On The Empire of Depression by Jonathan Sadowsky

Among the most important early works in the social history of medicine were histories of mental institutions. Here, in often great detail, historians wrote of seemingly barbaric procedures — such as insulin shock therapy, electroconvulsive therapy (ECT) and lobotomy — that had less to do with helping patients than keeping order within the hospital. These revelations, and similar treatises on other aspects of medical history, threw into question the earlier “Whig” history of benevolent doctors who continually made progress in the diagnosis and treatment of disease.

Although many recent scholars have provided clarification and nuance to these critiques of psychiatry, there remains a skepticism about the value of treatments, such as the selective serotonin receptor inhibitors (SSRIs) for depression, writes Case Western Reserve University historian of medicine Jonathan Sadowsky in his thoughtful and nuanced new book, The Empire of Depression.

I am especially interested in what Sadowsky has to say. As a historian of medicine, I am very familiar with critiques of psychiatry and its therapies, both past and present. And as an internist, I have many patients who suffer from depression. I often ask myself how quickly I should suggest a trial of SSRIs for people with symptoms such as sadness, tearfulness and loss of pleasure.

Throughout The Empire of Depression, Sadowsky pushes back as hard as he can to carefully reintroduce a positive narrative within psychiatry. What if SSRIs — so-called happy pills — actually make people happy? And, if so, why is there such reluctance to accept this?
What if so-called happy pills actually make people happy?

The Empire of Depression begins with another topic: the social construction of disease. Here Sadowsky provides a master class on this perennial and important topic in the history of medicine. Are diseases pure biological entities or do historical actors in specific time periods describe and label them based on social and cultural factors? In the case of depression, it is worth comparing it to a condition known as melancholia.

Melancholia, which stretches back at least as far as the ancient Greeks, was “marked by dejection, fear without cause and sometimes a delusional break with reality.” Shakespearean characters, Sadowsky argues, were notoriously melancholic, as with Macbeth’s “weariness, despair and inability to find anything of value in life.”

So are the two conditions the same? Yes and no. Although doctors specifically began to replace “melancholia” with “depression” in the early 1900s, melancholia was classically a disease of men while depression preferentially affected women. But what both of them shared was that they were diseases of the body and the mind. Patients had psychological woes and physical debilities.

Merely switching the name to depression did not make understanding it easier. Like all diseases, depression was historically contingent. In the postwar Freudian era, depression was “anger turned inward.” The treatment? Psychoanalysis. But with the rise of a biological model of depression and other psychiatric illnesses beginning in the 1970s, the treatment, increasingly, was medication.

OK, so both melancholia and depression were socially constructed. But the last thing that Sadowsky wants to imply with this is that they were not real. Indeed, he approvingly quotes one doctor who said that there is only one disease worse than depression, which is rabies. What Sadowsky’s goal here is to argue that even though a disease may be characterized differently over time, and be susceptible to professional, financial and cultural influences, it is still a disease that makes people sick — very sick. Or, as prominent neuropsychiatrist Nancy Andreasen has written, depression is “a disease like any other.”

Others who would agree with this conclusion are the large number of memoirists who have documented their depression. In a fascinating chapter (“Darkness Legible”), that includes the writings of poet Sylvia Plath, novelist William Styron, writer Elizabeth Wurtzel (author of Prozac Nation) and singer Bruce Springsteen, Sadowsky concludes their work all shares one thing in common: “Their urgent agenda,” he writes, “is to have their illnesses seen.”

The most compelling parts of The Empire of Depression are its assessment of the chemical imbalance theory of depression. Sadowsky recounts the fascinating story of iproniazid, a pill initially given to treat tuberculosis in the 1950s. Gravely ill patients given the medicine became noticeably happier and even began dancing in sanatoriums. Doctors initially assumed patients were simply recovering from their debilitating tuberculosis, but the pill was actually not so great at treating the disease. Eventually they concluded that the euphoria resulted from the inhibition of monoamine oxidase, an enzyme that breaks down neurotransmitters in the brain — including norepinephrine, dopamine and serotonin — in the brain. Concluding that higher levels of these compounds in the brain could potentially successfully treat depression, doctors developed a series of drugs known as monoamine oxidase inhibitors (MAOIs).

