Listening to Prozac … And Hearing More

THE OPEN MIND
Guest: Dr. Peter D. Kramer
Title: “Listening to Prozac…and Hearing More”
VTR: 9/10/97

I’m Richard Heffner, your host on The Open Mind. And when, in 1993, the brilliant, young psychiatrist Peter Kramer wrote Listening to Prozac, his still unmatched landmark book about antidepressant drugs and what he characterized as the “remaking of the self,” Dr. Kramer joined me here for two of the most stunning possible Open Minds about what we call “the medicalization of personality.”

Clinical Professor of Psychiatry at Brown University, and a private practitioner in Providence, Dr. Kramer has now written a quite compelling afterward to his seminal study of Prozac for a new Penguin soft cover edition. And to begin our program today, I would ask my guest just what he hears that may be somewhat different as he listens to Prozac again. Dr. Kramer?

KRAMER: I think that Listening to Prozac was speculative, even prophetic in a certain way. And when one read it in 1993 there was a sense that it talked about a likely future where we would look at psychology through a biological lens, and where medication would be expected to alter, not just illness, but aspects of temperament. I think very rapidly that has become not the future, but the present. Every day we read in the newspaper about how some or other aspect of personality probably has a genetic basis, has a genetic basis in knockout strains of mice, been shown through knockout strains of mice to have a genetic basis, how there are anatomical effects of depression. And I think the sense is that we are living in a culture where biological explanations for aspects of personality predominate.

HEFFNER: And their treatment?

KRAMER: And the treatment could still, in theory, be psychotherapy or pharmacotherapy, if treatment’s called for. But I think it tends nowadays to start with medication.

HEFFNER: When you were here those years ago, there was, for me, such a nice sense in what you said of a person who didn’t really go with the flow so completely in terms of the medicalization.

KRAMER: Yes. That’s right. I think that this book was a medicine looked at with the eyes of a psychotherapist, saying, “On the one hand, it looks as if medication is doing a lot of what psychotherapy used to do. On the other hand, some of what’s essential about being human, the quest, the search for self, you know, is never going to be done through medication.” And, in addition, this whole scientific array of evidence is less convincing than it’s been made out to be.

HEFFNER: What do you mean?

KRAMER: Well, if you look, for instance, at shyness (that was the best-studied aspect of temperament), there were studies showing that shyness was heritable. If you looked at them carefully, you know, the odds were fairly good that someone who looked at a young age as if he or she was going to turn out to be shy would be very outgoing as an adult. And, on the other hand, some shy adults were recruited from the population of people who looked genetically outgoing. So that really, you know, the odds, the prior probability of predicting that someone is shy were very low. Yes, you know, it looked as if there was some association that was statistically significant, but it wasn’t humanly significant.

HEFFNER: But you were expressing some unease about the use of Prozac, or any drug, in the area that came, in areas that came closer to normal behavior.

KRAMER: Yes.

HEFFNER: Where you weren’t dealing with sick, sick people. And I wonder how you feel about that now.

KRAMER: I’m still disturbed. I think that what has happened is the culture — or the medical profession, certainly — has not taken the option that I laid open in the book, which is to say, “We have to hand, or are likely to have to hand — I would say now we have to hand — some medications that affect normal temperament. And we have to make decisions — societal decisions, I hope, rather than just decisions in a doctor’s office in case after case — about what the proper use is of those biological modalities.”

Instead, what I think psychiatry has done is largely expand the realm of pathology so that now, in addition to major depression, there are many more cases diagnosed of dysthymia, which is chronic, minor depression. And there even is research into what is called “subclinical” or “subsyndromal depressive syndromes.” Well, if it’s subsyndromal, maybe it isn’t an illness; maybe it is a normal variant. And I think that we could have a broader view of what melancholy is. I mean, melancholy is traditionally one of the four ways of being a human being, you know, the choleric, sanguine, saturnine, and melancholic. It’s been recognized all through history. A lot of philosophy… There’s a wonderful book by Martha Nussbaum called Therapy of Desire, a classicist at Brown, that says that a lot of classical philosophy — Aristotelianism, Stoicism, Cynicism, Epicurianism, and so on — is dealing with essentially avoidance of the consequences of melancholy. And if that’s so, then when we meddle with melancholy we’re meddling with one of the normal ways of being a human being. And I think we have to think about what the consequences are rather than just saying, “Well, really we have a more detailed sense of what leads to depression than we used to have.”

