Researchers have spent a significant amount of time trying to figure out the mechanisms that cause depression in an effort to develop preventative and treatment strategies for the mental condition. Over decades of intense research, three theories have emerged as the most plausible.
The monoamine theory posits that the depletion of key hormones such as serotonin, norepinephrine and/or dopamine was instrumental in the development of antidepressants. This theory stated that a chemical imbalance in the brain and nervous system was to blame for the development of depression.
More specifically, it said that a deficiency in monoamine transmitters was the primary cause of depression after animal experiments and clinical observations showed that a high blood pressure medication called reserpine that depleted neurotransmitters caused depression-like symptoms.
As such, researchers figured that they could alleviate depressive symptoms by taking medications designed to boost neurotransmitter levels; these substances were called antidepressants.
The theory has been criticized for decades because antidepressants often take weeks to cause a noticeable change in symptoms. In addition, only 40% to 60% of patients reporting a reduction in symptoms within six to eight weeks of beginning antidepressant therapy.
After zimelidine, the first SSRI in the world, proved to cause significant side effects, Prozac was adopted as the main antidepressant in several countries and gained immense popularity. It became the most-prescribed pharmaceutical drug in the United States only three years after its introduction and was the second most-prescribed drug globally four years after it was introduced.
The success of Prozac ensured that SSRIs would be the first line of defense against depression for the coming decades because it had proved that the monoamine theory had a basis.
However, current antidepressants, which are all monoaminergic, cause side effects such as anxiety, nausea, irritability, headaches, appetite changes, weight fluctuation, insomnia, diabetes and more.
With pharmaceutical companies operating under this theory, even as research has shown that antidepressant therapies aren’t completely safe and effective, the development of more efficient therapies has stalled.
The inflammation theory is another promising theory about the possible cause of depression. This theory states that increased levels of cytokines, which are signaling molecules tasked with activating inflammatory responses, result in elevated levels of anxiety and depression.
Inflammation may be a natural immune response against harmful stimuli, but it can harm the body if it occurs at elevated levels. Data has shown that antidepressants tend to be less effective in patients who have inflammation. In fact, antidepressants that stimulate serotonin production may actually encourage an inflammatory response by stimulating serotonin bound to serotonin receptors.
Regardless of which theory is the most correct, what patients see are alternative treatments that are effective and don’t come with a laundry list of side effects. Entities such as Field Trip Health Ltd. (OTC: FTHWF) (TSX: FTHW) are conducting drug-development programs to tap psychedelics to address this need.
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