We Have Happy Pills, Anxiety Drugs, and Therapists Galore: So Why Are We More Stressed and Depressed Than Ever?
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The first antidepressant drug was discovered serendipitously in 1952. Iproniazid, an antimicrobial agent being studied as a possible treatment for tuberculosis, was found to affect mood, making even terminally ill patients cheerful and optimistic. Investigation of a possible mechanism for this unexpected psychoactivity revealed that the drug blocked enzymatic breakdown of all three major neurotransmitters: norepinephrine, dopamine, and serotonin. Pharmaceutical chemists then looked for other drugs with this action and soon after produced a different class of antidepressant drugs by modifying the phenothiazine tranquilizers. These became known as tricyclic antidepressants, of which amitriptyline was the prototype; Merck pharmaceutical company gave it the brand name Elavil. In 1961, the FDA approved Elavil for the treatment of major depression, and it quickly became a bestselling drug. The tricyclics appeared to work by blocking presynaptic reuptake of norepinephrine and serotonin without affecting dopamine.
Because all of the early antidepressants had unpleasant side effects and serious potential interactions with other drugs and medications, pharmaceutical chemists continued their search for better ones with more specific action. But what specific action should it be? Some thought deficiency of norepinephrine was the biochemical cause of depression. Others argued for a serotonin hypothesis of depression and looked for compounds to prevent its breakdown or reuptake. The proponents of the serotonin hypothesis would win the day; their big discovery came in the 1970s, again, interestingly enough, as a result of work with an antihistamine.
Very likely you have taken Benadryl (diphenhydramine) at some point in your life. It is one of the oldest and most widely used antihistamines, the first such drug to be approved by the FDA for prescription use, in 1946. Benadryl is so sedating that it is now sold over the counter as a sleep aid. In the 1960s, this tried-and-true drug was found to have an action independent of its effect on histamine: it selectively inhibited the reuptake of serotonin. By modifying this molecule, scientists at Eli Lilly and Company in the 1970s came up with the first safe and effective selective serotonin reuptake inhibitor, fluoxetine, much better known by its brand name Prozac. The rest is history. Today the accepted biomedical explanation of depression is that it results from a deficiency of serotonin at synapses in key areas of the brain; therefore, boosting the activity of this neurotransmitter with drugs that block its reuptake will treat or cure the problem.
It’s a good bet that thirty years ago, not one American in a thousand had heard of this neurotransmitter—or any neurotransmitters, for that matter. Today, when you Google serotonin, about 11 million results appear, and Amazon sells nearly three thousand books with the word in the title (including The Serotonin Solution: The Potent Brain Chemical That Can Help You Stop Bingeing, Lose Weight, and Feel Great). “Serotonin” is the name of a professional wrestling team and an album by the British rockers The Mystery Jets. You can even proclaim your autumn blues to friends by way of a greeting card that reads, “The leaves and my serotonin levels are falling.” A once-obscure neurochemical has become pop-culture currency, and increasing levels of this feel-good compound has turned into a public obsession.
None of this just happened on its own. In order to sell antidepressant medications, drug manufacturers launched a relentless worldwide marketing and public-relations campaign promoting serotonin as the distilled biochemical essence of happiness. The message was that selective serotonin reuptake inhibitors—SSRIs—increase synaptic levels of serotonin in the brain by slowing its rate of reabsorption by presynaptic neurons, ending depression. Psychiatrists and other physicians got the technical version of this message, while consumers got a simplified one, often reduced to the rallying cry “Boost serotonin!”