HEFFNER: That assumes though a rather fixed notion about the nature of human nature, what it means to be a human being, that one fits into one or another or another or another of those four categories. Can’t we change?

KRAMER: Well, I surely think people do change. Individuals change. I’m not buying the humors theory of the Greeks and the Middle Ages, although I think in some ways it comes in through the back door through serotonin, norepinephrine, dopamine, GABA. There’s a sense that we’re sort of the products of the humors. Yes, people change. Whatever theory we’re under, people change. I think people change biologically, and they change psychologically.

HEFFNER: But I didn’t mean people change; I meant society change in its view it takes of the nature of human nature. What makes up, what constitutes being a human being. If we decide, if our culture moves in a direction, and perhaps we eliminate melancholy. No?

KRAMER: Yes, well, I think that is happening. I think that does happen. You know, I think if, to the extent that we find genetic correlates for melancholy it will look more and more pathological to us. But I want also to invite us to stand back and say, “That isn’t the way human beings have always been seen.” And we could find those genetic underpinnings and say, “Well, they’re differences, but they’re normal variants.” I mean, maybe this is an area where the clichés of the educational system, “differently- abled” and so on really do apply. One can have the artistic temperament and live with it, or one can have the artistic temperament and meddle with it. But it isn’t necessarily treatment of illness so that there’s one protocol for doing it right or wrong.

HEFFNER: Well, of course, in the new edition of Listening to Prozac, in terms of the afterward that you offer, I was quite taken when you wrote here… And let me see. I thought I’d turned down the page, but… Here. You wrote, “If I were writing Listening to Prozac today, I would say that there is suggestive evidence that medication like Prozac can affect normal people, even that it can alter their social behavior, and it may be that these effects are the rule, not the exception.” Do you think they are the rule?

KRAMER: I’m not sure they are the rule. Maybe I’m tweaking the profession a little bit. But when Listening to Prozac came out, one focus was on: Well, does medication change personality at all? And I think one level of that discussion is the discussion we just had, which is that if it affects minor depression it probably is affecting what traditionally has been called “personality.” We may now want to call that “illness.”

But the other question is: Well, what happens to normal people on Prozac? And that question has never been answered by a proper study. But there are some interesting lines of evidence. People have reworked data from studies where Prozac is given adjunctively for smoking cessation and migraine, indications where it doesn’t work terribly well, and they found that people who enter these studies where entry criteria is that you not be depressed, get less depressed anyway on the Prozac. But there’s just been a more interesting study, which has not yet been published, but is out of the University of California by way of people who are now at the National Institutes of Health, where Prozac was given to people with no history or family history of depression. And they were asked to do a negotiating task with another person. And when on… Actually, it was not Prozac. I think it was Paxil, or one of the related drugs that affects the brain in similar ways. When on medication, those people negotiated somewhat better. They were both more collaborative and more able to get their way. And they looked a lot like the monkeys who are dominant monkeys in troops where dominance is very much correlated with the state of serotonin in the brain, which is the factor that Prozac seems primarily to affect. So here, for the first time, at least in a small way, was a study saying, “Yes, this medication affects social functioning of perfectly normal people.” And I think that now the, you know, scientific demand is that those people who think the medicine doesn’t do that have to come up with the evidence.

HEFFNER: And your own personal reaction to that use?

KRAMER: Well, I don’t know that we’re on the verge of using it, you know, unselectively in that way. I think that would be a, I would say, frivolous and somewhat dangerous use of the medication.

HEFFNER: Why?

