Diseases can exist without anyone knowing why, and treatments can work without anyone knowing why. Quinine, for example, was used against malaria before the existence of the parasite was known, and only transmission via the mosquito was known.
Thus, the question of whether antidepressants work is independent of the veracity of the theory of depression underlying their prescription. The first antidepressant discovered, imipramine, began to be used to treat tuberculosis, so doctors noticed that the mood of some of their patients markedly improved. However, imipramine was not effective against tuberculosis.
The most popular theory about the cause of depression is that it results from a relatively low level of serotonin in the brain. (Let’s put aside the difficulties in the concept and diagnosis of depression itself, as well as the fact that the effectiveness of antidepressants in any controlled trial is often marginal.) The most common treatment for depression now is to prescribe selective serotonin reuptake inhibitors (SSRIs). , which supposedly increase serotonin levels in the brain. Between the theory of the cause of depression and its treatment, therefore, there seems to be some logical connection.
An article in the journal Molecular Psychiatry recently tried to examine the scientific evidence for the serotonin hypothesis from several possible angles and found out that she is very precarious. For me, it was no big surprise. It always seemed implausible to me that such a simple hypothesis would be correct and would still explain a disease so protean in its manifestations, so varied in its causes, so doubtful even in its nosological identity.
When I was a young doctor, there had long been a debate about whether depression was a single entity that varied on a single axis according to severity (ranging from trivial to life-threatening), or whether there were two types of depression, the reactive and the endogenous, the latter being much rarer, but capable of leading to severe melancholy, and it was not caused by anything in the patient’s life, nor by circumstances that could explain it. Politically—if not scientifically—the first alternative won. And now, as an eminent research psychiatrist says, “there’s only depression and more depression.”
Of course, this sounded like music to more than one kind of ear. All unhappiness turned into depression. In fact, the words “unhappy” and “unhappiness” have almost disappeared from the lexicon of Western man. Bodily normality was ecstasy and deviance was disease. The solution was to medicate.
These days, a new type of antidepressant has advanced: the SSRI, with a series of side effects that are apparently more benign than older antidepressants such as amitriptyline, whose overdoses were dangerous because the depressed (or supposedly depressed) were prone to take them. And the SSRI came up with a pleasantly simple hypothesis to explain its effectiveness (if it had any). A real gold mine! Before long, one-sixth of the adult population of several large countries was taking it. A pill for all ills has become a reality, if not strictly medical, at least social. The sum total of human unhappiness is difficult to measure, but it is not obvious that it has declined with the advent of these drugs.
The theory proved popular with the public, who could now explain their own discontent through a chemical imbalance in the brain, even though, for a very large part of that public, it is difficult to distinguish potassium permanganate from copper sulfate. It gave people the license to talk about themselves without revealing anything. I overheard many conversations on buses, trains and elsewhere about the chemical balance in the brain of one of the interlocutors. It’s not me, it’s my neurotransmitters. And insofar as the SSRI, like so many drugs, exerts a powerful placebo effect along with an eventual true effect, the theory seemed, in many cases, to have validity.
The whole question of human misery is of fearsome complexity. But what else should we expect? We have a thirst for simplification the way a desert traveler thirsts for water.