in general and psychiatric medicine in particular. That model often fails to help doctors maintain and heal our physical bodies, and it has greatly hindered our understanding of and ability to manage the epidemic of depression and other mood disorders that plague our society. It does not point the way to contentment, comfort, serenity, and resilience, nor does it show us how to attain optimum emotional well-being.

Models are belief systems - sets of assumptions and explanations we construct to make sense of our experience. In Engel's words, "The more socially disruptive or individually upsetting the phenomenon, the more pressing the need of humans to devise explanatory systems." Disease is a very upsetting phenomenon, and humans throughout history have come up with a variety of belief systems to explain it, from the wrath of the gods to possession by spirits to disharmony with the forces of nature. The dominant model of disease in our time is biomedical, built on a foundation of molecular biology. As Engel explains,
"It assumes disease to be fully accounted for by deviations from the norm of measurable biological (somatic) variables. It leaves no room within its framework for the social, psychological, and behavioral dimensions of illness. The biomedical model not only requires that disease be dealt with as an entity independent of social behavior, it also demands that behavioral aberrations be explained on the basis of disordered somatic (biochemical or neurophysiological) processes. Thus the biomedical model embraces both reductionism, the philosophic view that complex phenomena are ultimately derived from a single primary principle, and mind-body dualism."
Engel goes on to say, "The biomedical model has . . . become a cultural imperative, its limitations easily overlooked. In brief, it has now acquired the status of a dogma. . . . Biological dogma requires that all disease, including 'mental' disease, be conceptualized in terms of derangement of underlying physical mechanisms." He proposed an alternative: a biopsychosocial model of health and illness.

There is no question that over the past century, biomedicine has advanced our knowledge of human biology, but the real test of a scientific model - the measure of its superiority to an alternative belief system - is whether or not it increases our ability to describe, predict, and control natural phenomena. In my books about health and healing, I have written a great deal about how strict application of the biomedical model has actually made it harder for us to understand and manage common diseases. For instance, I have pointed out that it fails to account for the fact that many people infected with H. pylori never develop peptic ulcers or have any symptoms at all. They coexist with it in a balanced way. Clearly, factors other than the simple presence of that germ play a role in peptic ulcer disease, including the strength or weakness of host defenses, of an individual's resistance. One of those defenses is stomach acid, whose production is influenced by the autonomic (involuntary) nervous system and through it by emotions. In the fight-or-flight response, the sympathetic division of the autonomic nervous system shuts down gastrointestinal function, which is unnecessary in an emergency, in order to divert energy and blood flow to muscles. That includes turning off the production of acid in the stomach. In chronic anxiety and stress, the sympathetic nerves are constantly overactive, and therefore there is constantly less acid in the stomach to keep potentially invasive germs from causing tissue damage. To say that H. pylori infection is strongly correlated with peptic ulcer disease is accurate. To say that it is the sole cause of ulcers ignores the complexity of causation and the possible influence of emotions.

In 1980, the American Psychiatric Association radically revised the Diagnostic and Statistical Manual - III (DSM-III) to be in accord with the biomedical model. As a consequence, the role of psychiatrists went from being facilitators of insight in patients to being dispensers of drugs to modify brain chemistry. Although some psychiatrists still rely on talk therapy, of all medical specialties, the profession as a whole is the most dominated and, to my mind, hobbled by blind faith in biomedicine. Psychiatrists were easily seduced because of a collective inferiority complex with regard to their place in the medical hierarchy. Still referred to as witch doctors and shrinks (from headshrinkers), they themselves have a history of questioning whether they are real doctors and whether they need the same basic medical training as cardiologists and surgeons. With the spectacular rise of biomedicine, their discomfort increased, and, not wanting to be left behind, they looked for ways to be even more biologically correct than their colleagues in other specialties. They saw their ticket to acceptance in the new and rapidly developing field of psychopharmacology - the study of the effect of drugs on mental and emotional disorders.

