For decades, in trying to persuade patients to take drugs for depression, psychiatrists have given them the rationale that the medication was to “correct a chemical imbalance in the brain.”
What is the evidence supporting that rationale? It started many years ago, when Pfizer, manufacturer of the antidepressant Sertraline (Zoloft), wrote that “while the cause [of depression] is unknown, depression may be related to an imbalance of natural chemicals between nerve cells in the brain. Prescription Zoloft works to correct this imbalance”
Because Sertraline (Zoloft) was known to be a serotonin re-uptake inhibitor, it was widely assumed that it by increasing the serotonin level in the synapses, or gaps, between neurons. This was predicated on the further assumption that depression was related to a low level of serotonin in this synaptic space. The term chemical imbalance then became a “go to” cliché in the psycho-pharmaceutical view of psychiatry. While this is presented as an assumption, in fact some patients genuinely responded in a positive way. But, not all do.
However, in the subsequent frantic race to produce other kinds of antidepressant, it was found that Bupropion (Wellbutrin) also works in the treatment of depression. This medication works by inhibiting nor-epinephrine and dopamine re-uptake. This antidepressant is devoid of clinically significant serotonergic effects. It has no direct effect on postsynaptic receptors as does sertaline. Again, some patients genuinely responded in a positive way. But, not all do.
The general idea is that a deficiency of certain neurotransmitters (chemical messengers) at synapses between neurons interferes with the transmission of nerve impulses, causing or contributing to depression. According to this view, it remains unclear whether either one or more of the monoamine neurotransmitters are responsible for depression.
The problem with this view is the failure to acknowledge the fact that while a drug reduces particular symptoms, that does not mean the symptom is caused by a chemical problem the drug corrects. Aspirin will bring down a fever, but it is too much a jump in logic to conclude that Aspirin is correcting a chemical imbalance in the body.
Similarly, one cannot loosely use the term chemical imbalance to explain a gonorrhea infection when the infection responds to a dose of penicillin. In fact, bacterial diseases such as gonorrhea develop resistance to medications. I point out the example of gonorrhea because some strains of that STD are known to be drug resistant. It is instructive to know that such drug resistance is not labelled “treatment resistant.” When anti-depressants fail to work, the depression is deemed treatment resistant. More helpful and more accurate would be to use that same label of the depression being “drug resistant.” Just as a drug resistant STD would send the physician looking for a different treatment, when a myriad of anti-depressants fail to alleviate depression the psychiatrist needs to see that their patient is not simply a chemical soup to experiment with. There are most likely other causes of depression for that patient that playing with chemistry will not overcome.
Further evidence throwing doubt to the hypothesis of depression as simply a chemical imbalance comes from the efficacy of a newly developed antidepressant, Stablon (Tianeptine), which decreases levels of serotonin at synapses. The fact is that many depressed people simply are not helped by these serotonin re-uptake inhibitors. In a 2009 study, Michael Gitlin of the University of California, reported that one third of those treated with antidepressants do not improve. Further, he reported that a significant percentage of the balance get somewhat better but remain depressed. If a chemical imbalance is the underlying cause of depression, and antidepressants correct that chemical imbalance, all or most depressed people should get better after taking them.
Neuro-imaging studies have revealed that the amygdala, hypothalamus and anterior cingulate cortex (specific parts of the brain) are often less active in depressed people. Some areas of the prefrontal cortex also show diminished activity, whereas other regions display the opposite pattern. When someone is under recurrent stress, a hormone called cortisol is released into the bloodstream by the adrenal glands. Long-term elevated cortisol levels can harm some bodily systems. It is well known that in animals, excess cortisol reduces the volume of the hippocampus.
Smaller hippocampus volume is also associated with people with severe childhood trauma. In PTSD studies of pairs of twins (not focused on early childhood trauma), where one had been exposed to trauma and the other has not, there is a significantly smaller hippocampi in the twins with trauma exposure when compared to their twins without trauma exposure. It is noteworthy that depression is almost always present in those with severe childhood trauma and it is almost always a part of the Chronic PTSD picture.
Thus far, there has not been established a clear or direct cause-and-effect relation between brain chemistry and depression. Chemical Imbalance is just a vague term to suggest that there seems to be some chemical disturbance associated with depression, and that certain drugs are known to alleviate depression in some of these depressed patients. The explanation is speculative and the proof is far from conclusive. It is not known if the depression generated the chemistry or if the chemistry generated the depression. Depression almost certainly does not result from just one change in the brain chemistry. A focus on any one single piece of the depression puzzle—be it brain chemistry, neural networks or socio-psychological stress (for example a recent or remote past stressor) is gross simplification.
