Ordinarily Well: The Case for Antidepressants



My Sins

IT WAS IN medical school, on my internal medicine rotation, that I first sat with men and women who suffered depression at the deepest level, the depression documented by Albrecht Dürer in prints, Pablo Picasso in oils, and Max Hamilton in his rating scale. On those wards, these patients were not rare. Thin, immobile suffering souls, prematurely aged, they had the classic depressive habitus, the attitude or physique of the disease.

The rounding doctors found melancholic patients difficult to interview. They spoke slowly and repetitively. We trainees set stethoscopes to their chests, checked the IV lines, and left the room. When a depressed woman—Irma—did not answer his questions, the resident asked me to see what I could elicit.

Other medical students excelled at reading cardiograms. I could sit with silence. With Irma, I ventured the occasional comment: The pain is too great. There’s no point trying. At psychiatry rounds, where patients were interviewed with us there, I had seen this approach attempted.

Irma responded, if sparingly. A husband had died, and then a daughter, long ago. Life ended then. Now Irma had heart disease. She was content to die.

What was remarkable was Irma’s coherence. She was not paranoid. She was not hallucinating. She was depressed, although that word hardly captures the bleakness. To speak, she had to overcome interference from a brain that transmitted a single message, despair.

Irma lived with a sister who on Irma’s good days brought her to group sessions at a mental health center. Irma had never taken medicine.

I was barely off the streets, a student of history and literature. We speak of impressions being seared into memory.

I made my report: resigned, but not suicidal. Irma had consented to treatment for heart failure.

I doubt that the rounding team considered antidepressants. Attention to mental illness was not the routine, and besides, tricyclics affected heart rhythm.

Later, on my psychiatry rotation, I saw depleted depressives in number. I trained on a service of the Massachusetts Mental Health Center, a community hospital in the state system, staffed by eminent psychotherapists. The ward housed many Irmas. In the activity room, they sat still, distinguishable from catatonic patients only by their hand-wringing.

Almost twenty years after Kuhn’s discovery of imipramine, Boston doctors treated these patients with psychotherapy alone. Otherwise, depression was allowed to run its course.

Mass Mental was under the sway of an éminence grise, the psychoanalyst Elvin Semrad, a Midwesterner with a knack for coaxing sense out of psychotic patients. In the recollection of a classmate of mine who did a residency at Mass Mental, Semrad saw medications as “chemical straitjackets” and intrusions on patients’ autonomy. People needed to inhabit their illness until they felt safe enough to abandon it.

There was irrational confidence in the other direction as well. Leading psychopharmacologists had founded a medical-model service. There, the prevailing belief was that the small collection of available antidepressants and antipsychotics, Largactil’s progeny, could cure anything. Often, patients improved and went home. But the medicines could cause movement disorders that mimicked Parkinson’s disease. The sight of zombified patients served to justify the skepticism of psychiatrists from the psychotherapy-oriented wards.

Presently, the two cultures would make contact, with trainees from my generation as a moving force. Having seen successes with pharmacology, they could not let ill patients on psychotherapy services suffer. Where at the start of my cohort’s training, prescribing was scorned, toward the end, residents went to court to force patients to take medications by injection. Brigadoon vanished.

I left Harvard for a medical internship at the University of Wisconsin, followed by a psychiatry residency at Yale. Both balanced psychotherapy training with biology research. Prescribing was understood as an art. Nowhere did I see the volume of end-stage depression I had encountered in Boston—nor have I ever again. And in thirty-plus years of outpatient practice in Providence, not one of my patients has begun with or, to my knowledge, moved on to classical, paralyzing melancholy. Perhaps there is a single exception, an elderly, demented, alcoholic man who required electroconvulsive therapy.

Where are they, Irma and her fellows?

This chapter stands as further confession. I have said that clinical understanding must, where possible, find grounding in formal evidence. But if I am honest, there are reasons, beyond the numbers, that I would find it hard to believe that antidepressants do not work. Among them is an apparent decrease in the end-of-the-line depression that was familiar in my medical-school years.

I know of no data on this topic. The Public Health Service conducts surveys on mental illness, but the prompts are too general to reveal trends in categories like severe depression. Lacking better evidence, over the years I have asked medical students, senior colleagues, and mood-disorder specialists what they see. Their response is uniform: little end-stage depression, much less (say the oldest doctors) than four or five decades back.

Asked about their gravest cases, med students say, A patient who had been doing well in treatment lost his job, could not afford his medicine, resumed drinking, missed his clinic appointments, and after four months was brought to the emergency room by the police. Paralyzing melancholy has become an element in a tale of treatment interrupted.