In 1921, Otto Loewi (1873 - 1961), a German pharmacologist, demonstrated that nerve cells (neurons) communicate by releasing chemicals. Prior to that time, neuroscientists thought nervous communication was electrical. Among the many important breakthroughs that followed from Loewi's work were the identification of neurotransmitters and the discovery of receptors on cell surfaces that bind them. Neurotransmitters are chemicals made within the body, stored in tiny sacs clustered within a neuron and released into the synapse, the gap between the neuron and a target cell, which might be another neuron (the postsynaptic neuron) or a muscle or glandular cell. The released molecules then bind to receptors - specialized proteins on the surface membrane of the target cell - causing changes in that cell, making it more or less likely to produce an electrical signal (in the case of a neuron), to contract (in the case of a muscle), or to secrete a hormone (in the case of a glandular cell). Later, the neurotransmitters can separate from their receptors and be taken up by presynaptic cells for reuse or be broken down by enzymes into inactive metabolites. Neuroscientists have now compiled long lists of neurotransmitters, described their actions, and identified many types and subtypes of receptors.

Three of the most studied neurotransmitters are norepinephrine, dopamine, and serotonin, all very relevant to the subject at hand because they influence our moods and emotions. For example, dopamine is involved in what is known as the reward system of the brain; drugs that affect it can alter our experience of pleasure. Cocaine is such a drug. It blocks reuptake of dopamine back into the presynaptic neuron, effectively increasing its action at the synapse to produce an intense pleasurable response. With prolonged use of cocaine, postsynaptic neurons become less responsive to dopamine, leading to depression and dependence on the drug to relieve it. The dopamine hypothesis of schizophrenia attributes psychosis to overactivity of this neurotransmitter. Norepinephrine regulates both reward and arousal. Disturbances in that neurotransmitter system are associated with anxiety disorders. And serotonin affects our moods and sleep.

The most widely used psychiatric drugs today influence the production and effects of these major neurotransmitters. Psychopharmacologists made their first big breakthrough in the 1950s from work with antihistamines, used to quell allergic symptoms. Although antihistamines are best known for blocking the effects of the compound responsible for certain immune responses, they also affect the brain, often making people groggy, sleepy, and depressed. By tinkering with these molecules, chemists produced a new class of psychoactive drugs - the phenothiazines - that blocked dopamine transmission. Thorazine and other phenothiazines were successfully marketed as major tranquilizers and antipsychotics and quickly revolutionized the treatment of schizophrenia. Psychiatrists hailed them as magical compounds that cured psychosis, while critics argued that they simply made psychotic people groggy, sedated, and easier to manage, even as outpatients. Energized by this achievement, psychopharmacologists then turned their attention to depression. Over the past sixty years, they have come up with a number of drugs to treat it.

The efforts of psychopharmacologists give us an opportunity to evaluate the usefulness of the biomedical model in psychiatry. In practice, psychiatric medicine today is synonymous with psychopharmacology. The credo of that field is "There is no twisted thought without a twisted molecule." (The words of the American neurophysiologist Ralph Gerard, 1900 - 1974). The biomedical model explains depression as the result of a chemical imbalance in the brain, specifically of neurotransmitters affecting our moods. How well does that explanation enable us to describe, predict, and control depressive illness? In other words, just how effective are the antidepressant drugs that psychopharmacologists have developed, that the big pharmaceutical companies sell such quantities of, and that so many people today take? The answer, I'm afraid, is not very.

The first antidepressant drug was discovered serendipitously in 1952. Iproniazid, an antimicrobial agent being studied as a possible treatment for tuberculosis, was found to affect mood, making even terminally ill patients cheerful and optimistic. Investigation of a possible mechanism for this unexpected psychoactivity revealed that the drug blocked enzymatic breakdown of all three major neurotransmitters: norepinephrine, dopamine, and serotonin. Pharmaceutical chemists then looked for other drugs with this action and soon after produced a different class of antidepressant drugs by modifying the phenothiazine tranquilizers. These became known as tricyclic antidepressants, of which amitriptyline was the prototype; Merck pharmaceutical company gave it the brand name Elavil. In 1961, the FDA approved Elavil for the treatment of major depression, and it quickly became a bestselling drug. The tricyclics appeared to work by blocking presynaptic reuptake of norepinephrine and serotonin without affecting dopamine.

