Antidepressants are one of the most popular drugs in the US. According to the CDC, during 2015–2018, 13.2% of adults used antidepressants.
Prozac (fluoxetine), Paxil (Paroxetine), Celexa (Citalopram), and Zoloft (Sertraline) are popular Selective Serotonin Reuptake Inhibitors (SSRI) used to treat depression.
The idea behind using the SSRIs came from the serotonin theory of depression, which says that people with depression have low serotonin levels in their brains.
The drug industry wants people to believe that SSRIs increase serotonin levels and, therefore, can treat depression.
But is it true?
Nature published in July 2022 a review of 17 studies that looked at genetics, receptors, and the relationship between serotonin levels and depression.[1]
To better understand the detail of the study, I modified the figure below from Neurowiki to show how serotonin is used between nerve cells.
The Mechanism of Serotonin
Nerves carry electrical signals. That electrical signal is changed to a chemical messenger or neurotransmitters like serotonin in the gap between two nerve cells: the presynaptic neuron and the post-synaptic cell.
- (1) Serotonin or 5-HT comes from L-tryptophan
- 5-HT goes to the end of the presynaptic neuron (2) and is released in the synaptic cleft, (3) which is the space between the presynaptic and post-synaptic neuron
- Serotonin transporters (SERT) carry serotonin to bind to the 5-HT receptor at the post-synaptic neuron (4) and get stimulated.
- The serotonin gets released back to the synaptic cleft (5) and reuptake again by the presynaptic cleft (6)
In the serotonergic theory, there is not enough serotonin; therefore, the post-synaptic neuron does not get stimulated, and depression symptoms occur.
SSRIs are supposed to block serotonin reuptake (7), increase the serotonin available for the post-synaptic neuron, and relieve depression symptoms.
Here are their findings.
There is no correlation between the low levels of serotonin with the symptoms of depression.
Our comprehensive review of the major strands of research on serotonin shows there is no convincing evidence that depression is associated with, or caused by, lower serotonin concentrations or activity.
Low levels of tryptophan, the precursor of serotonin, do not produce depression symptoms.
Most studies found no evidence of reduced serotonin activity in people with depression compared to people without, and methods to reduce serotonin availability using tryptophan depletion do not consistently lower mood in volunteers.
There is no association between the SERT gene variations that produce the serotonin transporters and depression.
High quality, well-powered genetic studies effectively exclude an association between genotypes related to the serotonin system and depression, including a proposed interaction with stress.
There is inadequate evidence that the activity of the serotonin receptors and depression are related.
Weak evidence from some studies of serotonin 5-HT1A receptors and levels of SERT points towards a possible association between increased serotonin activity and depression.
However, these results are likely to be influenced by prior use of antidepressants and its effects on the serotonin system.
Overall the authors conclude,
The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations.
What is worrisome is that the SSRIs may lower serotonin instead.
Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration.
A Clinical Meta-analysis
The findings align with a 2017 meta-analysis of 131 randomized placebo-controlled trials enrolling 27,422 participants.[2] The first study did not include this meta-analysis.
Jakobsen et al. found that although studies show that SSRIs affect depression symptoms, the results are not convincing because of the high risk of bias.[2]
SSRIs might have statistically significant effects on depressive symptoms, but all trials were at high risk of bias and the clinical significance seems questionable.
Sources of bias
The absence of random sequence generation, allocation concealment, blinding participants and personnel, incomplete outcome data, selective reporting, and for-profit bias indicate bias.
SSRIs significantly increase the risk of both serious and non-serious adverse events.
The potential small beneficial effects seem to be outweighed by harmful effects.
Adverse events with SSRIs
The adverse events are suicide attempts, bowel obstruction, nausea, arrhythmia, respiratory arrest, retinal detachment, chest pain, worsening of depression, atrial fibrillation, femur fracture, coronary artery occlusion, pneumonia, confusional state, anxiety/agitation/racing thoughts, syncope, ankle fracture, viral gastroenteritis, miscarriage, non-accidental overdose, suicide, intestinal fistula, diabetes and
hypothyroidism, fibrocystic disease, ovarian cysts, peptic ulcer bleeding, spinal surgery, hypomanic episode with suicidal tendencies, alcoholism, neoplasm, acute
pyelonephritis, thrombophlebitis, ectopic pregnancy, polycystic granuloma, basal cell carcinomas, myxoid mitral valve, and many others.
No difference between SSRIs
The authors also compared the different SSRIs and found no significant differences, indicating the effects (or lack of effects) of the various SSRIs are similar.
However, the authors mentioned that “certain severely depressed patients might benefit from SSRIs despite no evidence backing this hypothesis.”
With the three-fold increase in depression symptoms during the pandemic lockdowns, there is a possibility that SSRS use may be higher now.
Allied Market Research expects the antidepressant market to reach $15.98 billion by 2023.
That is billions of dollars spent on drugs, still lacking convincing scientific evidence.
Truth heals. Lies kill. Don’t Get Sick!
Stay current by subscribing. Feel free to share and like. Please consider donating to show your support if you find value in this website.
References:
- Moncrieff, J., Cooper, R.E., Stockmann, T. et al. The serotonin theory of depression: a systematic umbrella review of the evidence. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-022-01661-0
- Jakobsen JC et al. Selective serotonin reuptake inhibitors versus placebo in patients with major depressive disorder. A systematic review with meta-analysis and Trial Sequential Analysis. BMC Psychiatry. 2017 Feb 8;17(1):58. doi: 10.1186/s12888-016-1173-2. Erratum in: BMC Psychiatry. 2017 May 3;17 (1):162. PMID: 28178949; PMCID: PMC5299662.
© 2018 – 2022 Asclepiades Medicine, L.L.C. All Rights Reserved
DrJesseSantiano.com does not provide medical advice, diagnosis, or treatment