Yet we'd feel that we hadn't done our jobs if we failed to report on a drug that transforms approximately 10 to 20 percent of its users, alleviates depression in another 50 to 60 percent, and has no effect, either positive or negative, on the final 25% or so. (These figures, incidentally, are not confined to depression, but have been demonstrated in patients treated for obsessive-compulsive and eating disorders as well.)
Jerrold Rosenbaum, M.D., of the Clinical Psychopharmacology Unit at Massachusetts General Hospital, sums up both the caution and the excitement: "People who don't need this medication shouldn't take it. Yet it has allowed me to treat beyond the boundaries of where I used to treat before." - Ed.
My first experience with Prozac involved a woman named Tess, the eldest of 10 children born to a passive mother and an alcoholic father, who was physically and sexually abused as a child. When Tess was 12, her father died and her mother entered a clinical depression from which she had never recovered. Tess-one of those inexplicably resilient children who flourish without any apparent source of sustenance-took over the family.
In time, Tess made a business career out of her skills at driving, inspiring, and nurturing others. Still, her personal life was unhappy. Tess stumbled from one prolonged affair with an abusive married man to another. As these degrading relationships ended, she would suffer severe demoralization. The current episode had lasted months, and, despite psychotherapy, she was progressively less energetic and more unhappy.
When I first met Tess, I ran down the list of signs and symptoms of clinical depression, and she had them all: tears and sadness, absence of hope, inability to experience pleasure, loss of sleep and appetite, guilty ruminations, poor memory and concentration. But for her many obligations, she would have preferred to end her life.
Had I been working with Tess in psychotherapy, we might have begun to explore hypotheses regarding the source of her social failure. (For the past four years her principal social contact had been with a married man named Jim who came and went as he pleased and finally rejected Tess in favor of his wife.) Instead, I was relegated to the surface-to what psychiatrists call the phenomena.
Depression is a relapsing and recurring illness. The key to treatment is thoroughness. If a patient can put together a substantial period of doing perfectly well-five or six months, some experts say-the odds are good for sustained remission. But to limp along just somewhat improved is dangerous. The partly recovered patient will likely relapse as soon as you stop the therapy, or as soon as you taper the drug. And the longer someone remains depressed, the more likely it is that depression will continue or return.
When Prozac was released by the FDA, I prescribed it for Tess for entirely conventional reasons-to terminate her depression and to return her to her "premorbid self." My goal was not to transform Tess but to restore her.
But medications do not always behave as we expect them to. Two weeks after starting Prozac, Tess reported that she was no longer feeling weary. In retrospect, she said, she had been depleted of energy for as long as she could remember, and had almost never known what it was like to feel rested and hopeful. She had, it now seemed to her, been depressed her whole life, and she was astonished at the sensation of being free of depression.
With this new demeanor came a new social life. Within weeks of starting Prozac, Tess settled into a satisfying dating routine. I'd never seen a patient's social life reshaped so rapidly and dramatically. Low self-worth and poor interpersonal skills-the usual causes of social awkwardness-are so deeply ingrained and difficult to influence that ordinarily change comes gradually, if ever. But Tess blossomed all at once.
"People on the sidewalk ask me for directions! " she said. They never had before.
The change went further. "I never think about Jim," she said. And in the consulting room, his name no longer had the power to elicit tears.
This last change struck me as most remarkable of all. When a patient displays any sign of social masochism-as Tess did in her acceptance of Jim's behavior-psychiatrists anticipate a protracted psychotherapy. It is rarely easy to help a socially self-destructive patient abandon humiliating relationships and take on ones that accord with a healthy sense of self-worth. But once Tess felt better, the masochism just withered away and she seemed to have every social skill she needed. Even her relations to those she watched over changed she was no longer drawn to tragedy, nor did she feel heightened responsibility for the injured.
There is no unhappy ending to this story. Tess did go off medication after about nine months, and she continued to do well. She was, she reported, not quite so sharp of thought, so energetic, so free of care as she had been on the medication, but neither was she driven by guilt and obligation. She was altogether cooler, better controlled, less sensible of the weight of the world than she had been.