Because all of the early antidepressants had unpleasant side effects and serious potential interactions with other drugs and medications, pharmaceutical chemists continued their search for better ones with more specific action. But what specific action should it be? Some thought deficiency of norepinephrine was the biochemical cause of depression. Others argued for a serotonin hypothesis of depression and looked for compounds to prevent its breakdown or reuptake. The proponents of the serotonin hypothesis would win the day; their big discovery came in the 1970s, again, interestingly enough, as a result of work with an antihistamine.

Very likely you have taken Benadryl (diphenhydramine) at some point in your life. It is one of the oldest and most widely used antihistamines, the first such drug to be approved by the FDA for prescription use, in 1946. Benadryl is so sedating that it is now sold over the counter as a sleep aid. In the 1960s, this tried-and-true drug was found to have an action independent of its effect on histamine: it selectively inhibited the reuptake of serotonin. By modifying this molecule, scientists at Eli Lilly and Company in the 1970s came up with the first safe and effective selective serotonin reuptake inhibitor, fluoxetine, much better known by its brand name Prozac. The rest is history. Today the accepted biomedical explanation of depression is that it results from a deficiency of serotonin at synapses in key areas of the brain; therefore, boosting the activity of this neurotransmitter with drugs that block its reuptake will treat or cure the problem.

It's a good bet that thirty years ago, not one American in a thousand had heard of this neurotransmitter - or any neurotransmitters, for that matter. Today, when you Google serotonin, about 11 million results appear, and Amazon sells nearly three thousand books with the word in the title (including The Serotonin Solution: The Potent Brain Chemical That Can Help You Stop Bingeing, Lose Weight, and Feel Great). "Serotonin" is the name of a professional wrestling team and an album by the British rockers The Mystery Jets. You can even proclaim your autumn blues to friends by way of a greeting card that reads, "The leaves and my serotonin levels are falling." A once-obscure neurochemical has become pop-culture currency, and increasing levels of this feel-good compound has turned into a public obsession.

None of this just happened on its own. In order to sell antidepressant medications, drug manufacturers launched a relentless worldwide marketing and public-relations campaign promoting serotonin as the distilled biochemical essence of happiness. The message was that selective serotonin reuptake inhibitors - SSRIs - increase synaptic levels of serotonin in the brain by slowing its rate of reabsorption by presynaptic neurons, ending depression. Psychiatrists and other physicians got the technical version of this message, while consumers got a simplified one, often reduced to the rallying cry "Boost serotonin!"

The only problem is that it probably isn't true.

Like the dopamine hypothesis of schizophrenia and other attempts to attribute complex mental phenomena to simplistic biochemical causes, the serotonin hypothesis of depression is shaky at best. Several studies have established that lowering serotonin levels does not negatively impact mood. In fact, a new pharmaceutical known as tianeptine - sold in France and other European countries under the trade name Coaxil - has been shown to be as effective as Prozac. Tianeptine works by lowering synaptic serotonin. As psychology professor Irving Kirsch of the University of Hull in England told Newsweek,
"If depression can be equally affected by drugs that increase serotonin and by drugs that decrease it, it's hard to imagine how the benefits can be due to their chemical activity."
It is, indeed, especially as evidence accumulates that, in most cases, SSRIs work no better than placebos to boost mood. The first such analysis, published in 1998, looked at thirty-eight manufacturer-sponsored studies that included more than three thousand depressed patients. It found negligible differences in improvement between those on the drugs and those on dummy pills. At least 75 percent of the benefit from this class of antidepressants seemed to be a placebo effect. This finding has since been confirmed by other research.

