Is the Link Between Serotonin and Depression a Myth?


zoloft adDo you remember the old Zoloft (Sertraline) ad where the sad egg no longer chases the birdy, and whenever he moves, the thick cloud above follows him? Pfizer did a masterful job of taking a very complex phenomenon and simplifying it down to a concept that two-year-olds can understand. In fact, the visual props made such an impact on my husband that he continues to ask me, years after the original commercial, if I am a “sad egg” whenever he senses that I’m experiencing symptoms.

In the late 1980s and 90s, Pfizer wasn’t alone in dumbing down depression to a simple “chemical imbalance,” a shortage of neurotransmitters (messengers between neurons) like serotonin that can be replenished with a class of drugs called serotonin reuptake inhibitors (SSRIs).

According to a report by the National Center for Health Statistics, the rate of antidepressant use in this country among teens and adults increased by almost 400 percent between 1988-1994 and 2005-2008. Antidepressants were the third most common prescription drug taken by Americans of all ages in 2005-2008 and the most frequently used by persons ages 18-44 years. About one in 10 Americans aged 12 and over takes antidepressants.

But what if the explanation that led to the popularity of SSRIs isn’t true?

In his BMJ editorial, “Serotonin and Depression: The Marketing of a Myth,” professor of psychiatry David Healy explains how SSRIs gained their popularity. They essentially took over for tranquilizers and benzodiazepines in the late 1980s, since concern was emerging about the dependence of those drugs. Healy writes:

“Drug companies marketed SSRIs for depression, even though they were weaker than older tricyclic antidepressants, and sold the idea that depression was the deeper illness behind the superficial manifestation of anxiety. This approach was an astonishing success, central to which was the notion that SSRIs restored serotonin levels to normal, a notion that later transmuted into the idea that they remedied a chemical imbalance. The tricyclics did not have a comparable narrative.”

Healy goes on to explain that there was no correlation between serotonin reuptake inhibiting potency and antidepressant efficacy. No one knew, he says, if SSRIs really raised serotonin levels. However, the story about low serotonin levels served both doctors and patients because it was an easy one to communicate and underscored the biological reason for the distress, reassuring a person that it is not a weakness.

All of this is rather confusing to me, since I have taken an SSRI for over 20 years. For the first 10 years, it worked great, and saved me from a suicidal depression in my 20s. However, since my mega-breakdown in my 30s, I have started to research the causes for depression, and I realize mood disorders are far more complicated than an egg chasing a bird.

“It’s true that depression is not a serotonin deficiency,” Peter J. Kramer, M.D. told me this morning in an interview, “but it’s also true that serotonergic drugs allow for recovery from depression, and sometimes they seem to reverse it directly.” Kramer is Clinical Professor of Psychiatry and Human Behavior at Brown University and the bestselling author of six books, including “Listening to Prozac.”

I also spoke with Ron Pies, M.D., Professor of Psychiatry at SUNY Upstate Medical University and author of “Psychiatry on the Edge.”

“There is little question that the role of serotonin in depression was over-emphasized and over-marketed in the 1990s,” Pies explained to me, “though most psychopharmacologists understood that the neurobiology of depression was much more complicated. Indeed, the term ‘SSRI’ is itself a misnomer, since some of these agents also affect other brain chemicals (e.g., sertraline has mild effects on dopamine). None of this, however, should be used in service of the equally mythological claim that ‘antidepressants don’t work’ or are ‘no better than a sugar pill.’ This is demonstrably false, at least with respect to moderate-to-severe depression.”

Pies has argued elsewhere that most academic psychiatrists and researchers never bought into the “chemical imbalance” notion to begin with. It was promoted mostly by pharmaceutical companies. However, that is a separate issue as to whether or not they work.

“Medications often arise that are known to ‘work’, even though their precise mechanism of action remains unknown for decades–aspirin is one example!” he explained. “Debunking or diminishing the role of serotonin in depression in no sense refutes the data that antidepressants, including those acting on both serotonin and norepinephrine (SNRIs) result in clinically important benefits for accurately diagnosed persons with major depression. Probably, these medications work better when combined with some form of psychotherapy, which is often the preferred ‘first line’ treatment for milder cases of major depression.”

I do agree with Healy that with the success of SSRIs, some very effective and less costly treatments were marginalized. It wasn’t until I landed in the Mood Disorders Clinic at Johns Hopkins Medical Center that I tried a tricyclic (nortriptyline) and a mood stabilizer (lithium) that got me well and kept me well for a few years. At that point, I had tried almost every kind of SSRI.

I also agree that we need to be more sophisticated in our explanation of depression, and we need to explore the connection between mood disorders and different biological systems, such as digestion that I blogged about recently.

But I hope his piece won’t discourage someone who could very well benefit from an SSRI after trying psychotherapy and a few things (better diet, meditation, exercise, yoga).

Because SSRIs can be agents of hope.

Join Project Beyond Blue, the new depression community.

Originally published on Sanity Break.

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Therese Borchard
I am a writer and chaplain trying to live a simple life in Annapolis, Maryland.

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7 Responses
  1. Thanks for presenting both sides so clearly. I like seeing bad science debunked or at least clarified. But the “antidepressants don’t really work” claim has become very common lately, and that’s just as wrong as the “serotonin imbalance” marketing hype.

    I get that “antidepressants work, but we don’t understand exactly why, and you still have to do all these other things” is a weak marketing angle, but at least it’s honest.

  2. John G Diehl


    Excellent article! It’s a complex illness, both as to treatments and causes. Thank you for continuing to address various myths, nuances, alternative treatments, biological and physiological connections, and for citing many credible references and expert opinions (as you always do). Seems like treatment is still trial and error, like alchemy. I understand there are some tests, e.g. DNA swab analysis and blood tests, but the results still seem primarily tied to the trial and error method of pharmacological treatment.

    Thank you for what you do, and for continuing to shed light and bring hope to so many.

  3. Great post about depression. I think it is important to reach out and seek help wether if you are experiencing severe suicidal feelings or mild depression. Also, its important to seek for non-pharmacological treatments, as the “happiness pills” are only temporary solutions to the problem.

    People need to go to the root of their depression and overcome it from there, not cut of one branch of the problem (as you do with drugs) because the problem will eventually grow out again.

    Wish you the best of luck!