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Selective Serotonin Reuptake Inhibitors: The good, The bad and The ugly: The role of serotonin.

What are Selective Serotonin Reuptake Inhibitors (SSRIs)?

Selective Serotonin Reuptake Inhibitors (SSRIs) are antidepressants. They fall under the class of drug that inhibits the uptake of serotonin with little to no effect on any other neurotransmitter, noradrenaline or any related proteins or enzymes. This effectively causes the concentration of serotonin to increase. The following are some of the most widely prescribed SSRIs

  1. Citalopram 

  2. Fluoxetine

  3. Fluvoxamine

  4. Paroxetine

  5. Escitalopram

  6. Sertraline

The exact biological mechanism of SSRIs (How SSRIs interact with the nerves to stop the uptake of serotonin) remains unknown. However, over time, they have proven to be effective in treating both depression and anxiety. They are usually first in line for treatment when drug therapy is considered for depression and anxiety.

What is serotonin?

5-hydroxytryptamine (5HT) commonly known as serotonin, is a hormone and neurotransmitter. Serotonin has multiple biological functions such as (but not limited to): bowel movements, blood clotting, nausea (to expel toxins it ingested) and sexual functions. I am limiting the discussion of the effects of serotonin on mood only, as discussing all of the functions of serotonin is beyond the scope of this blog. However, they will be covered briefly. Serotonin is made in the body using an essential amino acid called tryptophan (TRY). Since our bodies are not capable of producing TRY, we need to fulfil the need by external consumption of TRY.

The role of serotonin in Anxiety and Depressive disorders

The exact role or mechanism of serotonin in the treatment of depression and/or anxiety is unknown. However, due to its effectiveness, it is hypothesised that serotonin has a vital role in the regulation of our mood.

In 2014, a study on genetically engineered mice that could not produce serotonin in their brains naturally suggested that serotonin may not play a role in depression. The mice showed no signs of depression, even when placed under stress. However, in a different study, Sachs and colleagues suggested that psychosocial stress is enhanced during serotonin deficiency.

Much of the recent literature has suggested that serotonin may not be as crucial to emotions as previously hypothesised. In an editorial, Prof. Healy had pointed out that SSRIs have shown to be less effective than tricyclic antidepressants in the treatment of depression. 

Further investigations need to be made to clarify its role in mood regulation.

The Bad...

Since serotonin has other biological functions, there are known side-effects of it, such as (but not limited to) nausea, sweating, excessive thirst, weight gain or loss, diarrhoea, sexual dysfunction.

Another issue that arises is Serotonin Syndrome. Serotonin syndrome is a potentially life-threatening complication of SSRIs that may occur due to drug-drug interaction, self-poisoning (suicidality has been documented in young patients using SSRIs) or even due to regular therapeutic use of it.

If you believe that you may have depression or anxiety you can get help here.


  1. Angoa-Pérez, M., Kane, M. J., Briggs, D. I., Herrera-Mundo, N., Sykes, C. E., Francescutti, D. M., & Kuhn, D. M. (2014). Mice genetically depleted of brain serotonin do not display a depression-like behavioral phenotype. ACS chemical neuroscience, 5(10), 908-919.

  2. Boyer, E. W., & Shannon, M. (2005). The serotonin syndrome. New England Journal of Medicine, 352(11), 1112-1120.

  3. Healy, D. (2015). Serotonin and depression.

  4. Felman, A. (2017). Why stress happens and how to manage it. Medical News Today.

  5. Hyttel, J. (1994). Pharmacological characterization of selective serotonin reuptake inhibitors (SSRIs). International Clinical Psychopharmacology, 9(Suppl 1), 19-26.

  6. Nutt, D. J., Forshall, S., Bell, C., Rich, A., Sandford, J., Nash, J., & Argyropoulos, S. (1999). Mechanisms of action of selective serotonin reuptake inhibitors in the treatment of psychiatric disorders. European neuropsychopharmacology, 9, S81-S86.

  7. Sachs, B. D., Ni, J. R., & Caron, M. G. (2015). Brain 5-HT deficiency increases stress vulnerability and impairs antidepressant responses following psychosocial stress. Proceedings of the National Academy of Sciences, 112(8), 2557-2562.

  8. Zisook, S., Trivedi, M. H., Warden, D., Lebowitz, B., Thase, M. E., Stewart, J. W., ... & Rush, A. J. (2009). Clinical correlates of the worsening or emergence of suicidal ideation during SSRI treatment of depression: an examination of citalopram in the STAR⁎ D study. Journal of affective disorders, 117(1-2), 63-73.

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