The evolution of mental health treatment for depression
To start off here, we need to understand what clinical depression truly is. Depression is not a bad day or even a few bad days of tiredness, lethargy, lack of motivation. To meet clinical criteria FOR depression, an individual must have 14 or more days of 5 or more of the following: depressed mood, anhedonia, loss of interest, diminished ability to concentrate, suicidal ideations, changes in weight, psychomotor agitation, feelings of worthlessness, AND additionally, have significant impairment in occupational and social obligations. These must be pervasive and last for at LEAST 14 days. These are not triggered by psychosocial stressors, these are symptoms that hit regardless of what life is currently trying to throw your way. This is what is (supposed) to differentiate between “adjustment disorder depression/situational type” and “chemical imbalance type of depression”. This is what the DSM has taught us mental health providers to look for in screening for major depressive disorder.
Treating depression has been big business for over 70 years. Prior to the deinstitutionalization of mental health treatment, medicine had us believing that depression was caused by the monoamine hypothesis of depression; monoamine oxidase inhibitors (MAOI’s) were the drug of choice. This hypothesis believed the brain was depleted of serotonin, norepinephrine, and dopamine that medications could “replace”. There was one small problem with MAOI’s: they were horrible for people who ate foods high in tyramine. If you took a MAOI, you had to avoid things like bacon, cheeses, smoked foods like ham, sausage, the list is quite extensive of foods with tyramine in them. If you consume those foods while taking a MAOI, you could experience hypertensive crisis and a possible stroke. This led to the MAOI class of medications being discontinued fairly quickly, as the risks were outweighing the benefits. But the medical/psychiatric world still latched onto the monoamine hypothesis of depression, and they created a NEW line of meds.
And that was the birth of Tri-Cyclic antidepressants, or TCA’s. Things like Amitriptyline, Nortriptyline, and Imipramine. Interestingly enough, these medications were geared towards all 3 neurotransmitters, but they had a much stronger affinity for the Norepinephrine reuptake site than it did for the Serotonin reuptake. Patients reported their depression felt much better, but they led to memory impairment, dizziness, drowsiness, and weight gain.
So back to the drawing board we went. Studies done on post suicide brain autopsy showed a decrease in serotonin levels. This is what led to the birth of the SSRI. Prozac specifically. They created a drug that focused on the stronger affinity for the Serotonin reuptake rather than the norepinephrine reuptake found in TCA’s.
In 1988, a new revolution began. The Prozac revolution. The introduction of Prozac to the marketplace offered a “great and beneficial” selective serotonin reputake inhibitor” to the market. A “happy pill” if you will, focused only on the presynaptic uptake of Serotonin, without the TCA side effects. It was the first in line for this drug class, with others such as Paxil, Celexa, Lexapro, and Zoloft to follow shortly after. The SSRI was the new depression drug revolution. They took it a step further, and decided to make a “new and improved” version of the TCA that did not affect the histaminic receptor sites that caused tiredness and dizziness, so the SNRI class was created that had an affinity for both serotonin and norepinephrine. These are your Effexor and Cymbalta medications. They also came out with the unique drug Wellbutrin, which does not affect serotonin reuptake at all; rather, it focuses on norepinephrine and dopamine reuptake with ZERO effect on serotonin reuptake. And it worked really well for depression as well.
**So at this point, shouldn’t we have realized that the serotonin model of depression was really not accurate? That the use of serotonin reuptake inhibitors alone were not necessarily the magical drug they were marketed to be?*** The article linked below shows a great history of the invention of depression medications if you want to learn more about them.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428540/
Tomorrow, I am going to dig into the paper that has rocked the world of psychiatry this past week. I wanted to lay out the groundwork for how serotonin based medications came to be, before we dive into the next portion.