Time to Close the Curtain on the Serotonin Show?

Jerry Kennard Health Pro
  • Serotonin as a cause of depression has not only had its moment, it has overstayed its welcome. In the form of a pill aimed at correcting an imbalance, it arrived in the 1980s and was welcomed with open arms. In fact it took the world by storm. Depression, we were informed, was the result of a chemical deficiency and the culprit was serotonin. Fluoxetine (Prozac) was an overnight success. It shot to the top as the number one antidepressant and spawned the development of other so-called selective serotonin reuptake inhibitors (SSRIs).


    In calmer moments it quickly became clear that the SSRIs weren’t actually more effective than older classes of antidepressants, but they did tick boxes in terms of their comparative lack of side effects. Even so, despite evidence that the clinical effectiveness of SSRIs has never been strong, their popularity hasn’t diminished.

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    Somewhere along the way a belief has taken hold that depression is caused by a lack of serotonin. If this were true all we’d need to do was increase it and our problems would be solved. This isn’t the case. Put bluntly serotonin may have a role in mood, but its absence doesn’t cause depression and its elevation doesn’t necessarily alleviate it.


    A bold claim – where’s the evidence? It occurred to me it was time to revisit the serotonin issue after reading a research review from the American Chemical Society journal Chemical Neuroscience (August, 2014). The thrust of the findings was that mice bred with an inability to produce serotonin in their brain showed no sign of depressive symptoms. Moreover, when put under stress, the little creatures reacted in exactly the same fashion as normal mice.


    The results of such an investigation are interesting but there are other dots in the puzzle just calling out to be joined. For example, the fact that around 60 – 70 percent of patients on SSRIs continue to feel depressed, can’t be ignored. The fact that no clinician or clinical researcher can tell us the cause of depression can’t be ignored. The fact that not all antidepressants have an effect on serotonin but appear no less effective, can’t be ignored. The fact that talk-therapies can be as or more effective than antidepressants, can’t be ignored.


    Studies looking for low serotonin levels in depressed people are generally inconclusive. But we also can’t ignore the fact that a proportion of people do seem to respond to SSRIs. Leaving aside the placebo effect, there are at least a couple of possible explanations for this. The first and most obvious is that these particular people do indeed respond to an increase in serotonin (although why that should take up to six weeks remains a puzzle). A second explanation is that filling up on SSRIs is having other effects.


    In my next Sharepost, I’ll be considering these other possibilities and speculating on the direction clinical science could be heading in its attempts to treat depression more effectively.

Published On: September 26, 2014