In my latest for The New York Times, I revisit the topic of how antidepressants work. If they don’t “correct a chemical imbalance,” then what do they do?
Here’s a gift link for the article (the article is free to read with the gift link but unfortunately does require an email sign-up. If you are absolutely opposed to that but still would like to read the article, send me an email), and an excerpt below:
Let’s start with the grain of truth in the chemical imbalance story. Antidepressants such as S.S.R.I.s (selective serotonin reuptake inhibitors) and others do increase levels of certain brain chemicals called neurotransmitters. But as far as we can tell, they aren’t correcting a chemical deficiency. Instead, their beneficial effects seem to arise from a cascade of changes they set off within the nerve cells that then alter the activity of brain circuits and our thought patterns.
Depression and anxiety appear to involve a shift in how a person processes emotionally significant information. Neutral facial expressions take on a more disapproving and critical vibe. Negative memories are recalled more readily than positive ones. Rewards feel muted, while criticism feels overly painful. It is common for people with depression or anxiety to feel stuck in a persistent loop of negativity.
Researchers at the University of Oxford have shown that antidepressants shift this negative emotional information processing in a positive direction. This effect becomes evident fairly quickly after a person starts taking antidepressants — within days, sometimes after a single dose.
But this change in how emotional information is processed isn’t enough to lift people out of a state of depression or anxiety. What follows is typically a period during which people relearn how to see themselves and the world. Once they are no longer filtering everything through negative lenses, their brains can gradually accumulate more neutral or positive experiences of themselves and the world around them.
The environment of a medicated person plays a crucial role in this relearning. People with more social support and positive interpersonal relationships, including psychotherapy, tend to gain more from the medications.
Related to these changes in emotional processing is the idea, popularized by the psychiatrist Peter Kramer, that antidepressants reduce neuroticism, a personality disposition toward worry, negative emotions and stress sensitivity. In one clinical trial, patients on an S.S.R.I. called paroxetine showed substantial reductions in neuroticism that were not explained simply by improvement in depression.
Another way in which antidepressants may work involves the enhancement of neuroplasticity, or the brain’s ability to reorganize its structure and connections. Continued treatment with antidepressants may bolster brain chemicals and processes that promote neuroplasticity. (Psychedelics are thought to work as a treatment for depression and anxiety, in part, for a similar reason.) The hypothesis is that the drugs open a “window” of plasticity through which the brain has a renewed ability to change the way it is wired. Patients treated with antidepressants often feel more mentally malleable and better able to move away from unhelpful thinking patterns. Some researchers have proposed that we should think about antidepressants as relieving a kind of cognitive constipation.
[…]
All these explanations are not necessarily rivals, but better understood as complementary descriptions of processes unfolding at different levels in different people. A common theme among these hypotheses is that antidepressants alter the conditions under which people interact with the world and with their emotions. Antidepressants can make circumstances appear less threatening; they soften sensitivity to stress and loosen rigid patterns of thoughts, allowing people to escape from them. What many of these hypotheses suggest is that medication alone is not enough. Medication treatment needs to be complemented with the appropriate psychological and social changes.
Therapeutic Window #1: What if A.D.H.D. Isn’t About Attention at All? (gift link)
See also:
This part felt like an ah-ha moment for me:
"People with more social support and positive interpersonal relationships, including psychotherapy, tend to gain more from the medications."
As someone whose best experiences with anti-depressants have fit the "emotional blunting" story, I can see that it might have been a socially and emotionally impoverished life that caused the impact of the drug to be blunting rather than the start of some life-changingly positive emotional journey. Thinking back, the people I remember telling me that antidepressants "saved their life" or were otherwise super-positive have all been people who lived with loving romantic partners. I'm sure that's far from 100%, but it makes sense that antidepressants would work for some people who have love and support available but aren't responding to it due to the depression.
"The evidence for neuroplasticity is currently still up for debate. But the hypothesis that antidepressants alter how readily the brain learns from experience by facilitating neuroplasticity remains a leading candidate for why they work."
I do feel deeply doubtful about this "neuroplasticity" explanation. For instance, is it not "neuroplasticity" when the neurotic person tells a joke, sees that no one laughs, and in the future becomes anxious or socially avoidant whenever reminded of the topic of the joke, the people who didn't laugh, and all kinds of other stimuli only loosely related to the original situation? Negative emotional reactivity enhances learning of new threats. Without knowing the science, I suspect it's more like the antidepressants decrease the salience of signaling around negative memories/perceptions of threat or futility, and that frees up mental space to focus on other things, which can lead to a period of learning positive new behaviors and ways of seeing the world under the right circumstances.
But under the wrong circumstances, where there isn't much positive in the past or present to take the space of the down-regulated mental activity, or when the person has no alternate skills for taking advantage of their environment (for instance, no relationship skills that aren't based in negative emotions), the person just feels flat and dull and certainly does not get any better at learning.
"...Depression and anxiety appear to involve a shift in how a person processes emotionally significant information...". Whatever is salient , that is, whatever correlates to the salience network for longer than a few minutes, is an ideal physical definition of value-formation; not neurotransmitters.
I'm beginning to endorse the view that mental disorders, in their essence, are no more than misplaced (unobtainable) values and the pathological routines & rituals people erect in pursuit of those values. They are wish-fulfillment disorders.
All the complexity, comorbidity, severity, dynamisms, and so forth that psychiatry wants to use as a competing hypothesis against Freud are merely non-pathological features of the mind. That a person is "highly dynamic" or "highly rigid" in their presentation has nothing at all to do with mental disorder, causally speaking. The latter are merely features of a person's own becoming, not the mental disorder. As well, that a person is highly comorbid or complex, for example, is merely evidence of how many cognitive strategies they're able to deploy to chase said misplaced values. Were one to undergo mania every month, for example, this is merely because a misplaced value precedes their choosing to break away from their non-manic routines to go into this state, because mania produces creative states, and creative states are useful means of chasing unobtainable values.
Never in my life would I ever thought i'd agree with Freud.