What antidepressants are saying 30 years after the publication of ‘Listening to Prozac’

In 1993, I published “Listening to Prozac,” a book that grew out of my clinical experience prescribing what was then a new class of medications, ones thought to moderate depression through their effect on the way that the brain handles the neurotransmitter serotonin.

Some of my patients had reported marked favorable reactions to the drugs — first Prozac and, soon after, Zoloft. On medication, the patients were more confident, less anxious, and less pessimistic. They felt better than they had even before the episode of whatever it was that we were treating, depression or increased obsessionality. One patient said that she was herself at last, as if, absent the formulation of the new drug, she would never have been herself. In the book, I tried to explain how those effects might occur and then to discuss implications for medical ethics and society at large. How malleable is the self? How open are we to technologies that might change it?

“Listening to Prozac” became a national and international bestseller and has remained in print ever since. The book is now available in a 30th anniversary edition with a new foreword and afterword in which I update the science and discuss changes in the cultural status of antidepressants. In brief: We rely on them more but respect them less.

When I wrote the book, the responses that my patients reported required explaining. In the early 1980s, I had served in the federal government, heading an agency that oversaw a broad range of mental health research. I turned to the experts I had worked with then, in fields ranging from cell biology to animal ethology, in hopes of understanding how compounds developed to treat major depression might affect personality. For the book, I drew on that research and went on to explore implications for medical practice. If these or future drugs could moderate a trait like shyness that, although not abnormal, is uncomfortable and socially disfavored, should doctors use them to that end, engaging in what I called “cosmetic psychopharmacology”?

I predicted that the new medications would lead to new habits of prescribing, perhaps via what I called “diagnostic bracket creep,” apparent justification for treating ever less severe forms of depression. But even I did not anticipate the magnitude of Prozac’s impact. In the late 1980s, each year perhaps one American in 50 received a prescription for an antidepressant, and the duration of treatment was mostly a matter of months. Recently, usage has shot up to more than one in seven, and some patients stay on medication for decades.

Expanded adoption and the passage of time have brought pushback over antidepressants in their main role, treating mood disorder. Patients in antidepressant survivor groups complain in social media about adverse effects from medication. Within the professions, an antipsychiatry movement has coalesced, claiming that antidepressants are little more than placebos with side effects and that the brain’s use of serotonin doesn’t play a salient role in depression. I discuss these objections in detail in the new essays in “Listening to Prozac,” and also in my prior nonfiction book “Ordinarily Well.” My view is that we have been fairly lucky with the medications in terms of side effects and very lucky in terms of main effects. They have relieved suffering in millions of patients.

Perhaps unexpectedly, about better-than-well results — effects on temperament — there is less dispute, and again, here, I seem to have underestimated the phenomenon. Research conducted after I wrote “Listening to Prozac” suggests that it and similar antidepressants are especially effective in moderating introversion and a personality trait called neuroticism, an amalgam of negative thinking, uncomfortable self-consciousness, and emotional vulnerability and instability. The personality effects may be more pronounced than the antidepressant effects and may be partly responsible for them. No one disputes that serotonin is implicated. Similar change takes place throughout the animal kingdom, where manipulating serotonin can predispose males to alpha status. When Prozac makes its way into the water supply, which sadly, it does, regularly, and in large amount, certain fish can become too bold and, therefore, vulnerable.

Today, the question I’m most asked about “Listening to Prozac” is whether, over the years, I have continued to witness dramatic good responses to antidepressants, the outcome that my patients and I had called “better than well.” The answer is: less often — but not for the reasons you might think.

Once “Listening to Prozac” became a best-seller, my clinical practice changed. I saw patients in a private office in Providence, Rhode Island, and had enjoyed treating patients with a broad range of diagnoses.

But whatever my intentions as an author — I thought I had been writing about the reframing of the modern sense of self — readers saw my book as a resource for understanding depression, and they came to me for help with complex and often hard-to-treat forms of mood disorder. Try as I might to keep my patient mix local and diverse — I liked being a small-city doctor — the practice became ever more national and specialized.

People sought me out because they had done poorly elsewhere. Rarely was I the first doctor to put a patient on a drug like Prozac. Only occasionally did I treat first and second episodes of depression, uncomplicated by other psychiatric conditions.

My experience represented an extreme version of what was occurring throughout psychiatry. If a family doctor wrote prescriptions for antidepressants and patients found relief, as happens in the great majority of cases, they might never see a mental health specialist. Like me, my psychiatric colleagues were largely treating the remainder, patients who were not helped, or helped only in part, by simple prescribing.

When I worked in public health, starting in the Carter administration, one of our goals had been to get primary care doctors to recognize and treat depression. Prozac — easier for doctors to manage than prior antidepressants — made it happen. It was those generalists who now saw patients gain assertiveness and social competence.

Meanwhile, the medical professions’ understanding of mood disorder changed. Depression is defined by a cluster of symptoms — deep sadness, obsessive self-blame, slowed thought and speech, problems with eating and sleeping, suicidal thoughts, a loss of the ability to experience pleasure, and more. In the 1980s, if a patient’s episode of depression resolved, if her sleep and appetite and energy improved and she returned to being passive, pessimistic, and socially withdrawn, the medication had done its job. But having seen patients on the new antidepressants do better across the board, doctors now often took melancholic temperament to be residual illness.

And residual illness can be harmful. One of the great changes in the past three decades is in doctor’s awareness of chronic low-level mood disorder and the risk that it carries not only for suicide but also for routine bad outcomes in life, including limited success in love and work. A once-sharp division, between depression as illness and depressive temperament, began to blur, so that some of what I had understood as personality change became incorporated into doctors’ image of routine recovery from depression. This diagnostic bracket creep struck me as mistaken conceptually — think of those bold fish — but sometimes justified clinically.

Nor were patients neutral on this topic. Surely some of what’s controversial about current prescribing practices — long-term medication use — arises from patients’ preferences. Even between episodes of mood disorder, some patients who are prone to depression find that they do better on medication and worse off it.

I stopped treating patients five years ago and have since been writing full time. Until then, I continued to see dramatic favorable responses to antidepressants. But I more often heard or read about them. Readers often wrote, and still do write, to tell me that they resemble this or that patient in my book’s case vignettes. And people who find themselves more socially competent on medication sometimes share their experience in the press or on social media.

Not long ago, I was asked to endorse an insightful nonfiction book by the journalist Rachel Aviv. She expresses skepticism about medication, and often about mental health care altogether. As a journalist, Aviv was known for publicizing the difficulties that certain patients report when coming off antidepressants.

But Aviv — so she writes in the book, Strangers to Ourselves — had a life-changing response to one of Prozac’s younger cousins, Lexapro. After long hesitation, when on the drug, Aviv decided to get pregnant. Next, for the sake of the fetus, she took herself off — and then could no longer recall why she wanted to have a child. Back on medication, she found motherhood natural again. Subsequently, Aviv found herself a better parent to her children when on medication although, while writing her book, 10 years into her acquaintance with the drug, she was back to tapering it.

I continue to collect stories of personality change on medication. Some instances, as in Aviv’s case, are experienced as mixed blessings. The welcome upside is tarnished by concerns about what it means to be on medication, for mind and body—and for the patient’s identity. How complicated the interactions are between medication use, life choices, and functioning in the family! These patient narratives reassure me that 30 years on, the question at the heart of “Listening to Prozac” remains fresh and relevant, the one about medication and the nature of the self.

Peter D. Kramer is the author, most recently, of the novel “Death of the Great Man.” He is an emeritus professor of psychiatry and human behavior at Brown University.