To say that biomedically minded physicians have been reluctant to accept this finding or modify their prescribing habits as a result would be a great understatement. Both professional and popular media have tried to play down the significance of this new research and in some cases have misreported the findings. In April 2002, the Journal of the American Medical Association (JAMA) published the results of a large randomized controlled study sponsored by the National Institutes of Health to evaluate a popular herbal treatment for depression, St. John's wort (Hypericum perforatum). Its effect was compared with that of the widely prescribed SSRI Zoloft (sertraline) and a placebo in 340 patients with major depressive disorder. The conclusion that made front-page news around the world was that St. John's wort worked no better than the placebo at relieving depression. Television news shows featured reporters in health-food stores pointing to St. John's wort products and advising consumers not to waste their money on natural remedies whose supposed benefits were nothing more than old wives' tales.

Never mind that St. John's wort is not indicated for the treatment of major depression, making the point of the study questionable. The finding from this well-designed trial that should have made front-page news was that Zoloft also worked no better than the placebo. In fact, the placebo treatment was actually more effective in these very depressed patients than either Zoloft or St. John's wort!

Irving Kirsch summarized the growing body of evidence against SSRIs in his 2010 book, The Emperor's New Drugs: Exploding the Antidepressant Myth, which I recommend. In response, proponents of the drugs and the serotonin hypothesis retreated to a more defensible position: SSRIs may owe much of their apparent benefit to patients' belief in them, they admit, but they still have a real biochemical effect that makes them useful in the treatment of severe depression. Unfortunately for those proponents, the most recent analysis, published in the January 6, 2010, issue of JAMA, rates the real biochemical effect of SSRIs as nonexistent to negligible even in most cases of severe depression. Only in patients with very severe symptoms can researchers detect a statistically significant drug benefit compared with that of a placebo. About 13 percent of people with depression have very severe symptoms. One of the authors of the JAMA paper, Steven D. Hollon, Ph.D., of Vanderbilt University, has said, "Most people [with depression] don't need an active drug. For a lot of folks, you're going to do as well on a sugar pill or on conversations with your physicians as you will on medication. It doesn't matter what you do; it's just that you're doing something."


I would argue that the dismal performance of Prozac, Zoloft, Paxil, and other antidepressant drugs relative to placebos not only leaves the serotonin hypothesis of depression without a leg to stand on but also exposes the failure of the biomedical model to further our understanding of and ability to manage emotional disorders. I firmly believe that the nature of depression will never be revealed solely in studies of brain biochemistry that are isolated from the rest of human experience. Like coronary heart disease, depression is a multifactorial health problem, rooted in complex interactions of biological, psychological, and social variables, best understood and managed through a broader biopsychosocial model of the sort proposed by George Engel.

Loneliness, for example, is a powerful predictor of depression. Numerous studies show that people with few intimate social contacts are more likely to be depressed than those who enjoy a rich network of friends and family. Reductionists might argue that being part of a social group boosts serotonin, but I am confident that there is something in a successful social life that transcends any effect on brain biochemistry, at least insofar as we currently understand that biochemistry. In other words, a happy family life probably raises serotonin in some people, lowers it in others, and leaves it unaffected in still others. Yet it makes them all more comfortable, serene, and relatively immune to mood disorders through a body-mind-social interaction that can't be reduced to its constituent parts.

The New Model

I have written about possible causes of epidemic depression in our society, among them such lifestyle factors as diets high in processed foods, lack of physical activity, social isolation resulting from affluence, and altered brain activity from information overload. In its narrow focus on molecular biology, the biomedical model fails to capture any of this, and practitioners under its spell cannot give depressed patients the advice they need to address the complex causes of their problems. All they can do is dispense drugs that for the majority of patients might as well be sugar pills.

In an effort to give mental health professionals more and better options, I convened the first national conference on integrative mental health in March 2010. Together with Victoria Maizes, M.D., executive director of the Arizona Center for Integrative Medicine, I invited psychiatrists, psychologists, social workers, and other health professionals to attend a three-day event in Phoenix to "learn how to treat their patients within a new paradigm of integrative mental health care that utilizes scientifically proven alternative methods in combination with drugs and traditional therapy to address patients' physical, psychological, and spiritual needs." The use of the word spiritual here is significant; it expands George Engel's concept to include yet another dimension of human life, one often overlooked in medicine. Adding it creates a biopsychosocialspiritual model. For convenience, I prefer the term integrative to describe this new way of thinking about health and illness in general and mental health in particular.