KRAMER: Well…

HEFFNER: Why frivolous, and why dangerous?

KRAMER: Frivolous because I think there probably are more useful ways to deal with minor alterations of traits like collaboration and assertiveness and so on. I’m not sure that’s a full answer. But dangerous because we really don’t understand what these medicines do, and particularly don’t understand, you know, no research has been done on the effects of these medications on normal people without depression. The whole risk-benefit ratio of medication changes when you’re not really treating anything that demands to be treated.

But I think there’s a practical question that is quite worrisome to me, which is: People are now, for legitimate, serious reasons having to do with recurrence of depression, kept on these medications for very protracted periods of time. And there is no demand by the FDA that the drug companies study the long-term effects of these medications. The FDA rules are really geared toward medicines like antibiotics, where you’re on them for a few weeks, you’re off them for the rest of your life. And it used to be that antidepressants were used that way. Now, because we are so much more aware of the risk of recurrence, and frankly because we’re aware that depression may do things like damage the brain anatomically if it is deep enough or persists long enough, people are kept on antidepressants for long periods of time. And really it is possible that there are side effects that we’re not aware of, because you only discover those side effects through careful comparative studies.

HEFFNER: When we spoke last, when the book first came out, the original version of the book first came out, there was another concern that you had.

KRAMER: Yes.

HEFFNER: And I wonder if we could revisit it. It was a concern as a literary person, as a humanist, as a person who was somewhat uneasy with the monkeying…

KRAMER: Yes.

HEFFNER: …with the…

KRAMER: This was half a concern. Or really it was a concern, and then maybe I undermined the concern after having stated it. Which is that really the human race is enriched by diversity, and that there’s a pressure in this culture for everyone to be bright-eyed, optimistic, assertive, a good salesman, able to make decisions quickly, quick to end relationships, unsentimental, able to do without loyalty. You know, there’s almost a prototype of the successful person in this culture. I mean, there’s an eerie or uneasy congruence between what Prozac does and what the culture demands. And that does make me very uneasy. You know, I think the undermining is saying, “Well, you know, we don’t object too much to psychotherapy altering people’s character traits. If someone is melancholic and sentimental and so on and would like to be more assertive, we would have no trouble if that person went to a psychotherapist and understood what the resistance or reluctance was. So why are we so worried about doing the same job with a medication?”

HEFFNER: Is that because, perhaps, we think that the one is effective and the other isn’t, that the talking cure isn’t all that much of a cure, that the drug is?

KRAMER: Right. I think that would be a cynical answer, and I think it’s partly right, that we’re quite comfortable with a talking cure because it’s not startlingly effective. I think to see people quickly and dramatically change in their style of temperament is very disturbing.

HEFFNER: In Brave New World we reacted to Soma negatively. Most people did. I have the feeling that that’s in the past as far as Prozac is concerned, that there isn’t that uneasiness, that sense of disease about change.

KRAMER: No. I think there’s some uneasiness, but there’s a complicated relationship between Prozac and Soma. Because Soma is almost externally imposed by the culture, it’s addictive, it sort of is desirable in itself, creates desirable feelings to it immediately, and it induces conformity. Prozac, I would say, is conformist in a more complex way. It may produce, to the extent that it works in the way we’re discussing, it may produce people who conform to a certain social norm, but that norm is to be assertive, self-interested, not communitarian. You know, it really creates this dominant strain, if that’s what it does. So it’s funny, it’s not a conformity-inducing drug, even though the effect is to move people in a direction that society values.

HEFFNER: Well, but that is, in itself, quite considerably a conforming pattern.

KRAMER: Yes, it is. It is conforming without inducing submissiveness.

HEFFNER: Clinically, what do you have to say about Prozac? You’ve observed it now for more years.