Then, after about eight months off medication, Tess told me she was slipping. "I'm not myself," she said. She felt she could use the sense of stability, the invulnerability to insults, that Prozac gave her. Here was a dilemma for me-ought I to provide medication to someone who was not depressed? I assumed I would be medicating Tess's chronic condition; who was I to withhold the bounties of science?
Again, on Prozac, Tess responded as she had hoped she would, with renewed confidence, self-assurance, and social comfort.
I believe Tess's story contains an unchronicled reason for Prozac's enormous popularity: its ability to alter personality. Here was a patient whose usual method of functioning had changed dramatically. She became socially capable, vivacious and fun-loving. Before, she had pined after men; now she dated them without need to romanticize or indulge their shortcomings.
Not all patients on Prozac respond this way. Some are unaffected, some merely recover from depression, as they might on any medication. But a few are transformed. Prozac gives these patients the courage to do what needs to be done. Moreover, Prozac has few side effects. Patients do not feel drugged or medicated.
TRUE OR FALSE SELF?
No doubt doctors should be pleased when their patients get better quickly, but I confess I was unsettled by Tess's enthusiasm. I was suspicious of Prozac, as if I had just taken on a cotherapist whose style left me wondering whether she was wholly trustworthy.
But Tess never showed signs of mania: She did not manifest rapid speech or thought, her judgment remained sound, and, though she enjoyed life more than she had before, she was never euphoric or Pollyannaish. She was "normal," in mood and level of energy alike, but her place on the normal spectrum had changed.
Perhaps my discomfort with Tess's makeover had another component. It is all very well for drugs to do small things: to induce sleep, allay anxiety, ameliorate a well-recognized syndrome. But for a drug's effect to be so global-to extend to social popularity, business acumen, self-image, energy, flexibility, sexual display-touches too closely on extreme fantasies about medication for the mind.
Medication usually does not transform-it heals. When faced with a medication that does transform, even in this friendly way, I became aware of my own irrational discomfort, a sense that for a drug to have such a pronounced effect is inherently unnatural, unsafe, even uncanny.
I might have come to terms with this discomfort, but Tess's sense of dislocation did not disappear immediately, and her surprise at her altered self helped me to understand the more profound sources of my own concern. The changes in Tess, ones I saw replicated in certain other patients given Prozac, raised unsettling issues.
How, for example, would Prozac affect the doctor's role? To ameliorate depression is all very well, but it was less clear how psychiatrists were to use a medication that could lend social ease, command, even brilliance. And how would society be affected by our access to drugs that can alter personality in desirable ways?
For years, psychoanalysts were criticized for treating the "worried well," or for enhancing growth rather than treating illness. Who is not neurotic? Who is not a fit candidate for psychotherapy? But I wondered whether we were ready for "cosmetic psychopharmacology." Is it legitimate for a doctor, in the absence of depression, to treat a patient like Tess? Now that questions of personality and social stance have entered the arena of medication, we as a society will have to decide how comfortable we are with using chemicals to modify personality in useful, attractive ways.
But my central concern involved her personhood: Are we willing to allow medications to tell us how we are constituted? An indication of the power of medication to reshape a person's identity is contained in the sentence Tess used when she telephoned me to ask if she might resume her Prozac. She said, "I am not myself."
I found this statement remarkable. After all, Tess had existed in one mental state for 20 or 30 years; then she briefly felt different. Now that the old mental state was threatening to re-emerge, she felt that she was not herself. But who had she been all those years if not herself? Had medication somehow removed a false self and replaced it with a true one? Might Tess have lived her whole life and never been herself? Just how far are we - doctors, patients, society at large-likely to go in the direction of permitting drug responses to shape our understanding of the authentic self.
