It has become fashionable, at least among those impressed by the latest results of neuroscience, to say that Descartes got it backward.  Not “I think therefore I am,” but “I am therefore I think.” The mind is composed of the body.  Brain makes mind possible.

This is not how we experience ourselves. “I feel therefore I am” is probably the first and fundamental experience of self, or at least the experience that makes life worth living.  It is the feeling of being alive.  Depression is the opposite.  It robs existence of vitality and pleasure.  That’s the cardinal symptom of major depression; it can make life not worth living.  Depressed people are about twenty times more likely to commit suicide (Gotlib and Hammen, p. 356).

“Depression is the flaw in love”

A couple of recent books, books that take the neurological basis of depression seriously, see love and its loss as central to the experience of depression.  Because the mechanism of depression takes place in the brain, and because medication and other treatments that work on the brain often help, doesn’t mean that our experience of the world is unimportant.  Most important is loss, above all the loss of love: of being loved, of a loved one, as well as the loss of values crucial to one’s identity, such as the loss of religious belief.*

“Depression is the flaw in love,” writes Andrew Solomon. “It is the aloneness within us made manifest.” (p. 15)  Medication and therapy work not because they take the place of love, but because they make it possible for us to love and be loved.  For what is the good of a more balanced mind if one has nothing of value to do with it?  Generally, this love is of another person, but it can be love of one’s work, or faith.

Stress causes depression among the vulnerable. Surprisingly, humiliation is the greatest stressor, loss is the second. (Solomon, p. 61).  But perhaps they are not so different.  Though we seldom think about it this way, loss is shaming.  After loss we are exposed to the world, naked and alone.  Once you experience a shaming loss, you will never be the same, for you will have learned something about your vulnerability that you may have sensed but never known. 

Most of us, even those with depressive tendencies, have never experienced a major depression.  Solomon’s is the most horrifying depiction of depression that I have ever read (pp. 39-100).  It is not artistic, just brutal and frightening, an account of an obliterating force that destroyed every aspect of his life.  It was far worse than what is called anhedonia, an inability to experience pleasure in anything.  Instead, he lived in a state of horror.  Imagine living for months within the experience rendered by Edvard Munch’s “The Scream.”

Medication and therapy

It is puzzling that experts are still debating whether medication or therapy is the best approach to treating depression, for the best approach is both.  This silly dispute is rooted, I believe, in whether one thinks that the phenomenology of depression, that is, its experience, is central to understanding, or whether neuroscience is enough.  Ellen Frank says that the dual approach is

“the treatment strategy for preventing the next episode of depression . . . It’s not clear to me how much room there’s going to be in the future of health care for an integrated view, and that’s scary.” (quoted in Solomon, p. 104; Frank and Reynolds, 1999)

Why wouldn’t drugs plus therapy be the obvious solution?  Because drugs are relatively cheap; therapy isn’t.  But it gets worse.  The therapies most recommended by so-called authoritative sources are cognitive behavior therapy (CBT) and interpersonal psychotherapy (IPT), which sounds good, but isn’t, for it is another short-term approach (see here). Both are generally referred to as structured psychotherapy, and they really are.  CBT and IPT are readily manualized—that is, capable of being used by relatively unskilled technicians after a short period of training. 

CBT is often completed in as little as twelve sessions, IPT in 12 to 16 weeks.  Basically similar, IPT focuses on affects (feelings), CBT on cognitions (thoughts).  Instead of focusing on “distorted” thoughts, IPT focuses on “distorted” thinking about important people in one’s life.  In neither is there any opportunity to explore feelings and emotions that might lie behind these “distorted” (which can only mean socially unacceptable) thoughts and feelings.  More on what good therapy looks like shortly.

Progress in treatment, less in understanding

There are lots of drugs to treat depression. Here is only a partial list of drugs by class.  Most classes have at least two drugs; there are at least seven SSRIs, and four SNRIs.  Prozac is the most well-known SSRI.    

• Selective Serotonin Reuptake Inhibitors (SSRI)
• Serotonin and Norepinephrine Reuptake Inhibitors (SNRI)
• Tricyclic and Tetracyclic Antidepressants 
• Atypical Antidepressants 
• Monoamine Oxidase Inhibitors (MAOIs)
• N-methyl D-aspartate (NMDA) Antagonist 
• Neuroactive Steroid Gamma-Aminobutyric Acid (GABA)-A Receptor Positive Modulator

Recently, ketamine (also known as the party drug “special K”), and psychedelics, have shown promise, especially since they act quickly, unlike many depression medications.

In addition, there is ECT (electroconvulsive therapy, that is shock therapy); TMS (transcranial magnetic stimulation); and DBS (deep brain stimulation, electrodes implanted in the brain connected to a pacemaker-like device).

The lesson I take from all these medications and treatments is that no one really understands depression very well, and the standard practice is to try lots of drugs, many originally developed to treat psychosis, such as aripiprazole (Abilify).  These drugs are almost always prescribed in combination with other drugs.  The good psychiatrist will keep mixing and matching drugs until some combination works, at least for a little while.

The number of drugs used to treat depression runs into the hundreds when one considers each permutation or cocktail, often three or four drugs, as a different treatment.  Nothing quite like this exists for any other disorder.  It means that we simply don’t understand the disease, if that’s what it is.  If it’s an existential crisis (whatever that is exactly), then all the drugs in the world are going to help only a little bit.

