Most of the time you’re better off taking a generic drug than the latest blockbuster drug. Not only do you save money, which is always good, but there won’t be any unpleasant surprises. It’s an annoying reality that new drugs look good on paper, but until they’re widely used, they can have disadvantages that didn’t show up even in careful testing.

But sometimes people complain that the generic drug just doesn’t work as well as the brand name product, and we, physicians and pharmacists, are quick to conclude that it’s a placebo reaction, it’s all in your head. Most of the time it probably is. Years ago, I was working in a hospital where we dispensed a lot of placebo medication. Placebo, the word comes from the Latin meaning "I please", is an inert compound that has no therapeutic effect, but gives the patient the impression that something is being done. There have been some valuable studies of the placebo reaction, and it’s very real. It’s not well understood, but it works and it’s safe.

We were making the placebo capsules ourselves, filling empty capsules with something, I forget what, but it was a harmless white powder. They weren’t very impressive looking, but they did the job. At the same time, we had been doing a controlled drug study, a double blind study with a placebo control. Some patients got the active drug, and some got placebo, and neither the patients nor the physicians knew which were which. The idea of these studies is to eliminate both the placebo effect and investigator’s bias. Investigator’s bias occurs when the physician conducting the study wants the drug to work – has a personal interest in having the trial succeed – and so reports good results even when there are none. This can be a particular problem when the drug is an antidepressant or a tranquilizer, and the only measurement of effectiveness is the opinion of the physician. In a double blind, placebo controlled study, you can look at the results from the patients on the study medication, compare them with the patients in the placebo group, and decide whether the drug had any real benefit.

When the study was over, we had lots of left-over placebo tablets. They were green, film coated tablets that looked really good, and had no effect at all. By dispensing these instead of our home made placebo capsules, we could save ourselves some work, and give the patients a much more impressive looking product. It seemed like a great idea, except that about half the patients complained that the new tablets weren’t working as well as the old ones. They had the same active drug – which means no active drug at all – but lots of people got better results from the placebo capsules they were used to.

When an established drug loses patent protection and the generic versions hit the market, we always get a few complaints that the generic doesn’t work as well as the brand name product. We, in turn, explain that before a generic drug is approved, the manufacturer has to demonstrate bioequivalence – has to produce proof that the generic formulation has the same amount of active drug as the original formulation, and gets just as much into the blood stream in the same length of time. All expectations for dosage and duration of action are based on the original product. A tablet that releases more active drug than the original isn’t better – it’s potentially toxic. A tablet that releases less drug won’t work as well. The two have to be equivalent in terms of blood levels and time. The tests are reliable, and generic products are as good as the brand name product.

In spite of this, there will always be a few complaints. Then, we, patiently at first, explain how generics are formulated and tested. The patient insists that the generic doesn’t work as well, and we summarize our previous discussion my saying "it’s the same thing!" The result is that we’re convinced the patient is wrong, or at least showing a placebo response, and the patient concludes that we’re idiots. Most of the time we’re both right.

In the overwhelming majority of cases, there is no difference between the brand and the generic, and the best explanation is placebo response – and that’s perfectly okay. But it’s wrong when the pharmacist (and it usually tends to be the pharmacist more than the physician) starts saying "they’re the same thing" in ever louder tones of voice. There can be minor differences in the inactive ingredients that have an effect on a small percentage of people. Generics may have different preservatives, different dyes, or different fillers from the original – as long as they provide the same level of active drug they don’t have to be completely identical in other respects. While the likelihood is remote, some people may be affected by these differences. It may help to ask you pharmacist if a generic is available from a different manufacturer. If there is, you might have a better response to one product than the other.

If you try two generics and neither work, there’s a good chance that your reaction really is a placebo response. That’s nothing to be ashamed of or embarrassed about, but you may want to discuss that with your physician, and try another drug. The placebo response is common, and in many respects valuable in some types of therapy, but it works best when you don’t know about it. That’s a good reason to try something else.