By the time Tess's story had played itself out, I had seen perhaps a dozen people respond with comparable success to Prozac. Hers was not an isolated case, and the issues it raised would not go away. Charisma, courage, character, social competency-Prozac seemed to say that these and other concepts would need to be re-examined, that our sense of what is constant in the self and what is mutable, what is necessary and what contingent, would need to be revised.
UP vs. DOWN
The debate about Prozac was catalyzed by a young Harvard psychiatrist, Robert Aranow, M.D., who challenged his colleagues to consider the ethical implications of "mood brighteners," a phrase he coined after seeing Prozac exert a dramatic effect on certain of his less ill patients. Aranow defined mood brightener as a medicine that can "brighten the episodically down moods of those who are not clinically depressed, without causing euphoria or the side effects that have accompanied the mood elevators of abuse," such as cocaine or amphetamine. Aranow stressed the lack of side effects in order to sharpen the discussion: Once we set aside the argument that drugs are bad because they harm people physically, we are forced to focus on whether we want to be able to use drugs to improve normal people's moods.
Prozac made Aranow wonder about the ethical implications of a drug that demands no tradeoff. He further highlighted this issue by formulating the concept "conservation of mood." Amphetamine, cocaine, heroin, alcohol, and other street drugs used to elevate mood all ultimately result in a "crash." What interested Aranow were the consequences of mood-elevating drugs that violate the principle of conservation of mood-that break the rule of "what goes up must come down."
Aranow's inspiration was a case involving a 44-year-old woman who two days a week tended to feel apathetic and unable to complete her usual tasks. She met criteria for none of the depressive disorders, though she did appear to have a "personality disorder" characterized by dependency and passive aggression. The patient apparently struck her doctors as being a whining complainer.
At the patient's insistence, Prozac was prescribed. Six weeks later, she reported more energy, optimism, and confidence: "This is the way I've always wanted to feel." Twice she was weaned off Prozac, and each time she returned to her normal, unsatisfactory level of functioning. Back on the medication, her energy and optimism returned. She never became manic and never suffered a collapse in mood.
This case led Aranow to challenge his colleagues to think about the implications of a harmless drug that could "reduce the common experiences of drudgery, such as going to work Monday mornings, for those who are not seen as suffering from a mood disorder."
In a similar vein, we all react to disappointments, even minor ones. A date stands us up. A colleague makes a cutting remark. The business proposal, the grant submission, the application for promotion is rejected. Always there is a visceral response: the sinking in the stomach, a feeling of weakness, confusion of thought, a momentary sense of sadness and worldweariness. It will pass, we know, but for the moment we are deeply affected.
Yet for some this pain is worse than others-it lasts longer, paralyzes more thoroughly. They are not depressed, but they are vulnerable. "Sensitive" is what we call such people. It is not only what a person feels but also how he or she shows it that makes for sensitivity. Someone who displays a slight wound too insistently, or who too assiduously avoids the risk of disappointment, is labeled oversensitive.
What lies behind oversensitivity? One idea is that certain people are physiologically wired to be deeply sensitive to rejection. After experiencing a loss, these people feel more pain or come closer to depression than do most men and women. According to this theory, a variety of personality styles, typical behaviors, and even mental illnesses can be traced to the complex adaptations oversensitive people make to the abnormality in their emotional thermostat.
Lucy, another patient of mine, was a college student with a damaged self-image, a tendency to place men first, and a willingness to put herself at risk. Her history is dominated by one event. When Lucy was 10 and living in a third-world country where her father was stationed, she came home to find her mother brutally murdered. Lucy showed no immediate reaction to this ghastly occurrence. She remained a productive, well-liked girl, although her father's attention to his work hurt her repeatedly. She often felt he was not there when she needed him. To the part of her that every moment remembers her mother's murder, the world is so fraught with danger that to exercise caution seems derisory self-delusion.
Lucy understands her sensitivity originates in the apprehension that she will lose anyone she loves. But she cannot shake it-it has a life of its own. The smallest slight throws her into a tailspin. Although she may start the day optimistic and focused, she knows she may at any moment be swamped by despondency.