In any case, don’t imagine that increasing serotonin is the solution.  We still don’t know how it works, and increasing serotonin levels in the brain via SSRIs (still the largest class of antidepressant drugs) is not magic.

When you raise serotonin levels and cause certain serotonin receptors to close up shop, other things happen elsewhere in the brain, and those downstream things must correct the imbalance that caused you to feel bad in the first place. The mechanisms, however, are completely unknown. (Solomon, p. 113)

“This serotonin thing,” says David McDowell of Columbia University, “is part of modern neuromythology.”  It’s a potent set of stories. (Solomon, p. 22, communication with author)

An expert in depression becomes suicidally depressed

When a young professor in neuroscience and psychiatry at Stanford becomes suicidally depressed, what does she do?  She develops a close relationship with a good therapist.   She found one of the best, who combined medication with traditional talk therapy, a combination that is becoming rare.  She sees him weekly or more often and has maintained the relationship over decades. “Over the next many years . . . I saw him at least once a week; when I was extremely depressed and suicidal I saw him more often.” She will remain on medication for the rest of her life (Jamison, p 88).

Jamison received a type, level, and degree of psychotherapy unavailable to 99.9% of the population, a point she never mentions.  What she mentions is how therapy saved her life, and how much therapy she had.  During one particularly difficult time, “I was seeing my psychiatrist two or three times a week.” (p 111)

Hardly anyone can afford the quality, intensity, and duration (essentially her entire adult life) of psychotherapy Jamison received.  Most don’t need it, but most need far more than they get.  If they’re lucky and are able to work the health insurance system (and severely depressed people can’t do that), their insurance will authorize CBT or IPT for a few weeks. They may be adequately medicated, but their medication will not be well monitored and their cocktail remixed as often as necessary.  Medication is cheap compared to therapy.  But they will never receive the quality and quantity of care Jamison received.

Few will. That is reserved not merely for the relatively wealthy, who can pay $350 an hour (actually about 45 minutes) to talk with a psychiatrist who listens and doesn’t just medicate.  Jamison was known in the field, giving her access to the best psychotherapists in the United States.  She could instead have worked with a medicating psychiatrist and an experienced psychotherapist without a medical degree.  It makes little difference as long as the psychotherapist is patient, skilled, and utterly reliable.

            Depression is the leading cause of disability.

Depression is the leading cause of disability for people in the United States between the ages of 14 and 44 (see here).  Worldwide, including the developing world, depression accounts for more of the disease burden, as calculated by premature death plus healthy life-years lost to disability than anything else but heart disease (see here).

Most insurance plans cover only short-term structured, therapies, such as CBT or IPT.  Of course, most depressed people don’t need the level of care Jamison did, but almost all need more than they get.  And Jamison’s account of her superb treatment serves an unstated purpose, the purpose served by all utopian speculation.  The impossible and unavailable is a measure of how far short we fall, and how far we have to go.** 

It’s not difficult to imagine a psychological support system that, without providing a lifetime of psychiatric care, would recognize how much support the severely depressed need, and care enough to provide it.  However, as Frank suggests, we seem to be going in the other direction.  A medication-only solution is driven not only by cost pressures but by a neurological way of thinking that has transformed the depressed person into a depressed brain.  Many sufferers now refer to their depression as a “chemical imbalance.”  It’s true, but it’s not the whole truth, and the whole truth seems to be drifting further and further away.

Postscript

A Canadian study estimated that providing CBT to every person in Ontario with a major depressive disorder would cost the provincial government about $68 million Canadian dollars in 2021.  The CBT would be limited to 8 or 16 sessions. This is the least effective therapy available.  On the other hand, $68 million is cheap, and combined with medication it’s likely to help some, measured by what the study calls QALY (quality-adjusted life years), whatever that means in real life (see here).  Providing high-quality care (which CBT is not) for large numbers of people suffering from major depressive disorder is not impossibly expensive, though it would not be cheap.  It’s all a question of values.

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Notes

* In “Mourning and Melancholia,” the classic work on the subject, Sigmund Freud draws an important distinction.  Mourning is normal and grieves for the lost object.  Melancholia (depression) treats the lost object as part of itself, turning against the self for its loss.  My sense is that the ego always treats the lost object as part of the self.  Why some mourning becomes endless remains unclear.

** Jamison’s more recent Fires in the Dark (2023) adds little to her argument.  It reads more like an extended postscript.  In an interview with The New York Times, she said “If I could have subtitled it ‘A Love Song to Psychotherapy,’ I would have.”  (see here) 

References

Ellen Frank and Charles Reynolds, “Nortriptyline and interpersonal psychotherapy as maintenance therapies for recurrent major depression,” Journal of the American Medical Association 281, no. 1 (1999). 

Freud, “Mourning and Melancholia.” Standard Edition 14: 243-258. (original 1917)

Ian Gotlib and Constance Hammen, Handbook of Depression, 3’d edition.  Guilford Press, 2015.

Kay Redfield Jamison, An Unquiet Mind. Vintage, 1996. (All Jamison page references are to this book.)

Kay Redfield Jamison, Fires in the Dark: Healing the Unquiet Mind.  Knopf, 2023.

Andrew Solomon, The Noonday Demon: An Atlas of Depression, with new material.  Scribner (2015)

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