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Prozac, depression, serotonin and Tourette Syndrome.

Prozac, or fluoxetine, has rapidly become one of the most widely prescribed medications in the United States. Articles have appeared extolling its virtues in Newsweek, New York magazine and many segments of the popular press. However, recently considerable concern has been raised because some individuals taking Prozac have developed obsessional thoughts about committing suicide. Why has Prozac become so popular? What does it do? Is it dangerous?

Chronic depression is a common, serious problem that often goes undiagnosed. In addition to feeling depressed or blue, affected individuals often sleep excessively, feel tired all the time, have no motivation to do things, are irritable and often difficult to live with, and may have temper outbursts over minor things. Many other disorders can cause these symptoms, but depression is one of the most common. Some people with chronic depression may have been depressed from such an early age that they do not know what it is like to not be.

For decades, major depression was thought to be caused by some form of emotional conflict, often assumed to have had its origins early in life. However, in the 1950s it was discovered that some medications used to treat tubercolosis had the side effect of causing mood elevation.

This soon led to the development of two major types of antidepressant drugs. One was the tricyclics (imipramine-Tofranil; desipramine-Norpramin; amitripline-Elavil; trazodone-Desyrel and others). The second type was the monamine oxidase (MAO) inhibitors (phenelzine-Nardil; isocarboxazid-Marplan; tranycypromine-Parnate and others). These medications had similar effects on the brain -- they increased the efficiency with which the brain used two neurotransmitters -- norepinephrine and serotonin. Knowledge of these drugs led to development of the modern neurochemical theories of depression and other behavioral disorders. Major depression was felt to be caused by the presence of too little norepinephrine or serotonin in the brain, and the medications effectively increased these levels. Because depression often runs in families, genetic factors were believe to play an important role in causing the defective levels of norephinephrine and serotonin.

The problem with the tricyclics was that they often caused side effects such as dry mouth, constipation and tiredness. The problem with the MAO inhibitors was that people taking them had to avoid certain foods, like cheese and wine, to avoid high blood pressure. Thus, while millions of individuals suffered from major depression, only a fraction were taking medications for it either because the depression had gone undiagnosed, or they thought it was a character flaw that they should be able to manage themselves, or the medications used to treat it could have unpleasant side effects.

Over the past decades researchers have been increasingly aware that serotonin is more important in the etiology of depression and a number of other psychiatric problems, than norepinephrine. Thus, if medications could be found which specifically increased the brain's ability to use serotonin, they might both be more effective and have fewer side-effects. The first such medication, primarily affecting brain serotonin and released in the United States, was Prozac. Both turned out to be true -- it was often much more effective in treating depression than the older drugs, and it generally had fewer side-effects. All medications have potential side-effects and the major problems patients experienced with Prozac were insomnia, a queasy stomach and weight gain.

Individuals with depression who had tried both the older medications and Prozac were quick to realize these differences. The word soon spread, first slowly among physicians, then rapidly in the popular press.

One of the things that happens when huge numbers of people take a medication is that a side-effect that is usually rare can start appearing. The report that some individuals taking Prozac developed obsessional thoughts about suicide appears to be such an example. In my experience in prescribing Prozac for hundreds of individuals, I have yet to see this problem, but everyone taking this medication should be apprised of this potential. This is similar, but not identical, to a more common problem with the use of any antidepressant. Sometimes individuals are suicidal but so depressed that they don't have the energy to commit suicide. However, as the antidepressant begins to work, there can be a short period when they are still suicidal but their depression has improved enough that they now have sufficient motivation to carry out their plan. This is a potential danger with any treatment of depression.

As Prozac came into wider use, it was found to be effective in the treatment of a wide range of other behavioral disorders including panic attacks, bulimia, obsessive-compulsive behaviors, compulsive eating and conduct disorder.

My interest in Prozac came out of my involvement with a hereditary behavioral disorder called Tourette Syndrome (TS) (1). The primary diagnostic feature of TS are muscle tics (rapid eyeblinking, facial grimacing and other muscle jerks) and vocal tics (throat clearing, spitting, squeaking, barking and other noises). Compulsive swearing is present in a small percentage of individuals, but is not necessary for the diagnosis. TS was once thought to be extremely rare, but recent studies have shown that milder forms of TS are quite common. A recent study of ours indicated it was present in 1 in 100 schoolboys.

The intriguing aspect of Tourette Syndrome is that affected individuals often have a wide variety of other associated problems including attention deficit hyperactivity disorder (ADHD, hyperactivity), obsessive-compulsive behaviors, mood swings, depression, premenstrual syndrome, conduct disorders, self-abusive behaviors, sleep disorders (insomnia, racing thoughts, night terrors, sleepwalking), addictive behaviors (alcoholism, drug abuse and compulsive eating), panic attacks, anxiety, phobias, learning disorders and dyslexia.

Most of the associated behaviors in Tourette Syndrome have at one time or the other been suspected of being caused by abnormalities in brain serotonin. Thus, when our TS patients, or their relatives, had some of these additional problems we often treated them with Prozac. In approximately 60% some or all the symptoms were eliminated. In some cases, the Prozac was effective for several weeks or months and then became less effective. In others, the improvement persisted.

As we have proposed that the genes causing TS primarily affects serotonin metabolism, it came as no surprise that Prozac was being shown to be effective in a wide range of disorders, and that these are the same problems that are common in TS patients and their relatives.

While generally thought to be caused by a single abnormal gene (i.e. dominant inheritance) recent studies of ours have suggested that most individuals with TS have actually received a gene from each parent and that fairly severe TS is predominantly recessive. However, we do think that individuals carrying a single gene can have tics or a range of some of the above behaviors. If these hypotheses are correct then up to 15% of the general population may carry the TS gene and about half may have one or more of the above symptoms.

This common gene could account for the popularity and the effectiveness of Prozac.

(1) Comings, D.E.; Tourette Syndrome and Human Behavior
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Title Annotation:includes bibliography and article on nutrition and compulsive disorders
Author:Comings, David E.
Publication:Nutrition Health Review
Article Type:Evaluation
Date:Jan 1, 1991
Previous Article:Tourette Syndrome and Human Behavior.
Next Article:Panic disorder. Is it a matter of a defective gene?

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