Depression and the low serotonin myth

black_white_sad_face.jpgOpen-access medical journal PLoS Medicine has published an essay on the popular but poorly supported claim that depression is ’caused’ by low serotonin and that some antidepressant drugs correct this ‘chemical imbalance’.

The essay particularly focuses on a class of antidepressant drugs called ‘selective serotonin re-uptake inhibitors‘ or SSRIs, that increases the amount of the neurotransmitter serotonin available to neurons, by preventing its re-absorption after normal use. Prozac is, perhaps, the most famous example.

The authors contrast the claims of SSRI adverts, that usually claim that depression is caused by a serotonin imbalance in the brain, and the scientific research, that reports little evidence for this link.

As previously reported on Mind Hacks, recent reviews of the neuroscience literature suggest that this view is oversimplified at best.

One of the most striking examples of this is the antidepressant Tianeptine. Tianeptine actually increases decreases serotonin levels, and yet is still an effective treatment for depression.

Antidepressant medication has been under the spotlight of late, as concerns about safety have been highlighted, and, controversially, two researchers recently questioned the effectiveness of antidepressant drugs outright.

This opinion is not mainstream, however, as the majority of psychiatrists and researchers accept published research that suggests that SSRIs are helpful in treating depression.

Link to “Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature”.
Link to write-up from
Link to ‘Is depression a brain disease?’


  1. cogneuroguy
    Posted November 10, 2005 at 5:40 pm | Permalink

    I think you meant to write, “Tianeptine actually DEcreases serotonin levels, yet still is an effective antidepressant.”

  2. colin
    Posted November 10, 2005 at 5:42 pm | Permalink

    I think you meant to write that Tianeptine “decreases” serotonin levels. However this is a bit of a oversimplification in it’s own right as what it is actually doing is increasing the reuptake. While this does of course more quickly remove serotonin from the synapse, this action potentially makes serotonin more ready for use again by the neuron. Additionally, there is “No data is available regarding effects of the drug on postsynaptic receptors.” Thus it is relatively uncertian how this drug works as well.
    As a result, we are left with a big mystery as to the actual acting mechanisms of these drugs. It’s not just a shortage of serotonin since if that were the case than SSRIs should have an immediate effect not the typical several week waiting period. Studies do show that they work however so something is happening. Possibly it’s caused by neuron growth in the hippocampus? This reason would take account for the time delay.

  3. Vaughan
    Posted November 10, 2005 at 5:48 pm | Permalink

    Hi Colin,
    You’re quite right. I was thrown by the fact that it is a serotonin reuptake *enhancer*. Although from checking PubMed it does increase the level of free serotonin. Thanks for the correction!

  4. Posted November 10, 2005 at 7:22 pm | Permalink

    Further reading on tianeptine – an interesting compound by all accounts. It seems although it initially decreases serotonin, longer term treatment tends to increase it, at least in this 1993 study
    I presume there’s more detail in this 2005 Molecular Psychiatry article, although I don’t have access to it unfortunately:

  5. colin
    Posted November 10, 2005 at 9:59 pm | Permalink

    Those abstracts are pretty interesting (wish I too had access to the full pub). They seem to corroborate my initial suspicion that Tianeptine actually indirectly allows for more serotonin to be released because it allows the neuron to more effectively reuptake and reuse use the serotonin (instead of just leaving it in the synapse for MOAs sweep up).
    If this is how they work then Tianeptine might be a “better” drug than the SSRIs, as Tianeptine probably leads to less potential of serotonin depletion.
    To add more confusion to it all, Tianeptine seems to affect the Norepinephrine system too by increasing NE in certian areas:

  6. g
    Posted December 31, 2005 at 2:33 pm | Permalink

    does anyone know if Stablon is approved for prescription in the UK?

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