Brain chemical imbalance theory

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. 

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. 

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. 

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. 

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