From a clinical point of view, depression as a symptom began to assume the status of a disease. It is akin to classifying a fever as a disease, rather than as a body reaction to a stressor. Internal medicine has not gone taken that step: We still limit ourselves to documenting fever for investigation to look for its root cause. In psychiatry, that limitation of distinguishing symptoms from disease has gradually eroded to the point where we are bending the diagnostic criteria for making diagnoses. We can now “diagnose” the illness as “Major depression” or “Bipolar affective depression.” In short, we have selected a bunch of symptoms, put them together and call it a syndrome, a disease.
The psychiatrist may be eager to find a disorder that comes with a textbook protocol of pharmaceutical remedies. In fact, to make a diagnosis of either major depression or bipolar, the symptoms have to satisfy a stringent list as laid down in DSM 5. Often anxiety and agitation may be interpreted as hyperactivity mimicking hypomania. Bipolar is easier to “treat”, as there is a standardized algorithm to follow. Once diagnosed as bipolar, the main treatment approach is pharmaceutical.
Arriving at a DSM 5 psychiatric diagnosis does not and should not make therapists feel satisfied and over-confident to the point of ignoring other complicating and contributing factors influencing the clinical features. The danger today is the false confidence a therapist has once a bipolar label is established, the entire attention is focused on an exclusively pharmaceutical approach. One then has the protocol of waiting for the medication to work, which usually takes weeks. If the medication in adequate dosages fails to work after a few weeks, should one double the dose and wait again? That is certainly one part of the protocol promoted by the pharmaceutical companies’ guidance.
If the patient starts self-destructive behavior, does it mean her depression is worse, or she is feeling hopeless. Perhaps her children are being taken away for adoption because she is considered to be an unfit mother. Would that not be a reasonable, non-chemical imbalance based cause to be depressed? I have seen numerous examples of cases where once the focus is placed on pharmaceutical treatment, it is as if all socio-psychological factors impinging on the life of the patient can be and are ignored.
We know quite little about depression on a molecular level. Given the multiple reasons for the etiology of depression, to call depression a chemical imbalance in the brain is reminiscent of the classic story in which a group of blind men each touch just one part of an elephant to learn what the animal looks like. If one man happens to have touched the tusk of an elephant, he would swear that the elephant is like a cylinder of polished hard wood while another touching the elephant’s stomach would swear it was like a wall. The catchphrase “chemical imbalance” suggests a phenomenon associated with depression. But, association does not necessarily mean causation.
We really know very little about depression as a disorder. What we do know is that in patients with depression, less than half (roughly speaking) may have their symptoms alleviated by taking an antidepressant.
I am not against the use of antidepressants in treatment. I have witnessed effective and even dramatic responses to antidepressants in some patients. However, I am totally against mechanistically calling a symptom a disease and blindly prescribing a pill for that symptom – especially when the symptom is often a normal emotional response to real life circumstances. Such a course of action can keep a person dysfunctional for years. With that mechanistic view, treatment will be fundamentally limited to finding the magical antidepressant that works, or, at best, one that produces the least harmful side-effects.
While common sense and the history of psychiatry dictates that psychotherapy should be the first line of treatment when someone displays mental health issues, in their eagerness to expedite recovery, psychiatrists starting treatment with pscho-active drugs may lead them to ignore psychological factors for depression, such as severe childhood or other trauma.
Ultimately, which patient should be prescribed drugs as a priority is a matter that should be determined by an experienced and compassionate psychiatrist. To understand the causes of depression, we have to see the entire person, rather than just looking for a chemical disorder called depression. We have to maintain a strong index of suspicion for hidden or affirmatively ignored childhood trauma. It is imperative that we therapists always look at the patient as a person, with mind, body and spirit. Only deep listening and empathy can help to bring to awareness, in both therapist and patient, those significant factors that can manifest as depression. We should not attend to just the brain chemistry in a patient with depression. Just as when a car is by the side of the road, we do not just assume that the battery has died. It may be that the driver has run out of gas or is taking a nap!
Anyone can practice medicine if all he does is to prescribe aspirin for fever, a broad spectrum antibiotic for infection, a pain-killer for pain and a steroid as an anti-inflammatory. These are standard non-specific medications for common symptoms in general practice. Such a practitioner will help some people with some illnesses that those non-specific medications can benefit. He will cause harm to virtually all others due to this lack of insight and lack of a proper index of suspicion for the many diseases that actually affect people.
Depression is a common symptom for almost all patients coming for the first time to see a psychiatrist. Prescribing an antidepressant as soon as one sees depression in a patients is a cop-out that can have enormously bad consequences. Psychiatry must be on guard against the brain-washing influence of both the pharmaceutical industry and the insurance companies as the payees of the health care providers. We must not embrace “chemical imbalance in the brain” as the answer to the question of depression. Far too many working in the Mental Health field have fallen into that way of thinking. We need to wake up and re-examine our basic understanding of human beings again. The obligation to our patients is their well being. Our depressed patients are not just simply pools of chemicals that are not in balance!
