Mya Care Blogger 04 Aug 2022

Medically Reviewed by Dr. Sony Sherpa (MBBS) - August 04, 2022

Depression, which can be defined as persistent low mood, is thought to be due to a decrease in the serotonin level in the synaptic cleft. A synaptic cleft is a space between neurons where information from one neuron is sent to the other through neurotransmitters, which relay the nerve impulse. Serotonin is considered one of the neurotransmitters associated with depression. So, antidepressant medicines that increase the level of serotonin in the synapse are frequently used to treat depression.

However, a recent umbrella review propounded that there is no clear evidence to suggest that low serotonin is the cause of depression, raising a debate on the high prescription rate of antidepressants. The review attempted to include all the relevant studies in the research on serotonin and depression. As a result, 17 different studies involving thousands of subjects were analyzed to come to this conclusion.

Furthermore, the study cited the high prescription rate of antidepressants based on unconvincing evidence. One in every six adults and 2% of teenagers have been prescribed antidepressants in England, similar to the worldwide scenario.

Association Between Serotonin Deficiency and Depression

There is a general perception that depression is due to serotonin deficiency and that antidepressants act as a supplement. However, the umbrella review showed no direct correlation between lower plasma serotonin levels and depression. Furthermore, no significant difference was found in the serotonin level and its breakdown products in the plasma and brain fluid between the general population and people suffering from depression.

The authors also looked at research on serotonin receptors and the serotonin transporter, the protein targeted by most antidepressants. They found weak and inconsistent evidence suggesting higher levels of serotonin activity in people with depression. According to the researchers, the findings are most likely linked to antidepressant use among people diagnosed with depression.

Furthermore, the review also discovered that studies in which serotonin levels in healthy individuals were lowered artificially through a particular diet did not increase their risk of developing depression.

Additionally, according to the review, no differences in serotonin-related genes between depressed individuals and healthy participants were discovered in genetic studies. However, a recently released meta-analysis suggested that people who carry a particular serotonin-related gene variant are more likely to experience depression in response to a traumatic event in their lives. However, this was true only for chronic stress. So, it suggests a complex interaction of genes, environment, and time factors in cases of depression. This meta-analysis was not included in the “umbrella review," as the meta-analysis was published recently.

Thus, these findings conclude that there is no clear evidence that depression is related to low serotonin levels. Therefore, the study suggested that people should be made aware of this observation and that the prescription of antidepressants should not be promoted as a serotonin-increasing therapy. This is particularly important because 85-90 % of the public believes that depression is due to low serotonin levels or a chemical imbalance.

However, there are studies suggesting the effectiveness of antidepressants in treating depression. Therefore, another group of experts questioned the findings of this new study and advised people not to stop their antidepressants.

The study's authors have clarified this by not denying the efficacy of antidepressants for depression but questioning how antidepressants work. They have also pointed out the inefficacy of the drug for a large group of people for whom antidepressants did not work. Additionally, they also found that long-term antidepressant use reduces serotonin concentration. According to the researchers, this may imply that the short-term serotonin increase caused by some antidepressants could result in compensatory changes in the brain that have a long-term opposite effect.

The study suggests that people should be provided with accurate information about the disease and should not be misinformed about depression and the use of antidepressants based on unproven claims. Instead, people must be enabled to make an informed decision about taking antidepressants.

Although the study did not examine the effectiveness of antidepressants, the authors encourage more research and guidance into therapies that might instead concentrate on helping people manage traumatic or stressful life events and addressing underlying contributors such as poverty, stress, and loneliness. These therapies include psychotherapy alongside other practices like exercise or mindfulness.

A group of scientists and professional bodies have argued that the study has oversimplified the complex relationship between chemical and neurological associations and depression by completely ruling out the role of serotonin. However, they also do not deny that the association is inconclusive and that further study is required. Furthermore, it is regarded that a better treatment approach for depression is needed.

The Takeaway

In conclusion, the study raised a debate regarding the role of serotonin in depression and questioned the use of antidepressants. However, the study also suggests not to stop antidepressant medication on your own and instead consult your doctor and follow their advice.

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  • Moncrieff, J., Cooper, R. E., Stockmann, T., Amendola, S., Hengartner, M. P., & Horowitz, M. A. (2022). The serotonin theory of depression: a systematic umbrella review of the evidence. Molecular Psychiatry, 1-14.
  • Cowen, P. J., & Browning, M. (2015). What has serotonin to do with depression?. World Psychiatry, 14(2), 158.
  • Chu, A., & Wadhwa, R. (2022). Selective serotonin reuptake inhibitors. In StatPearls [Internet]. StatPearls Publishing.
  • Delli Colli, C., Borgi, M., Poggini, S., Chiarotti, F., Cirulli, F., Penninx, B. W., ... & Branchi, I. (2022). Time moderates the interplay between 5-HTTLPR and stress on depression risk: gene x environment interaction as a dynamic process. Translational psychiatry, 12(1), 1-12.
  • Cipriani, A., Furukawa, T. A., Salanti, G., Chaimani, A., Atkinson, L. Z., Ogawa, Y., ... & Geddes, J. R. (2018). Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Focus, 16(4), 420-429.