Neurotransmitters can't tell the whole story,
no matter what "serotonin culture" says.
By Grace Huckins July 1, 2019
Grace Huckins is
a Ph.D. student in neuroscience and philosophy at Stanford University. She
holds two master’s degrees, in neuroscience and gender studies, which she
obtained from the University of Oxford with the support of a Rhodes
Scholarship. She currently writes and produces a podcast for NeuWrite West, an
online outlet dedicated to the communication of neuroscience, by
neuroscientists, to a public audience. In the past, she has written extensively
on arts and culture for The Harvard Crimson. She lives in San Francisco,
California.
Antidepressants
aren't a perfect solution to depression. So why do we act like they are?
On the internet, in
newspapers, and in casual conversation, the brain can sound like an amusement
park: reward centers “light up,” dopamine “floods” our system, we experience an
“adrenaline rush.” In this simple world, depression is no longer a mysterious,
devastating specter: it’s nothing more than a shortage of serotonin, the
brain’s “happy chemical.” Unfortunately for those who suffer from depression,
however, the truth is not nearly as straightforward as the internet might lead
us to believe.
Serotonin's association
with happiness and depression recovery is so well known that the molecule has
become lucrative. On Etsy, one may browse nearly 2,000 serotonin-themed
necklaces, earrings, and trinkets. In loving homage to TV chef extraordinaire
Ina Garten, Reddit user /u/annybananny coined a
slogan that has since circulated widely on social media: Much
like tomato sauce or pie crust, "If you can't make your own
neurotransmitters, store-bought is fine." The motto has since been plagiarized by dozens of opportunists looking
to make a quick buck.
Undoubtedly, there's value
in a phrase that implicitly equates Prozac with artificial insulin. Just as
diabetes is no more than the body's inability to produce its own insulin, so
too is depression a straightforward, explicable physical ailment. Dozens of studies
have established that stigma worsens
the severity of mental illness symptoms, so the belief that mental
illness and physical illness are really no different might literally alleviate
one's depression.
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There's one glaring
problem, however: there's no evidence that a lack of serotonin causes
depression. While this theory, termed the "monoamine hypothesis" of
depression, has remained popular since it was first proposed in the
1960s, by the 1990s various strains of evidence had
established that it was at best a gross oversimplification. And the idea that
depression treatment is as simple as augmenting your meager supply of
neurotransmitters might actually be harmful.
Serotonin
and SSRIs: A deceptively simple story
To the credit of public
science (or, perhaps, the pharmaceutical
industry), the basic contours of "serotonin culture" hold
water. The jewelry and wall decorations available online accurately represent
the structure of serotonin, a small, organic molecule that the human body makes
naturally from L-tryptophan, an amino acid found in numerous foods. It is one
of many neurotransmitters, molecules that neurons use to communicate with one
another over the gaps between them, called synapses. When one neuron releases
serotonin into a synapse, the molecules drift across to the subsequent neuron,
in which they can provoke a variety of responses.
Serotonin also almost
certainly plays a role in most pharmacological treatment of depression.
Lexapro, Prozac, and Zoloft are all selective serotonin reuptake inhibitors
(SSRIs), which means they prevent neurons from clearing serotonin out of their
synapses. The serotonin then lingers in the synapse, where it can exert more of
an effect on the neuron that receives it. SSRIs aren’t themselves serotonin
pills—they don’t contain neurotransmitters—but they do act to increase the
influence of serotonin in the brain.
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The efficacy of SSRIs and
of their precursors, monoamine oxidase (MAO) inhibitors, motivates serotonin
theory. In fact, the monoamine hypothesis first arose when physicians discovered by chance that MAO
inhibitors, which were used to treat tuberculosis, also had a positive effect
on patients' moods. If drugs that increase serotonin in the synapses
can alleviate the symptoms of depression, it stands to reason that those
symptoms could be caused by a lack of serotonin.
Serotonin
theory was a great hypothesis—but it didn't hold up under scrutiny
Even today, the relief that
antidepressants provide for the 13% of Americans who take them remains
the strongest evidence in favor of serotonin theory. But even that evidence is
not bulletproof; upon examining the data more closely, the walls of serotonin
theory quickly begin to crumble.
The first major hole in
serotonin theory is the timeline of SSRI effects. Whereas a depressed patient
who begins SSRI treatment will have increased serotonin levels in their
synapses within
hours, SSRIs take
four to six weeks to exert a measurable effect on symptoms. If
depression is simply a lack of serotonin, one would expect such a therapy to
provide much quicker results.
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This is not to say that
serotonin is meaningless. Given enough time, SSRIs absolutely
do have a measurable impact on depression symptoms when
compared to placebo. Unfortunately, and quite worryingly for a culture that
views SSRIs as an emotional panacea, these effects are not as dramatic as one
might hope. When a group of researchers obtained antidepressant drug trial data
from the FDA under the Freedom of Information Act, they discovered that
placebos were 80% as
effective as antidepressants.
Here is where our serotonin
culture gets particularly dicey: A depressed individual who begins SSRI
treatment might expect that, with their serotonin levels returned to normal,
their illness will at last be cured. But there is a 40% chance that
the first SSRI they try won't work for them at all. The search for the right
treatment plan can be a lengthy and trying process, and it carries its own
significant risks: there is evidence that SSRIs can actually increase suicidal
ideation, particularly in younger patients.
Effective
depression treatment is much more than a matter of serotonin
Even though serotonin
theory may reduce the stigma surrounding depression, we need to start telling a
more complex story if we want to help patients find effective treatment.
Serotonin and depression are by no means unrelated, but scientists are still
trying to work out how exactly that link works, and there is no simple or
guaranteed cure for depression. Successful SSRI treatment can take months of
trial and error, and those uncertain months are critical to finding the best
possible pharmacological treatment.
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Equally essential are the
various non-pharmacological treatment options available to depressed patients.
Talk therapies like CBT (cognitive behavioral therapy) are extremely effective; a significant body of work has
shown that CBT works just as well as antidepressants, on average, and may even
more effectively prevent remission. When used together, CBT and antidepressants are
more effective than either is alone.
And one of the most
successful treatments for mild and moderate depression is free, widely
accessible, and multipurpose: exercise.
Other pharmacological agents may even work better than SSRIs. Ketamine can
almost immediately alleviate suicidal thoughts, and psychedelic
drugs are showing promise as a potential treatment. Ignoring
the full spectrum of treatment options in favor of a myopic focus on SSRIs
could have a devastating human cost.
Just as physicians in the
1950s prescribed MAO inhibitors before they had formulated serotonin theory,
today our portfolio of depression treatments far outpaces our understanding of
the underlying causes and mechanisms. Though it may be decades until we have a
working theory of depression that accommodates the current evidence, in the
meantime, we can continue working on the ultimate goal of all such research:
returning joy and hope to those who may have despaired of ever experiencing
those emotions again.
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