KRAMER: Well, of course, all these drugs look more troublesome, you know, down the years for many reasons. One is, as a drug, if medicine is successful, we expand its use to a wider and wider population of people, until it finally comes to people where the, you know, the utility of it is minimal. And I think also because we do get a longer list of side effects over time. I think Prozac is still a very, very useful drug for, you know, what I think are its central indications, namely: minor and chronic depression, depression characterized by certain odd features like eating and sleeping too much rather than too little. I don’t think it’s really been surpassed by the companion drugs, but I think it will be.

HEFFNER: I was going to ask about that. The other drugs of choice. Is there…

KRAMER: Yeah, I think the treatment of depression has become more interesting and more complicated. I think all the other drugs you may have heard about, Wellbutrin and Luvox and Paxil and Zoloft and Remiron, are interesting medication. I think there is more, since the giving of antidepressants is more accepted, there’s been more fiddling and experimenting so that doctors are more comfortable with giving combinations of medications. So the treatment of depression with medication, with medications has become more of an art. It has more complexity, more of the qualities of psychotherapy. It’s just become a more interesting practice altogether. But I don’t think there’s any sort of breakthrough where the moral issues raised by treatment with antidepressants has changed over the past three or four years.

HEFFNER: But hasn’t there become a much more widespread, a much larger base population of physicians who are prescribing?

KRAMER: Yes. Yes. I think, you know…

HEFFNER: Does that concern you?

KRAMER: It does concern me. I think that the good news is that, in the past, depression has always been under-treated even where it’s diagnosed. And it certainly is under-diagnosed as well. Now, we’re not talking about these marginal cases that most resemble personality change; but serious, major depression is under-diagnosed. Where it’s diagnosed, it’s under-treated. And it’s harder to under-treat with these newer medicines. It seems like there’s more of a one-dose-fits-all quality, and then, I think once doctors see patients improve they have some kind of yardstick. Internists, I’m talking about, and GPs and obstetricians and so on. And so then they can tell when a person’s had a partial response, and refer that person on to a specialty mental health sector or a psychiatrist.

HEFFNER: What’s your own feeling about general practitioners, internists, people who aren’t trained in psychiatry, prescribing?

KRAMER: Well, as I say, I have two thoughts about it. One is, they do the work. They have always done the bulk of the work, studies going back 30 or 40 years. The odds of some of the mentally ill seeing a psychiatrist are quite low. I mean, most of these people are treated in the general population. And the better the internists are at diagnosing and treating depression, the better it is for everyone.

On the other hand, there are some very disturbing studies showing that if you just treat depression (which is one of the most treatable mental illnesses) with medication and do nothing else, people’s quality of life continues to deteriorate. Look a few years down the road at people treated in HMOs where the doctor tends not to be a psychiatrist, there tends to be a little psychotherapy, poor follow-up. And people with this eminently treatable illness, depression, tend to look worse off a couple of years down the road. And that shouldn’t be the case. I mean, we are really able to treat depression.

HEFFNER: Despite the use of the drugs.

KRAMER: Yes. I think there is a cynical use of these medicines by insurers, that they’re, because, however expensive they are, they are cheaper than giving psychotherapy. And because there’s a sense that internists, in a way, are less worrisome practitioners than psychiatrists or psychologists.

HEFFNER: Explain that.

KRAMER: Well, I think the insurance companies believe there’s what they call a “moral hazard” to mental illness: that people will go and get treatment for it whether they need it or not, they’ll be treated indefinitely. Studies don’t show this to be the case, but they’re worried. They don’t believe their own actuarial tables when it comes to mental illness. And maybe they just cynically are willing to under-treat mental illness. And the result is that these drugs, which I think can do a lot of good, are used without accompanying psychotherapy, without adequate evaluation before the medications are used, without adequate ongoing follow-up. Instead of diminishing suffering, they’re used to allow suffering to continue.