During a period of particularly disorganizing upset, I started Lucy on Prozac. Her initial response was promising. The medication interrupted her downward spiral. She reported a newfound ability to "back off " in her relationship with her boyfriend. The medication may have allowed her to stay at school and to preserve the romance. These effects were of some importance; they stabilized her life.
It was not possible to keep Lucy on Prozac. She reported an increase in her sense of undirected urgency. She had to do something, yet she did not know what. Case reports had emerged of Prozac's causing patients to experience suicidal ruminations, and I thought that Lucy's agitation resembled aspects of incidents in those reports. I might have tried another antidepressant, but without any medication Lucy began to feel better.
The brief period on medicine allowed Lucy to understand her social behavior as stemming from exaggerated apprehensiveness. We might say the medication acted like an interpretation in psychotherapy; it gave Lucy a new perspective. Or perhaps a biological effect of Prozac-the calming of an overexcited system-had something to do with Lucy's ability to change.
Even if medication fails, the patient and the therapist alike may tend to think that the biological problem persists, untreated. In Lucy's case, I turned to a second medication. Lucy began taking Zoloft, a new antidepressant that, like Prozac, inhibits serotonin reuptake without directly affecting other neurotransmitter systems. After four weeks she reported a striking change. She began to prefer space and time to work alone.
I don't imagine Lucy would have done as well without psychotherapy. And yet she harbored a kernel of vulnerability that the psychotherapy did not touch. It was as if psychological trauma-her mother's death, the years of struggle afterward-had produced physiological consequences for which the most direct remedy was a physiological intervention.
THE FREEDOM TO FEEL
Richard Schwartz, a coworker of Robert Aranow, suggests that mood brighteners interfere with a person's relationship to reality in a way that traditional antidepressants do not. If depression entails a distortion of perception-the sufferer sees life as more bleak than it is-then antidepressants make a depressed person once again responsive to reality. Recovery from a depressive illness therefore involves an act of connection, of integration.
But nonpatients those who are in ordinary pain-are merely in touch with reality and their own human vulnerability. To use a pill to improve their mood is, Schwartz asserts, an act of disconnection. You bring about a break, however small, between the individual and either his external reality or his humanity-his tendency to react "humanly" to circumstance. Furthermore, he goes on to argue that mood brighteners interfere with a person's necessary struggle to attain "affect tolerance"-the ability to withstand feeling what it is you're feeling.
Randolph Neese, a University of Michigan psychiatrist, criticized mood brighteners because, he argued, bad feelings are useful. Pain, diarrhea, and nausea are distressing, but all carry information vital to survival. Unpleasant mood states are similarly adaptive. Anxiety protects us from heedlessly attacking powerful leaders; the internal threat of depression moderates our primitive urges and keeps us comfortable in our sense of stability.
This argument might apply to a shortacting pill that gives someone an hour or two of happiness in the face of loss or humiliation. Given access to such a medicine, someone who is afraid of life might take it intermittently to avert sad moods, while failing to act in the world or face her own fears and weaknesses. But Prozac does something quite different: It lends certain people courage and allows them to choose life's ordinarily risky undertakings.
The fear is that Prozac will rob life of the edifying potential for tragedy; but when Prozac works well, it catalyzes the precondition for tragedy-namely participation. In some patients, Prozac quite directly increases the ability to bear troubling emotions and lets feelings emerge in new settings. Certainly people who become less obsessional on the drug are thereby made more open to emotion. Not only does Prozac increase resilience, in some people it increases the profundity of emotion available to them.
Cure by pill is seen as dehumanizing when compared with psychotherapy even the parts of psychotherapy that relate support rather than insight. The problem is not that the medicine fails to confer affect tolerance or fails to move people toward an adaptive interaction with reality, but rather that it succeeds. In doing just what psychotherapy aims to do, Prozac performs chemically what has heretofore been an intimate interpersonal function.
