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But even Prozac cannot turn a unipolar depressive into a cheerleader or a talk show host—unless the manic predisposition is already there. When it is, in however latent a form, transformations such as those described in Peter Kramer’s provocative book Listening to Prozac can and do take place. Prozac in that case does seem to have the ability to turn whining nitpickers into optimists, to allow longtime depressives to wake up looking forward to the day, and to give previously depressed people the wherewithal to make important changes in their lives. A limited number of psychiatrists have reported seeing major metamorphoses in these patients—more so than with other antidepressants, even though those medications also produced striking changes.

Still, the issue is a fuzzy one, because die evidence is based more on patient perception and physician perspicacity than on anything measurable with standard diagnostic tools. This question has yet to be studied in a scientific way. Up to 10% of patients who undergo transformation with Prozac already had a mild tendency to experience elevated moods. With Prozac, they were finally able to achieve consistently this high level of functioning.

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There’s no question that psychotropic drugs of all kinds, including anti-anxiety drugs, mood stabilizers, tranquilizers, and antidepressants, have the power to transform. When you change an individual’s mood, lifting a person out of a depression (or calming down someone who is experiencing a manic high), that person’s emotions, behavior, and even motor activity alter right along with (he mood. A person who is less depressed becomes by definition livelier, more hopeful, and more energetic. It might sound like a transformation, but most patients don’t experience it that way. This is an important change, no question about it. But to label it a transformation is, in my view, to romanticize it and ignores the widely known genetic studies in this field. The reality is that all depressives, once they have returned to their normal state of mind, will say that they feel better about themselves and are more outgoing, efficient, and assertive. All antidepressant drugs can achieve those results. This is not news. Similarly, when depressed people with the propensity toward manic and hypomanic periods take antidepressant drugs, they tend to feel a greater sense of well-being than those without that propensity. And, because they are often dramatic, rejection-sensitive, histrionic personalities who magnify the elements of their lives, they make persuasive claims. They don’t just feel better, they will tell you that with Prozac, they feel better than they’ve ever felt in their lives.

This is not news either, although the media has made it seem so. To thousands of experienced psychopharmacologists around the world, this has been articulated for at least thirty years in scientific journals and at conferences. As a group, these patients are hyperresponders who respond to all antidepressants and stimulants. And sooner or later, with every antidepressant that we’ve had, some of them slip into manic psychosis and end up in the hospital.

A few cases nonetheless appear to offer a stronger case for transformation, partially because these patients will waltz into the office on the very next visit and announce that they have been transformed. And indeed, the change is often dramatic. These patients are not merely lifted out of depression; they are elated. In the overwhelming number of cases, the reason for this so-called transformation is that these patients—often rapid responders—have always had a dual nature; they are sometimes depressed—sometimes for years on end—and they are sometimes, perhaps not as frequently, revved up. They are, in short, subtly bipolar. These are not full-blown manic-depressives; but they do have a family history of or a mild tendency toward the elevated moods of hyperthymia, hypomania, or cyclothymia. Prozac—or any other antidepressant, often enough—will nudge them into the manic zone—a place they have been before. Once there, they feel very, very good. And they will tell you so in vivid, dramatic language. But is this a

transformation? If you think of the patient as a depressive, it may appear to be. If you think of the patient as a soft bipolar, it is not.

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Depression, especially as laypersons use the term is a bleak mood typically characterized by discouragement, sadness, or despair. In a sense, anxiety, with its finger-drumming restlessness, and depression, with its hopeless inertia, are quite different, which is why psychiatrists classify anxiety disorders Separately from depressive disorders. Yet the two feeling states so frequently overlap and co-exist that the difference between anxiety and depressive disorders is confusing. The primary diagnosis is based on the answer to a simple question: in the life history of the patient, which state did the patient experience first?

Thus, in anxiety disorders, anxiety is the primary symptom and often the first symptom, even though frequently secondary depression is present. Anxiety disorders include:

• general anxiety disorder

• phobic disorder

• panic disorder

• obsessive-compulsive disorder

• post-traumatic stress disorder (PTSD).

In depressive disorders, the depressed mood usually appears first as the primary symptom and is normally the most important part of the illness. However, although anxiety is not always present in depressive disorders, most of the time it lurks beneath the surface in varying degrees and may be present as one of a number of symptoms within the depressive syndrome.

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Different mechanisms of action produce different side effects. The blockage of norepinephrine uptake, for instance, can produce tachycardia, tremor, and sexual dysfunction. Blocking dopamine (a process important to the antidepressants Asendin and Wellbutrin) can produce movement disorders and changes in the endocrine system. Blocking serotonin avoids those problems for the most part but can create instead gastric distress, insomnia, and anxiety.

In addition, many antidepressants work on the other side of the synaptic gap, blocking the receptors that normally pick up the neurotransmitters. Again, the side effects depend on which receptors (among them Alpha1, Dopamine D7, Histamine H1 and muscarinic receptors) are being blocked. Block the Histamine H1 receptors and you’re likely to see sedation and weight gain. Block the muscarinic receptors, and you can expect blurred vision, a dry mouth, constipation, and an impaired memory.

The more an antidepressant participates in these processes, the more side effects it is likely to produce. Thus, a tricyclic antidepressant such as armtriptyline (Elavil), which blocks the uptake of norepinephrine and serotonin as well as all four receptors listed above, is also associated with a much higher incidence of side effects than is Prozac, which is more limited, and thus more specific in its action.

Unlike older medications, Prozac blocks receptors only minimally, making it the first but not the only antidepressant for which this is true. Other SSRIs and Effexor also interfere very weakly with the receptors.

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However, patients who discontinue the drug will most often rebound into the previous depressive condition. Chronic diseases such as depression, obsessive-compulsive disorder, and bulimia are likely to return because most of these conditions are psychobiological. Once the treatment is removed, the biological component of the illness will revert to its original state, and the illness usually returns.

If the illness is intermittent and the patient goes off Prozac, the depression may not come back immediately, but it is very likely to return at some point in the future. After an initial episode of depression, the chances of experiencing a second episode are probably better than 50%. (A study in Europe found that the likelihood was much higher—between 70% and 80%.) Even more impressively, a second episode is followed by a third episode in 80% to 90% of the cases.

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