I AM NOT prone to spirituality. We joke in my family that swimming is our religion. We must be in the open Atlantic, in Massachusetts, before Memorial Day and after Columbus Day, and not just for a second.
Religion goes beyond the regularity of observance. The ocean enforces a sense of proportion, awareness of our insignificance. It demands virtues, courage and perseverance. Swimming has an aesthetic, the up and down of it, the being in nature, primitive and sublime. Swimming has its ecstatic and contemplative aspects—in mind and being, the oscillation between focus and unself-consciousness. Swimming testifies to love of family, the family at play. Perhaps that’s the real religion. Family is sacred.
I make this confession—for a secular person, I do seem to confess often—as a lead-in to saying that for me the clinical encounter is a sacrament. It would not be wrong to apply that (metaphorical, half-serious) term to the moment of prescribing. I want to be deeply aware of what I bring to it. The patient and I are vulnerable, in touch with great forces.
Here we are, Nora and I. Or the patient may be Stephan, Olivia, Caroline, or another. The time comes to choose. What I bring to bear is not narrow evidence, not one single dispositive research result. Better: What bears on me is a life in psychiatry, a life within a tradition of thoughtful lives.
The experience is of being influenced by encounters with patients and interchanges with colleagues and teachers, all those observations, direct and indirect, of patients on medication and off. The experience reflects years of reading, of seeing antidepressants work in the consulting room and in the literature.
When I review medication’s successes over a half century and more, it will sound, forgive me, like a litany—a litany of evidence.
But imipramine worked in Roland Kuhn’s hands.
It worked in the randomized trials that followed hard upon his discovery.
Antidepressants worked in the first meta-analysis, by Gene Glass.
They worked in the major NIMH trial, benchmarked by imipramine.
By the numbers, antidepressants showed efficacy in the first major debunking study, “Hearing Placebo.”
The first effort in evidence-based psychiatry, reviewing dysthymia treatment, found antidepressants effective at a high level.
If read carefully, even drug company research—shaky in more ways than one—demonstrates efficacy.
When the severity hypothesis resurfaced, researchers reviewed our largest collection of drug trials for mild-to-moderate major depression. Antidepressants worked there.
Antidepressants diminish neuroticism.
Antidepressants confer overall well-being. They show benefits, in quality of life, even in people who continue to suffer symptoms.
Antidepressants work for general medical patients, patients with neurological or cardiac ailments who are merely liable to depression—interrupting episodes promptly when they appear.
Antidepressants prevent the onset of depression in patients with few symptoms and the recurrence of depression in people with long-standing mood disorders.
For clinic patients, three-fourths of depressive episodes and more will respond to antidepressant treatment.
Even hard-to-treat chronic patients—almost all, if they hang in—will achieve remission on antidepressants, over time.
When depressed patients respond to medication, keeping them on it will spare them half or two-thirds of the episodes they would otherwise be liable to—for any length of time that’s been studied.
That list may give a distorted picture of how information arrives. It comes piecemeal. Since the seventies, I’ve seen antidepressants in action and then read journals for guidance. I seek out a study, or it crosses my desk: Should it cause me to revise my views? What are the details? What confounds is it subject to?
There can be seismic shifts in medical knowledge. Peptic ulcers were long thought to be caused by temperament, stress, and spicy foods. In the 1980s, research confirmed an unlikely competing hypothesis, that bacterial infection plays a leading role.
The antidepressant story has not been like that. Information has accreted, most of it supportive of prevailing opinion. There has been no emperor’s-new-clothes moment—no revelation of myth, to use Per Bech’s word, regarding the efficacy of antidepressants.
As for how well antidepressants work, in the numbers needed to treat, we’ve heard a drumbeat of 4s or 4-to-5s. I see those numbers needed to treat—and even occasional higher ones—as tickets in, indicators of overall efficacy.
That’s because, with the efficacy estimates, there’s headroom. Drug trials are no longer run on the people medicine helps most reliably. Our rating scale is at once too inclusive and too narrow, emphasizing bodily symptoms and missing effects on neuroticism and overall well-being. In the design and conduct of our trials, incidental factors, good and bad—minimal supportive psychotherapy, baseline score inflation—pump up the response rate in the control arms, while lessebo effects and the use of low doses make medications look less robust than they do in office practice. That’s all before we consider problems with additivity.
Think of Allison, in her interviews with Verna, the research subject who endorsed every item on the Hamilton scale. Contrast Allison’s vantage to our internist’s—Viola’s—in her observation of a patient like Verna. Who contributes better information to our impression of what drugs do?
Formal research has its role: to pick out treatments that are inherently effective. But for telling us how much, overviews of randomized trials will not always have the advantage over doctorly experience. The doubts about antidepressants’ worth simply don’t seem serious.
The notion that depression is highly responsive to placebos—responsive in any important way, over time—strikes me as implausible. Here I rely on the feel of the disorder, its ponderousness. I rely on hours spent with Adele and others like her, patients whose depression does not budge in response to promising dramatic treatments but that eases with antidepressants.
It’s true that psychiatrists are agnostic priests. We are aware that the Pharma trials are shameful, ethically and scientifically. We are aware that our understanding of medications is incomplete. We feel obliged to protect our patients from unknown harms—not demonstrated but still imaginable. That’s the contribution of papers on the nightmare scenario, papers that, however limited in scientific merit, give name to dark fears that are unavoidable in psychiatric practice.
Yet there are issues about which I am not agnostic. I do not want to go back to the days of Ray Osheroff and Irma and, when his treatment was psychotherapy only, Robert Liberman. I think of Moira, gloomy, reclusive, and prone, despite psychotherapy, to recurrent low-level depressive episodes. Moira’s life is better for her having discovered medication, and in a psychiatrist’s memory, there will be many Moiras.