One colleague specializes in neuromodulation, the application of electricity or magnetic current to the brain. The treatments—ECT, transcranial magnetic stimulation, and deep-brain stimulation—are reserved for the most seriously depressed. In a series of sixty consecutive patients referred for assessment, she found only one with the paralyzing condition I asked about. His depression was complicated by multiple small strokes evident on a brain scan.

I doubt that I would have published this chapter without one final piece of testimony. In 2014, I attended a talk by Anthony Rothschild, a researcher at the University of Massachusetts who is arguably our premier expert on psychotic depression. It is crucial to recognize this condition—depression accompanied by hallucinations or delusions—because it tends to respond to antidepressants only when a second drug, an antipsychotic, is added.

Tony interviews severely depressed patients regularly. I asked about nonpsychotic depression: Did he still see classic, immobilizing melancholy?

No, he said. There’s much less of it. His thought was that primary-care doctors nip depression in the bud, enough to make a difference. He spoke of depression as a progressive disease. People used to move from depression to severe depression to that paralyzing state. Since the 1980s, with the advent of easier-to-use antidepressants, often the downward progress is interrupted.

We still see psychotic depression. Doctors don’t diagnose it well, so it’s not treated complexly, and it worsens. The shift is in the prevalence of end-stage nonpsychotic depression, a worse phase of the straightforward depression that does often respond to simple treatment.

Over long intervals, many things change. We’ve grown increasingly aware of dementia, drug abuse, and post-traumatic states; we see them as separate from mood disorder. We may have made depression a more limited category, one skewed toward healthier people.

There are no data, and if there were, comparisons over time might remain unreliable. Still, I’m guessing that the change—fewer like Irma—is real. With the deinstitutionalization of mentally ill patients, we should all know people with severe melancholic depression. For the sweep of human history, they have been with us, sufferers with wasting bodies, tortured eyes, and downturned gazes. They were seen at the church and in family homes as part of communal life. And now—rarely.

As I say, I am engaged in confession. Unlike randomized trials, my observation affords scant protection against confounding factors. Perhaps my informants tell me what I want to hear. It’s only that the shift seems so large, so general.

I know better than to insist on this line of thought. Diseases come and go. Often, doctors cannot explain why. Anorexia has fluctuated in incidence: high in the 1930s, low in the 1950s, with steady increases for decades after.

If treatment plays a role, it’s not only antidepressants that have impacted depression. Altogether, we are less willing than we once were to let mood disorders fester. Psychotherapies aim to target depression directly, to interrupt episodes. The adoption of lithium salts to moderate manic depression is the great psychiatric success story of the twentieth century. Surely making inroads against bipolar disorder influences the frequency of end-stage depression.

When severely depressed patients enter a hospital, they are treated vigorously. We are less likely to see them sit in their misery, week after week.

Still, my impression is that end-of-the-line depression is less common in part because—haphazardly, with many a case missed altogether—we treat depression early, generally with antidepressants. Even when it fails at symptom reduction, prescribing may work preventively. Certain studies in psychiatry have conclusions that take this form: A bad outcome, like memory loss, correlates with the length of time a woman is depressed—but the correlation is more robust if you subtract the weeks that she was medicated with antidepressants, without regard to whether the patient responded. Time in treatment confers the benefit.

Do we, now and then, only change the form of the disease, creating mobilized depression? We must, and sometimes to the good. I see patients, still moody, who can raise their children and go to work. As with cancer, with depression we have turned terminal cases into chronic ones. In the worst instance, like the Roman general Fabius the Delayer, prescribing doctors beat a measured retreat, slowing the enemy’s advance.

If that delaying effort counts, then the practice that I observed at Harvard, forgoing medicine and letting depression take its course, was, for all its idealism, barbaric. Irma and her fellows were psychiatry’s pride then and its shame now.

I was no hero in this narrative. Despite having seen Adele respond to imipramine, I remained intent on my teachers’ wisdom, retaining hope that psychotherapy would heal all ills. Recovery on medication seemed second-best. What shifted first was my sense of the required pace of progress. I hated to see patients suffer.

When I say that the attack on antidepressants presents dangers, my perspective begins with patients afflicted by severe classic depression. On occasion, our arguments about efficacy will sound bloodless. We must not find them so. Throughout, we must see people in pain.

Imagine Irma after her first pregnancy, on the death of her husband, on the death of her daughter. Imagine Irma at critical junctures, struggling with progressively more disabling episodes of mood disorder. Might medication have slowed her slide? While her depression was still mild or moderate, should she have been offered a trial of antidepressants?

Surely she should have—unless they do not work.

Because I do not see her like, I believe that they do.

The chain of reasoning that creates that sentence contains a dozen weak links—I have conceded as much. But then, every doctor approaches research evidence from a complexly shaped perspective. I work under this influence, time spent with depression when prescribing was taboo.

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