But MAOIs had lots of side effects and interactions with other drugs. So researchers developed more precise agents, the most famous of which was Prozac, a selective serotonin reuptake inhibitor that became available in 1987. And they doubled down on the theory that depression was the result of a “chemical imbalance,” a biological abnormality in the brain that the new pills rectified. Could it be that depression — and maybe even melancholia — had just been purely biological all along?

“Doctors who had been on the side of biological psychiatry all along,” Sadowsky writes, “ were having their moment of cultural triumph.”

Much ink has been spilled on the history of the SSRIs and Sadowsky provides a clear and helpful summary. Within five years of its availability, Prozac had been prescribed to five million people. Like iproniazid, it seemed to be a wonder drug. Patients who had been depressed for years felt the oppression that had destroyed their lives for years — what the writer William Styron had called “most closely connected to drowning or suffocation” — was almost magically being lifted.

Listening to Prozac

Indeed, Prozac was seemingly so successful that in 1993, psychologist Peter Kramer published Listening to Prozac, which popularized the “serotonin hypothesis” and told dozens of stores of dramatic recoveries from depression. As an internist with his share of depressed patients who had tried other pills and years of therapy without much success, I took close notice. Had scientists figured out the biological conundrum that could enable me to help my severely — and mildly — depressed patients? It was a very appealing notion and I prescribed SSRIs fairly liberally. Reports that the drugs caused increased rates of suicide in certain populations, particularly adolescents, led me to be more cautious but no less enthusiastic.

But Listening to Prozac was even better known for popularizing two terms: “cosmetic pharmacology” and “better than well.” Was it possible that people who were not depressed at all were popping Prozac and its sister pills in order to just feel better? And, if so, weren’t these individuals somehow frauds, using pills to make themselves into people they were not?

Sadowsky correctly argues that Kramer was ambivalent about these developments. But critics had a field day, arguing that Listening to Prozac was promoting a biological fix for a complicated illness and promoting the use of medications for those who were not actually ill, just dissatisfied with their lives.

This reflexive criticism, in a sense, was reminiscent of the old social historians’ assessment of mental institutions and their treatments. If these hospitals were overcrowded and understaffed, and if they relied on inhumane biological treatments, weren’t they thoroughly reprehensible? Sadowsky and other historians have already taken on this conclusion. For example, in Electroconvulsive Therapy in America, Sadowsky argued that ECT is a actually highly effective treatment for depression that has been unfairly tarnished by its cultural characterizations. In Last Resort, Jack Pressman showed how lobotomy, while misguided in retrospect, actually represented the best science of its day.

So where does this leave us? Is depression caused by a chemical imbalance that is best treated biologically? Readers looking for a definitive answer in The Empire of Depression will be dissatisfied. Despite the seeming success of SSRIs in dramatically improving the lives of many depressed patients, randomized clinical trials have not been definitive about their effectiveness. Antidepressants generally perform better than placebos, but not by much.

But these findings do not bother Sadowsky much. He provides several explanations for why randomized clinical trials have not revealed the good that these medications do. For one thing, clinical trials tend to enroll treatment-resistant patients, who may be less likely to respond to any drug. And, as Sadowsky argues all along, depression is both a biological and psychological disease. Trying to reduce it to one or another is pointless. As such, we should appreciate the advances made in biological understandings of depression but not be surprised that they have not been a magic bullet.

“We should not … have contempt for the hopefulness of biopsychiatry in the late twentieth century,” Sadowsky believes. Rather, we should look at the day-to-day reality. “Millions of people are taking antidepressants and finding them helpful,” he notes, adding “Call me old-fashioned, but I think reducing suffering is good.”

This conclusion will make some readers uncomfortable. After all, the history of medicine is rife with anecdotes about supposedly effective treatments whose worthlessness was proven in clinical trials. But, as Sadowsky says, “Clinical experience matters too.”

As an internist, I certainly agree with this conclusion. So I will continue to prescribe SSRIs for my depressed patients. Not infrequently, when they return for their next visit, they are better. They are happy and I am happy. I’m not sure exactly why the pills worked, but maybe that is OK.

Originally published on medium.com on January 11th, 2021.