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Scott Mendelson, M.D. Headshot

Psychiatry's Dirty Little Secret

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When I was in medical school, I learned one of psychiatry's dirty little secrets. That is, that of people prescribed an antidepressant to treat their Major Depression, only about 25% enjoy complete resolution of symptoms, another 50% feel some but not complete relief, and the last unfortunate 25% get no relief at all. This was true 15 years ago and remains true today. As a psychiatrist, I prescribe antidepressants, and I have seen these medications improve and even save lives. There is substantial evidence in the scientific literature that certain individuals are genetically predisposed not only to develop Major Depression, but also to respond to certain types of antidepressants. Thus, there is firm basis to believe that certain individuals have specific deficits in their brain chemistries that can cause Major Depression either "out of the blue" or, more commonly, when stressful situations grow and persist beyond one's capacity to deal with them. It is likely that such people are among those that benefit from antidepressant treatments. But what of those that do not respond to antidepressants? I am happy to say that there is a growing recognition among psychiatrists that mere reduction in symptoms must not be the goal of treatment. Rather, remission of symptoms is what our patients deserve, and this should be what we strive to provide all of our patients.

One approach to bringing full remission of symptoms to patients resistant to antidepressants is augmentation of the antidepressant medication. That is, the addition of another psychoactive medication, with a different mechanism of action, to enhance the effect of the antidepressant and resolve symptoms. Studies have shown that such action can help resolve symptoms in a significant number of patients whose symptoms have resisted the effects of single medication. In fact, I was somewhat startled to see a new commercial on television pitching the use of a drug to add if depression persists while taking an antidepressant. Unfortunately, the costs, side effects, and risks of dangerous drug interactions increase with the addition of a second or even third medication. More importantly, we lack information on the physiological basis and necessity for adding medications.

Prudent psychiatrists look beyond psychoactive medications when a patient presents with Major Depression. Often, despondency is the natural response to adversities of life, and counseling, either alone or in combination with an antidepressant, is the best approach to treating a case of depression. It is also often the case that antidepressants are in order, but inadequacies such as low thyroid hormone, vitamin deficiencies, or substance abuse need to be remedied before the medication can provide all of its benefits.

All psychiatrists in training are exposed to the so-called Bio-Psycho-Social model of mental illness, which states that mental health or illness is the product of complex interactions between the brain, ways of seeing the world, and the way people interact with one another. Unfortunately, there has been a tendency to give short shrift to the role that diet plays in the prevention and treatment of Major depression. A new study in the British Journal of Psychiatry has found that people who eat a diet rich in whole grains, fresh fruit, vegetables and fish, have a 26% less chance of developing Major depression than do those who eat diets loaded with fried food, processed meat, refined grains, sugary desserts and high-fat dairy products. Although the latter diet is likely to be deficient in certain vitamins and minerals, the most concerning effect of a diet loaded with sugar and saturated fat is the development of Metabolic Syndrome.

Metabolic Syndrome is defined by the presence of high levels of fat in the form of triglycerides in the blood; low blood levels of the good cholesterol, HDL; high fasting blood sugar; high blood pressure; and abdominal obesity, which many people refer to as a pot-belly or spare tire. Although Metabolic Syndrome is well known to predispose to heart disease and diabetes, the fact that it also predisposes to Major Depression has been underappreciated. Among the ways that Metabolic Syndrome likely increases the risk of depression is by decreasing the sensitivity of insulin in brain tissue; stimulating liver functions that rob the brain of substrate for important neurotransmitters; increasing levels of the stress hormone, cortisol; and increasing blood levels of potentially detrimental substances called adipocytokines that are released in too high a concentration from abdominal fat cells stretched beyond their capacity to maintain normal function.

The reliance on "comfort foods", substance abuse, unwillingness to exercise, poor sleep, and stress seen in Major Depression is suspected of increasing the risk of metabolic Syndrome. However, there is considerable evidence that having Metabolic Syndrome may significantly increase the risk of developing Major Depression. Insulin resistance, thought to be the underlying basis of Metabolic Syndrome, is four times more likely to be seen in people with Major Depression than in those without this condition. The diagnosis of Major Depression in individuals with Diabetes is roughly three times that seen in the general population. Obesity, particularly the abdominal obesity of metabolic syndrome, is also known to increase the risk of Major Depression.

Although the pathophysiology of Metabolic Syndrome is enormously complicated, the means to treat or prevent the syndrome is astonishingly simple. To minimize the risk of Metabolic Syndrome, we must encourage diets low in sugars and saturated fats, exercise, weight control, stress reduction and adequate sleep. Some individuals are genetically predisposed to Major Depression. However, by reducing the incidence of Metabolic Syndrome, the risk of depression will be substantially reduced and the cases of depression that do arise may be more easily treated. The reliance on expensive and potentially dangerous combinations of psychoactive medications to bring relief to patients with treatment-resistant Major Depression may thus be avoided.

Dr. Mendelson is the author of the new book, Beyond Alzheimer's (

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