Brain chemical imbalance

Interestingly, the instability of vata energies in Ayurveda corresponds with the Western scientific notion that a serotonin deficiency is the most common problem associated with depression. Just as vata energies can become unbalanced even in pitta and kapha types, so can serotonin become deficient even in people with other types of brain chemical imbalances, such as norepinephrine/dopamine excess or deficiency. So when people have either vata imbalances or serotonin deficiencies, I usually try to treat those first, no matter what other problems they re experiencing. 

And yet I remain convinced that antidepressant drugs are not effective treatments and that the idea of depression as a chemical imbalance in the brain is a myth. When I began to write this book my claim was more modest. I believed that the clinical effectiveness of antidepressants had not been proven for most of the millions of patients to whom they are prescribed, but I also... 

The conventional view of depression is that it is caused by a chemical imbalance in the brain. The basis for this idea was the belief that antidepressant drugs were effective treatments. Our analyses showing that most - if not all - of the effects of these medications are really placebo effects challenges this widespread view of depression. In Chapter 41 examine the chemical-imbalance theory. You may be surprised to leam that it is actually a rather controversial theory and that there is not much scientific evidence to support it. While writing this chapter I came to an even stronger conclusion. It is not just that there is not much supportive evidence rather, there is a ton of data indicating that the chem-... 

In the next chapter I examine the data behind the chemical-imbalance theory. Others have argued that these data provide only weak support for this conventional view.381 go a step further. I do not think the data are weak at all. They are in fact rather strong. But rather than supporting the chemical-imbalance theory of depression, they contradict it. It now seems beyond question that the traditional account of depression as a chemical imbalance in the brain is simply wrong. 

Depression, we are told over and over again, is a brain disease, a chemical imbalance that can be adjusted by antidepressant medication. In an informational brochure issued to inform the public about depression, the US National Institute for Mental Health tells people that depressive illnesses are disorders of the brain and adds that important neurotransmitters - chemicals that brain cells use to communicate - appear to be out of balance . This view is so widespread that it was even proffered by the editors of PLoS [Public Library of Science] Medicine in their summary that accompanied our article. Depression, they wrote, is a serious medical illness caused by imbalances in the brain chemicals that regulate mood , and they went on to say that antidepressants are supposed to work by correcting these imbalances. 

To understand the chemical-imbalance theory, it will be helpful to first review some basic aspects of how the brain functions. The human brain contains about ioo billion nerve cells called neurons. Each neuron is like an electrical wire with many branches. When a neuron fires, electrical impulses travel along its length from one end to the other. When an impulse reaches the end of a branch, it may stimulate the next neuron, influencing whether or not it fires. 

After neurotransmitter molecules have influenced the firing of a receiving neuron (more technically called a postsynaptic neuron), some of them are destroyed by enzymes in the synaptic cleft (the synapse), some are reabsorbed by the sending presynaptic neuron in a process that is called reuptake , and the rest remain in the space between the two neurons. The chemical-imbalance hypothesis is that there is not enough serotonin, norepinephrine and/or dopamine in the synapses of the brain. This is more specifically termed the monoamine theory of depression, because both serotonin and norepinephrine belong to the class of neurotransmitters called monoamines. 

Iproniazid and imipramine seemed to work as antidepressants, but how did they achieve their effects It would be another decade before the chemical-imbalance theory was launched. In 1965, Joseph Schildkraut at the National Institute of Mental Health in Washington, DC, published a groundbreaking paper in which he argued that depression was caused by a deficiency of the neurotransmitter norepinephrine in the gaps between neurons in the brain.8 Two years later Alec Coppen, a physician at West Park Hospital in Surrey, published another version of the chemical-imbalance theory. His version differed from Schildkraut s in that it put most of the blame on a different neurotransmitter, emphasizing serotonin rather than norepinephrine as the neurotransmitter that was lacking.9... 

Here then is the logic behind the first version of the chemical-imbalance theory. Iproniazid is a monamine oxidase inhibitor - it inhibits the oxidation of norepinephrine and serotonin in the synapses, thereby leaving more of these neurotransmitters available in the brain. When depressed people take iproniazid, they get better. Therefore insufficient norepinephrine and/or serotonin causes depression.12... 

Axelrod s discovery provided an answer to the question of why imipramine might alleviate depression, even if it did not inhibit the destruction of neurotransmitters in the brain. With the problem of imipramine solved, the chemical-imbalance theory seemed to work. Two different types of drugs relieve depression, the theory went,... 

But that was only one half of the logic behind the chemical-imbalance theory. The other half came from studies of reserpine, a drug that was extracted from Rauvolfia serpentina or the Indian snakeroot plant, which had historically been used to treat snakebite, hypertension, insomnia and insanity. In studies of animals, reserpine was reported to induce sedation and to decrease brain levels of norepinephrine, serotonin and dopamine. Clinical reports indicated that some people became severely depressed when taking reserpine.14 Putting these two findings together, it seemed likely that reserpine made people depressed because it decreased neurotransmitter levels. 

