Serotonin
Many antidepressant pharmaceuticals on the market today work by attempting to manipulate serotonin levels. Selective serotonin reuptake inhibitors (SSRIs) are among the most prominent and long-standing depression meds. Lexapro, Zoloft, Paxil, and Prozac (or escitalopram, sertraline, paroxetine, and fluoxetine, respectively) are all SSRI drugs.
Serotonin is an important neurotransmitter that plays a critical role in mood regulation. It also helps the brain efficiently send signals related to hunger, sleepiness, pain, sickness, and all sorts of aspects of our emotional state.
While much of our body’s serotonin is found elsewhere, such as in the digestive tract, it is often most closely associated with the brain due to the critical messaging roles it plays in your nervous system. SSRIs are long-term maintenance drugs designed to build up in your body over time, and, consequently, withdrawals can be serious.
Norepinephrine
An important hormone, norepinephrine is perhaps most closely associated with the “flight or fight” response that occurs when you’re faced with a particularly stressful situation. It is also central to the way your brain and body process the more well-known flight or fight hormone, adrenaline.
Norepinephrine is also implicated in the regulation of blood pressure and the dilation of blood vessels. Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a class of drugs similar to SSRIs, but they manipulate your body’s norepinephrine as well as its serotonin. Effexor XR (venlafaxine) is one popular example.
Dopamine
Dopamine is found in the brain’s reward center and can be explained in a fairly simple way — the more dopamine you have, the better you feel. This pleasurable sensation can help to reinforce positive behavior, build meaningful relationships, or motivate us to perform at a high level.
However, it also plays a central role in the development of addiction. The euphoric dopamine release triggered by drug use, for example, can feel addictive in and of itself. Individuals are also subject to building up a dopamine tolerance. This means it will require more and more of the drug to continue achieving those pleasurable effects over time. In extreme cases, the dopamine “high” eventually becomes completely unattainable due to the high dose of drugs that would be required to achieve it, essentially “burning out” the user’s natural dopamine response.
Glutamate
Glutamate is an amino acid involved in conjuring up those excited, pleasurable sensations that come with mastering a new skill or recalling a favorite memory. In addition to playing a role in human brain health, it is also a naturally occurring substance in many foods.
GABA
Gamma-aminobutyric acid, usually shortened to GABA, has also been the focus of much pharmaceutical antidepressant research. GABA helps you to process negative emotions like fear and anxiety by blocking or attenuating certain types of nervous system signals. Healthy GABA levels can help someone feel more at ease and maintain their cool in a stressful situation.
Neurotransmitters and Depression
The conventional wisdom among psychology and neuroscience experts has long held that low levels of neurotransmitters, like serotonin, norepinephrine, and dopamine, can be correlated to depression symptoms. While this holds true in a broad sense, it presents something of a “chicken or the egg” paradox. It’s not well understood or agreed upon whether a lack of these neurotransmitters is what causes depression, or the disease of depression is itself suppressing the production of these natural transmitters.
Many chemicals play crucial roles in sending signals throughout the central nervous system, and they are thus crucial components of overall mental health. However, environmental stimuli, learned behavior, and genetic factors are often just as important when it comes to someone’s overall mental health picture.
In any case, there is no evidence to suggest that “balancing” neurotransmitters or other chemicals represents some sort of cure for depression. Mental health is a deeply personal lifelong journey and not a chemical equation that can be neatly balanced with the right combination of ingredients.
The History of Chemical Imbalance
The history of the phrase “chemical imbalance” is really the history of the scientific community debating back and forth over the course of decades. Over this time period, researchers were attempting to work out exactly how significant a role the levels of certain chemicals play in our mental health. Disagreements between psychiatrists and drug researchers have often been at the core of this story.1
So, when were the first chemical imbalance theories of depression and schizophrenia proposed? Chemical imbalance entered the discourse of legitimate medical and scientific communities in the mid-twentieth century. The term can be traced back to research into affective disorders conducted by J.J. Schildkraut in 1965. Schildkraut’s focus was primarily the neurochemical noradrenaline. Could add that Schildkraut transitioned from keenly advocating electric shock to advocating drugs to treat mental disorders. Experimenting on the urine of rat brains, he devised ways to classify mental disorders as biological rather than psychological disorders. For all of the hundreds of millions of antidepressant prescriptions sold every year, only a sparse percentage of patients report a satisfactory result.6
Chemical imbalance became a buzzword in popular lexicon due to the “serotonin theory” that came into prominence around the 1990s and built on Schildkraut’s work. Serotonin theory can be summarized fairly succinctly: the more serotonin someone has, the less depressed they will be. The emergence of this theory led to a wave of research and prescriptions for serotonin-manipulating antidepressant drugs. The serotonin theory continued to be favorably referenced in influential science textbooks, and even new research, well into the 2010s.
It is likely that not all the public debate about serotonin and chemical imbalance was held in good faith. By the time researchers and doctors had begun a robust academic dialogue about the merits and limitations of serotonin-based depression treatment, there were also large pharmaceutical companies involved.
These companies were making massive profits off antidepressant drugs. Their well-funded marketing and public relations departments were willing to go to great lengths to ensure their “serotonin boosting” depression treatments continued their market domination. 2 They were largely successful. Today, antidepressant drugs represent a $15 billion dollar market, roughly the entire national GDPs of Iceland and Jamaica combined.
It now seems possible that the hyperbolic debunking of serotonin theory, combined with the well-funded backlash to that debunking, harmed and marginalized legitimate criticism of chemical imbalance theory. Claims that chemical imbalances were not actually central to treating depression were frequently dismissed as “anti-science” or “fringe.” However, they were correct in that there is a great deal more to psychiatry and the treatment of depression than simply “balancing” the body’s level of a certain chemical.
SSRI-induced Serotonin Deficiency
Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for depression and anxiety disorders. 7 Patients require several weeks or more of treatment before showing an improvement in mood, and many patients show only partial remission or fail to respond entirely. SSRIs treat depression by increasing levels of serotonin in the brain.
SSRIs block the reabsorption (reuptake) of serotonin into neurons. This makes more serotonin available to improve transmission of messages between neurons. SSRIs are called selective because they mainly affect serotonin (not other neurotransmitters).