Prozac is different from mood-altering drugs like marijuana and LSD-which encourage self-absorption-in the sense that it induces pleasure in part by freeing people to enjoy activities that are social and productive. It opens people to pleasures in experience identical to those enjoyed by other "normal" people in their ordinary social pursuits.
RELIEF VS. CREATIVITY
The issue remains whether our discomfort with Prozac is based on reason or whether it is so much pharmacological Calvinism-the belief that pain is a privileged state-the viewpoint that is inherent in the arguments concerning affect tolerance and the adaptive value of sadness. It is also at the heart of Southern writer Walker Percy's novel, The Thanatos Syndrome.
In the novel, a maverick doctor finds that plotters have introduced an insidious chemical, heavy sodium, into the water supply. While on the drug, shy and anxious women become erotic, bold, competitive, and unself-conscious. They shake off "old terrors, worries [and] rages ... like last year's snakeskin."
Percy was a man to whom ailments proved precious. His father committed suicide when Walker was 13; his mother died two years later. After contracting tuberculosis as a medical intern, he called the disease "the best thing that ever happened to me." Percy spent two years recuperating, reading literature and philosophy.
For Percy, as for many of his protagonists, illness and solitude were transforming. In his examination of the pathology of contemporary society, he found a central flaw to be precisely a lack of respect for symptoms such as fear, pain, depression, and anxiety. One might well wonder whether, had he been given Prozac, Percy the seeker would have ever emerged.
One perspective on this issue involves the relationship between suffering (or neurosis) and art. Yet there are many founts of creativity, and not all artists suffer. There is also the issue of whether an artist who does suffer denies the muse if he or she chooses relief from pain. Is it true that to relieve suffering is to stifle art? Psychiatrists have claimed manic depression is correlated with creativity, but there is no evidence that psychotherapy destroys creativity in its treatment.
My sense is that antidepressants improve creativity in certain people. According to both psychoanalysis and Percy's view, to lose pain without quest or struggle-perhaps to lose pain at all-is to lose self. For Percy, the problem is not that the artist loses his art when he takes a Pill, but that he loses his art because of the greater loss of what is distinctly human.
Yet, in my experience, many patients including some who may never have had a diagnosable mental illness-are better able to explore both their past and their current circumstances while they are taking Prozac. For these people, to whom medication constitutes help in recovery from childhood trauma or protection from the threat of terrible decompensation, the drug seems to aid rather than inhibit the struggle to locate the self.
My own belief is that that moral sensibility can arise in the company of a variety of affect states. The drive that results from inborn compulsiveness and pain experienced in childhood is only one reason to search for transcendence, and if to lessen that drive ruins us morally, then our moral predicament is sad indeed. Still, we cannot escape entirely the fear that a drug that makes people optimistic and confident will rob them of the morally beneficial effects of melancholy and angst.
HUMANISM VS. SCIENCE
In the psychopharmacologic era, when we look at our children, we will attend more to their constitution and less to the influence we have brought to bear. At the same time, we will worry about losses our children suffer, about our failures in empathy towards them, about the pains that can elevate stress hormones and stimulate dysfunctional neuronal sprouting.
The personality-altering pill is high technology, something unknowable, foreign, perhaps even hostile. Psychoanalysis was criticized for creating a cult of expertise, but analysis was at least a joint effort, a journey of self-exploration for the patient, with feeling, insight, and intuition as guides. In this context, pharmacology may seem self-alienating when, in particular instances, it restores people to themselves. In this regard, we may recognize in ourselves a certain prejudice in favor of humanism and against science.
None of the ethical concerns about Prozac have disappeared. But once we have lived with Prozac awhile, these worries may seem less urgent. Our worst fear was that the medication would rob us of what was uniquely human: anxiety, guilt, shame, grief, self-consciousness. Instead, medication may convince us that those affects are not uniquely human, although how we use or respond to them surely is.