How is it that the chemical-imbalance theory was proposed and so widely accepted, when the only controlled scientific study that had been done indicated that one could relieve depression, rather than induce it, by giving patients a drug that increases brain levels of monoamines David Healy, in his comprehensive treatise on the history of antidepressants, provides an answer to this question.19 The study was simply ignored, despite having been published in The Lancet, one of the world s most prestigious medical journals. 

When the chemical-imbalance theory was introduced more than 40 years ago, the main evidence in favour of it was the contention that antidepressants, which were thought to increase the availability of serotonin and/or other neurotransmitters in the brain, seemed to be effective in the treatment of depression. As Alec Coppen wrote in 1967, one of the most cogent reasons for believing that there is a biochemical basis for depression or mania is the astonishing success of physical methods of treatment of these conditions. 26 The situation has not changed very much since then. People still cite the supposed effectiveness of antidepressants as fundamental support for the chemical-imbalance hypothesis. This theory, they say, is supported by the indisputable therapeutic efficacy of these drugs .27... 

If the chemical-imbalance theory is wrong, and if depression is not a brain disease, how is it produced and how can it be prevented and treated One way to look for clues is to examine the process by which we were misled into the realm of chemistry. There is a culprit hiding in the history of the chemical-imbalance theory - a culprit that is guilty of leading doctors and patients astray over and over again in the history of medicine. The culprit is the placebo effect, and its darker twin, the nocebo effect. Depressed people got better when given MAO and reuptake inhibitors as antidepressants, and this led researchers to conclude that depression must be caused by a chemical deficiency. But much (if not all) of that improvement turns out to be a placebo effect. So to understand depression and how it might be treated effectively, we need to examine the placebo effect more carefully. That is the topic of the next two chapters. 

By now, I hope that I have convinced you that much of what has passed for common wisdom about depression and antidepressants is simply wrong. Depression is not caused by a chemical imbalance in the brain, and it is not cured by medication. Depression may not even be an illness at all. Often, it can be a normal reaction to abnormal situations. Poverty, unemployment, and the loss of loved ones can make people depressed, and these social and situational causes of depression cannot be changed by drugs. 

The importance of brain circuitry is that it reminds us that these chemical neurotransmitters are not released willy-nilly throughout the brain. This is why the term chemical imbalance is so unsatisfactory. The brain is not a large water bottle into which these chemicals are poured and maintained in some precise balance. For that reason, there is no simple test to check a neurotransmitter level like the dipstick on your car s oil reservoir. Instead, your brain is a delicate instrument with predefined but ever-adapting pathways of communication. 

Zoloft works by making serotonin more available where it is needed. This may help to correct the chemical imbalance that can cause depression. If your brain gets the right amount of serotonin, depression might improve (my emphasis). To stick with drug experiments virtually requires the belief that your biology is bad ... 

As these accounts show, people s self-esteem and sense of integrity are deeply connected to their ability to control their personal problems. The people I spoke with had difficulty accepting fully the idea that emotional illnesses are no different from physiological problems such as heart disease or diabetes. It may be comforting to hear that antidepressant medications correct chemical imbalances in the brain just as insulin controls diabetes. But most of those I interviewed assigned different meanings to mental and physical conditions. When asked directly, they affirmed that psychiatric drugs are far more likely than other medications to make them feel bad about themselves ... 

Some psychiatrists warn that Prozac is not the cure-all for emotional problems, which are usually brought on by crisis situations and not necessarily by chemical imbalances in the brain. Although Prozac is widely used, some warn that the long-term effects on the brain are not yet known. The drug should always be used under close medical supervision. 

The widespread use of expressions such as He has a chemical imbalance or Her brain is hard-wired this way when talking about children considered to have ADHD reinforces this belief. Although... 

Even when they acknowledge that there is no evidence for a chemical imbalance many psychiatrists believe that the term is still justified and appropriate, thereby demonstrating a deep underlying commitment to the idea. Wayne Goodman, a prominent United States psychiatrist commenting on an article highlighting the fact that there was no established link between serotonin abnormality and depression, still maintained that the term chemical imbalance was a reasonable shorthand for expressing that this is a chemically or brain based problem and that medications help to normalise function (quoted in Meek 2006). 

Along with this emphasis on particular disorders, recent pharmaceutical industry literature for conditions like depression and psychosis refers increasingly commonly to imbalances in brain chemicals, echoing the statements of official psychiatric literature described in Chapter 1. On depression, Eli Lilly s website claims that a growing amount of evidence supports the view that people with depression have an imbalance of the brain s neurotransmitters. .. many scientists believe that an imbalance in serotonin may be an important factor in the development and severity of depression (Eli Lilly 2006a, accessed 10.02.2006). Wyeth, makers of the antidepressant Venlafaxine (brand name Effexor... 

At this point Brodie formulated his unifying hypothesis that serotonin and NE were responsible for controlling brain function and that mental illness might be a consequence of a chemical imbalance in central neurotransmitter amines. The stage was thus set for the medicinal chemist to design molecules which would affect brain amine levels in such a way as to alter the emotional state. 

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