Scientists may not know why, but antidepressants work


Aantidepressants work. Antidepressants don’t work. Which is it? Let’s ask two academic psychiatrists who believe they are doing it, although scientists don’t know exactly why.

… Psychiatrists have never explained clinical depression solely in terms of reduced serotonin or any particular neurotransmitter.

Here we are right in the middle of the question, “Do antidepressants work?” donnybrook.


Two weeks ago I posted “Serotonin and Depression: Is There Really a Link?.”

It is a discussion of a recent University College London (UCL) press release entitled “No Evidence that Depression is Caused by Low Serotonin Finds Comprehensive Review.”

This comprehensive review was conducted by a team of UCL researchers and published in Molecular Psychiatry.


No serotonin, no chemical imbalance

The essence of the team is summed up in the title of the release. And we can add to her claim that depression is unlikely to be caused by a chemical imbalance.

That’s right, so why bother with antidepressants?


I have not questioned the accuracy of the data used in the review. However, I felt a “Agenda-driven bias” and “unyielding bite” that made me uneasy.

For the record, two of the team members published a follow-up article attacking antidepressants more directly.

First of all, this is a long article. But it has to be, given the abundance of interesting and worth knowing information.


So make yourself comfortable, take breaks, read it over a few days, whatever – you don’t want to miss this.

Serotonin or not, antidepressants work

Apparently I wasn’t the only one uncomfortable with the review.

Came across an article in the Psychiatric Times entitled “Serotonin or Not, Antidepressants Work” written by academic psychiatrists and psychopharmacologists Ronald W. Pies, MD, and George Dawson, MD.


The byline: “The latest claim that antidepressants don’t work: disproved.”

dr Pies and Dr. Dawson get straight to the point…

In our view, the gullible, media-driven narrative generated by the review and follow-up article amounts to old-fashioned rhetoric — and the review itself is little more than old wine in new bottles.

In addition, we find at least 7 serious issues with the review’s claims, each of which undermines the review’s thesis, as we will detail.

We will deal with these “serious problems”. I had to do some serious compression and editing. The doctors were on a mission.

7 serious problems with the review’s claims

  1. “Psychiatry” has never proposed a theory of depression that claims it is caused by one or more neurotransmitters. dr Dawson performed undertook a detailed review and found no evidence of a “chemical imbalance theory” of mental illness in any standard psychopharmacology textbook or peer-reviewed literature for the last 30 years.
  2. Psychiatrists have known for decades that the cause of depression and other mood disorders cannot be explained in terms of a single neurotransmitter. Additionally, psychiatrists and neuroscientists have proposed at least 17 other hypotheses about depression between 1990 and 2010, with eight additional ideas since then.
  3. The overview does not capture the complexity of serotonergic (serotonin-related) systems and signaling in the brain. Recent work in this area shows that although serotonin systems are now much better characterized, additional work needs to be done. The review’s claim that psychiatric research on serotonin has not yielded any useful information – and that this entire area of ​​research should be brought to a conclusion – does not accurately reflect the current scientific research program.
  4. The information in the review was nothing new to psychiatrists. At least four studies of the 5-HT (serotonin) hypothesis have found inconclusive or conflicting evidence. The most recent review (2017) concluded that additional evidence was needed to support the model and remove inconsistencies. These authors also proposed several new 5-HT receptor-based hypotheses.
  5. The brain contains about 50 to 100 neurotransmitters. Hypotheses about depression go well beyond serotonin – in fact, well beyond biogenic amines (e.g., the monoamines). The review focuses solely on serotonin and does not address other small molecule or neuropeptide neurotransmitters (e.g. galanin) that may play a role in antidepressant effects. Additionally, the review does not address potent non-serotonergic antidepressants such as bupropion (Wellbutrin) or antidepressants such as vortioxetine (Trintellix), which have very complex serotonergic effects.
  6. In the field of drug development, there is a lively debate about whether a specific mechanism of action and/or a specific target molecule is required for the approval of a drug. dr Dawson recently reviewed the package inserts of medications approved by the FDA as disease-modifying drugs for multiple sclerosis. Eighteen drugs have been approved since 1993, but the mechanism of action for 17 of the 18 drugs is listed as unknown.
  7. The techniques described in the review were not designed to determine the effectiveness of antidepressants, which is determined by randomized controlled clinical trials. Therefore, no conclusions can be drawn from the review regarding the effectiveness of antidepressants or the “good versus harm” associated with antidepressant treatment.
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I told you they’re on a mission.

Clinical approach to depression

antidepressants work

“Okay, I understand both sides. Now I can work on an informed decision.”

Pies and Dawson weren’t done yet.

They go on to say that in response to the UCL review, several neuroscientists and researchers have suggested that serotonin’s role in mood disorders is not a proven science.

It may well play a role in some types of depression.

you quote Psychiatrist and researcher Michael Bloomfield, MD…

I don’t think I’ve met any serious scientists or psychiatrists who think all that [cases] of depression are caused by a simple chemical imbalance in serotonin. What remains possible is that in some people with certain types of depression… changes in the serotonin system may contribute to their symptoms. The problem with the review is that… depression has been lumped together as if it were a single disorder that makes no biological sense.

Pies and Dawson express their primary concern: The review in no way calls into question the overall safety and efficacy of serotonergic antidepressants in the acute treatment of moderate to severe major depression.

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However, we believe that antidepressant treatment should be administered conservatively, closely monitored, and viewed only as a single component of a comprehensive, biopsychosocial approach to the management of depression, which generally involves talk therapy.

Therefore, patients should be educated about all three components of mood disorders: biological, psychological, and sociocultural.

Finally, the benefit-risk discussion regarding antidepressants (and other biological treatments in psychiatry) should be approached in the same way that the physician would approach any other serious medical intervention.

dr Pies and Dr. Dawson close

dr Pies and Dr. Dawson conclude her article by citing depression as a complex, heterogeneous disorder with biological, psychological, and sociocultural determinants and risk factors.

They further state that few, if any, US psychopharmacologists and academic psychiatrists have ever advocated a comprehensive theory of the chemical imbalance of mood disorders.

Historically, psychiatrists have never explained clinical depression solely in terms of reduced serotonin or any particular neurotransmitter.

Finally—and perhaps most importantly—Pies and Dawson hope that scrutiny or the fact that the mechanism of action of SSRIs is complex and not fully understood will not discourage patients and clinicians from using antidepressants.

An informed decision

antidepressants work. Antidepressants don’t work. Which is it? Well, you got a full dose of the “you do” side. Two weeks ago you got the “not”.

And now you can work on making an informed decision.

Take the time to read “Serotonin or Not, Antidepressants Work” in the Psychiatric Times. You will find a lot of information and tables that I could not possibly include.

And be sure to read the “Don’t” position “Serotonin and Depression: Is There Really a Relationship?”

More information and inspiration articles on Chipur Mood and Anxiety Disorders? Please


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