Dr. Maizes and I invited leading practitioners and researchers to share their experience and findings with attendees. We planned for an audience of three hundred, but, in a time of great economic recession, the conference sold out six weeks in advance with a total of seven hundred registrants. If we had had a larger venue, we could have doubled that number, so great was the interest in the topic - evidence, I think, that professionals are even more fed up than patients with the dead end that the drug-only approach represents.

On the closing day of the conference, I spoke about the failure of the biomedical model and the great advantages of the new integrative model of mental health. I quoted Albert Einstein on the subject of conceptual models:
"Creating a new theory is not like destroying an old barn and erecting a skyscraper in its place. It is rather like climbing a mountain, gaining new and wider views, discovering unexpected connections between our starting point and its rich environment. But the point from which we started still exists and can be seen, although it appears smaller and forms a tiny part of our broad view gained by the mastery of the obstacles on our adventurous way up."
The new integrative model of mental health does not ignore brain biochemistry. It takes into account correlations between imbalances in neurotransmitters and mood disorders. Nor does it reject psychopharmacology. Integrative treatment plans for depression, particularly for severe depression, may well include medication, but my colleagues and I prefer to try other methods first and to use antidepressant drugs for short-term management of crises rather than rely on them as long-term solutions. One of the invited speakers, a noted expert on psychopharmacology, gave an optimistic presentation on psychiatric drugs of the future, drugs that will have more specific, better-targeted actions. People listened to his lecture with interest but showed much greater enthusiasm for talks on the critical importance of dietary omega-3 fatty acids to optimum emotional health and the latest neuroscientific evidence for the benefits of meditation, among others.

To say that the psychiatrists, psychologists, and other mental health professionals in attendance appreciated this larger perspective fails to convey their excitement. One told me that she had been waiting years for such a conference. Another said he would take the information he received and use it to change standards of practice in a large group of mental health care facilities in his state. Many expressed interest in seeking formal training in integrative mental health, training that I and my colleagues at the University of Arizona hope to provide.

Presentations that particularly interested me concerned neuroplasticity, the potential of the brain and nervous system to change and adapt. The speakers were neuroscientists influenced by Buddhist psychology and the teachings of the Dalai Lama. Using such new techniques as PET scans and functional MRIs, which make it possible to visualize living brains, they have been able to show that individuals trained in meditation have different brain activity from those without such training, and they respond differently to situations that would cause most of us to lose our emotional equilibrium. The broader implication of this research is that changes in the mind can cause changes in both the function and structure of the brain, a fact that cannot be explained by the biomedical model and that suggests many more options for taking charge of our emotional well-being.

In retrospect, seeing human beings as nothing more than the sum of biochemical interactions was probably a necessary stage of medical evolution. Medical systems of the past lacked the technology to study the biological underpinnings of human health with rigor and precision. Now we have that technology, and we've used it well to gain invaluable insights about our physical bodies. But it is impossible to restore or promote human health unless we begin with a complete definition of a human being. An incomplete definition will always result in incomplete diagnoses and less-than-optimal treatments.

So now is the time to ascend the mountain and see the biomedical model as one part of our broadening view. Our health or lack of it is the result of biochemical interactions and genetics, dietary choices, exercise patterns, sleep habits, hopes, fears, families, friends, jobs, hobbies, cultures, ecosystems, and more. Chemical imbalances in the brain may well correlate with depression, anxiety, and other emotional states but the arrows of cause and effect can point in both directions. Optimizing emotional wellness, by improving attention, changing destructive patterns of thinking, and finding contentment within, can also optimize brain chemistry, correcting any deficiencies in neurotransmitters.

George Engel showed us the path upward more than thirty years ago. Now, I am happy to say, we are starting to follow it.

About the author

Andrew Weil, M.D., is a world-renowned leader and pioneer in the field of integrative medicine, a healing oriented approach to health care which encompasses body, mind, and spirit.