In the end, I suspect the moral implications of Prozac are difficult to specify, not only because the drug is new, but because we are new as well. Like so many of the "good responders" to Prozac, we are two persons, with two senses of self. What is threatening to the old self is already comfortable, perhaps eagerly sought after, by the new. Here, I think, is Prozac's most profound moral consequence, in changing the sort of evidence we attend to, in changing our sense of constraints on human behavior, in changing the self.
Is Prozac a good thing? Asking the virtue of Prozac may seem like asking whether Freud's discovery of the unconscious was a good thing. Once we are aware of the unconscious, once we have witnessed the effects of Prozac, it is impossible to imagine the modern world without them. Like psychoanalysis, Prozac exerts its influence not only in its interaction with individual patients, but through its effect on contemporary thought. In time, I suspect we will come to discover that modern psychopharmacology has become, like Freud in his day, a whole climate of opinion under which we conduct our different lives.
Excerpted and abridged from Listening to Prozac-A Psychiatrist Explores Mood-Altering Drugs and the Meaning of the Self (Viking; 1993) by Peter Kramer, M.D. Copyright 1993 by Peter Kramer; used by permission.
SEROTONIN AND PROZAC
Serotonin is one of several neurotransmitters-chemicals that nerve cells in the brain use in communicating with one another. Unlike other neurotransmitters, its receptors are not localized in a few specific areas of the brain; hence, its uptake and release affects much of our mental life, including depression.
Yet serotonin's effects on mood and behavior extend beyond its role in acute illness. Monkey research, for example, shows, that high serotonin levels correlate with dominance in the troop. Preliminary human studies show serotonin to relate to drive and status in ambitious young men. In addition, low serotonin levels have been implicated in a variety of functions, from anxiety to impulsivity. Some researchers speculate that serotonin relates to an overall sense of security.
Neurotransmitters such as serotonin are active when they sit in the gap, or synapse, between nerve cells. Transmission is ended by a process in which the chemicals are taken back up into the transmitting cell. Drugs such as Prozac are called "selective serotonin reuptake inhibitors," or SSRIs; they work by slowing the reuptake of serotonin, thus making it more available to the receiving cell and prolonging its effect on the brain.
THE BIG THREE
One of the big advantages of selective serotonin reuptake inhibitors, or SSRIs, over older antidepressants is that they produce far fewer side effects. Still-to differing degrees depending on the drug and dosage-all SSRIs do produce nervousness, anxiety, dry mouth, constipation, and blurred vision, among other effects. For most patients, however, these symptoms seem to disappear over time.
Two other popular SSRIs marketed in the United State are Zoloft and Paxil. While these drugs differ somewhat from one another in chemical structure, they are all potent. Yet each seems to have a "personality" all its own: one drug may work better than the others for a certain patient, though doctors are still unsure exactly why. Such patient-specific efficacy, as well as possible side effects, helps physicians establish guidelines for prescribing. Someone feeling "on edge" might take Zoloft over Prozac, for example; while an insomniac might prefer Paxil and a patient known to forget his medication might be better off with Prozac.
Prozac (fluoxetine) has been on the market the longest, having been approved by the FDA in December 1987, and doctors are quite familiar with it. The drug has a long half-life (time it remains in the body), which cuts down on withdrawal symtom when medication is stopped, allowing the body to be weaned off slowly-usually over a period of six to eight weeks. That's also a plus for patients who for some reason skip a dose-they are less likely to feel major effects than they would with a drug with a shorter lifespan.
Zoloft (sertraline) was approved by the FDA in December 1991. Some physicians prefer it to Prozac because it leaves patients feeling less jittery. In addition, its shorter half-life-two weeks to wash out of the bodyallows for a quicker change in prescription. The downside, of course, is that a missed dose could bring a return of symptoms.
Paxil (paroxetine) was introduced in 1993. It also has a shorter half-life and leaves patients feeling less jittery than Prozac. Though it may interfere with sleep less than the other two, it reportedly produces a feeling of being "wiped out." Because of its newness, doctors do not have a lot of clinical experience with Paxil. Although the drug has the most potent effect on serotonin reuptake of the three, it may nevertheless be no more effective than the others in practice.