HEFFNER: In a recent story in The New York Times there was reference made to “arrival to Prozac”; at least that’s what the headline, the cutesy headline, indicated. And it talked about “natural rival” in Germany, plants, being recognized as containing antidepressant chemicals. What’s your…

KRAMER: Yes. This is a common herb, a weed, I guess, called St. John’s wort, which seems to be useful for minor depression. Of course, no one really knows. There was a good review study done about two and a half years ago in the British Medical Journal of all the careful studies of the use of St. John’s wort. And they said, well, it looked like maybe it worked, but the quality of the studies wasn’t very good. And in particular when the herb was used opposed to conventional antidepressants, the conventional antidepressants were given in very low doses, doses that are not used in this country, which would be, in effect, under-treatment. So there wasn’t really a fair comparison.

I think nobody knows. But if I had to guess, I would say probably there is an active ingredient in St. John’s wort that is like a, maybe like a mild form of a drug that exists in Canada called Molindone, which affects a number of pathways in the brain at once. I mean, speak about a scattershot or dirty drug, this St. John’s wort affects serotonin, dopamine, norepinephrine, the pathways that the antianxiety drugs hit. So I think it may be effective. Not much is known about it. And, for various reasons, I haven’t had occasion to use it.

There are certainly careful colleagues — Norm Rosenthal was quoted in The New York Times as a good researcher, in Maryland, — who say that they’ve had good results with St. John’s wort. And it certainly is less expensive than antidepressants.

HEFFNER: What do you foresee as the future of psychopharmacology?

KRAMER: I think psychopharmacology will get very complex and subtle. I foresee very difficult moral issues arising from psychopharmacology. For instance, if we suffer a trauma, we are at risk to suffer depression. And that is through certain biological pathways. What if you could interrupt that transmission? What if a person could suffer a trauma, and you could give that person a medication so that he would never feel the biological effects of the trauma? What if a child’s, a five-year-old child’s mother died, and you’d say, “Well, that child’s a great lifetime risk for depression.” The greatest risk for depression is probably a loss of a parent young in life. What if you could give that child the medicine that would interrupt that biological cascade so that the child never felt the biological concomitance of grief, and therefore was spared depression later in life? Would you want to give that medicine?

HEFFNER: Well, of course, I couldn’t help but think when I was reading your new book, Should You Leave?, which you were exploring, as you say in the subtitle, intimacy and autonomy and the nature of advice, I couldn’t help but wonder about Prozac or antidepressants in the kinds of normal situations that you were describing, and the grief that you talk about in terms of the trauma of the death of a parent perhaps.

KRAMER: Yes, what if medication substituted for intimacy? I think that is something that links these books. What if the sorts of feelings that we’re biologically programmed to feel when we are in adequately complex and trusting mutual relationship can now be obtained through other means? What does that do to us and our goals? Certainly it makes us more autonomous, but it certainly robs us of a certain drive for intimacy.

HEFFNER: Would you make a bet along the lines as to whether that, in time, will be part of the future of psychopharmacology?

KRAMER: I guess I would make that bet. I’d say that we will have options other than turning to other human beings for certain affective states. And I think it’s going to be interesting to see how we use that potential if we have it.

HEFFNER: It’s interesting to me that you say it’ll be interesting, because I know from the last time we spoke it’s something that concerns you very much.

KRAMER: Yes. I mean, my values are, I guess, for a psychotherapist, old-fashioned values. That there really is something to be said for staying where you are, struggling with your circumstances, and finding redemption through value and relationships. And I think that posture is very much under attack. And it’s not just under attack from medication; it’s under attack from medication because medications allow a person sometimes to get those very things which society otherwise demands.

HEFFNER: But society does demand redemption. And I thank you very much for joining me today, Peter Kramer, and recommend, of course, both your new edition with your new afterward of Listening to Prozac, and, of course, Should You Leave?, your newest book. Thank you for joining me again today.

KRAMER: Thank you.

HEFFNER: And thanks too, to you in the audience. I hope you join us again next time. And if you would like a transcript of today’s program, please send $4 in check or money order to: The Open Mind, P.O. Box 7977, FDR Station, New York, NY 10150.

Meanwhile, as another old friend used to say, “Good night, and good luck.”

N.B. Every effort has been made to ensure the accuracy of this transcript. It may not, however, be a verbatim copy of the program.