To review: You’re one of the many people who weren’t severely depressed in the first place but have learned to love your antidepressants, or at least to put up with them as a necessary evil. And you’ve discovered that the drugs, scientifically speaking, only work in the severely depressed. Which is sort of, well, depressing. So what to do?
To understand this, you have to know a little history. In the 1950s, Geigy whipped up a new drug that they thought would treat schizophrenia. Unfortunately, all imipramine did for schizophrenic patients was make them more agitated. There was an embarrassing incident at an asylum in Switzerland in which patients on one of the new drugs, imipramine, hopped on bicycles and rode, in their nightshirts, into the village and alarmed the citizens. But imipramine’s goose wasn’t cooked. The doctors figured that if it was stimulating, perhaps it could be used in people who could stand some stimulation–depressed people.
Sure enough, when imipramine was given to depressed patients, they got better. Now, this was in the days when you could get a drug approved very quickly, I mean if you were a drug company. Regulators didn’t require you to prove that the drug worked, only that it was safe, i.e., that it wouldn’t kill you. Efficacy was considered a matter of opinion, and drug companies cultivated opinion among doctors by giving them samples of new drugs, asking them to observe their effects, and then report on them to their colleagues. (And if you felt too lazy to write that report, the company would be glad to do it for you, just so long as you put your name to it.)
One of the doctors checking out imipramine was Max Hamilton, a British psychiatrist who had ended up in the backwaters of Leeds. Geigy asked Hamilton to develop a way to test the effects of the drugs, the better to fashion psychiatric testaments. Hamilton observed what happened when he gave imipramine to the people in his hospital who were suffering from depression. He distilled his observations into seventeen categories, ten of them physical–sleep, weight gain, etc.–and seven psychological–guilt, sadness, etc. Those categories became the items on his test, and the test became a reasonably accurate way to measure the effects of antidepressants on those items. The Hamilton Scale was not, its author was quick to point out, a diagnostic tool, but only an index of severity.
OK. Now jump ahead twenty-five years to the mid 1980s. Other antidepressants like imipramine–the tricyclics–had come on the market, some of them after the FDA started requiring efficacy data in the early 1960s. They had been approved on the basis of their performance on the Hamilton. And now there were new drugs–the SSRIs, led by Prozac. How to measure them? Well, why not use the tried-and-true Hamilton?
Actually, there were some good reasons not to. The Hamilton, remember, was designed to measure the effects of tricyclics on patients depressed enough to be in the hospital–the severely depressed, let’s call them. But in the meantime, clinical trials had evolved in such a way that outpatients were much better subjects. But outpatients tend to be less depressed than inpatients. So you had a different class of drugs being tested on a different pool of patients. It might have been a good idea to develop a different test.
That’s not what happened, and in the next post I’ll detail how this culminated in the recent revelations, and confusion, about placebo effects.
