Nuvigil, Placebo Effects, and Billions in Profits

Businessweek carried an article on a drug called Nuvigil which is a follow up to a drug called Provigil that is about to lose its patent protection. Critics of the drug industry point out that Nuvigil is merely a minor variation on Provigil that will allow the company, Cephalon, to continue charging high prices for essentially the same product that will become available as a generic. For some reason the FDA allows this, enhancing its reputation as a tool of the drug industry rather than a protector of consumers. Cephalon has combined this approach with another tried and true marketing tactic: every new drug should have a new disorder that it treats. Cephalon is touting the existence, and wide-spread incidence of “shift work sleep disorder.”

It would appear that everyone who works an irregular schedule and feels sleepy is now being encouraged to regularly consume psychoactive drugs. Remember these pills are not the same thing as a cup of coffee or tea, or a piece of candy to act as a stimulant. Provigil is also used to treat depression, ADHD, and schizophrenia. A drug that can be claimed to alter the brain function of the schizophrenic is not something people should be taking because they are merely sleepy.

The Businessweek article provided this information:

“Cephalon’s media campaign is its first to widely trumpet alertness pills by stressing the recognition of shift work disorder by doctors and sleep experts, who estimate the malady may affect one in four shift workers. Although Cephalon doesn’t claim Nuvigil works better than other approaches, the company says that between 2007 and 2009 it studied 359 shift workers for six weeks and found 77 percent of those who took Nuvigil said they were more alert for the last part of their shift and the drive home, compared with 57 percent given a placebo.”

First of all, any “results” provided by a drug company should be treated with skepticism. Independent testing generally provides different results. Also, there is no way of knowing how many samples of shift workers were evaluated in order to obtain the quoted results, and there is no way of knowing how the shift workers were selected. There are many ways to insert bias into medical trials.

Drug testing when mental states are involved are particularly susceptible to errors and bias. There is nothing to measure, and everything depends on the self-reporting of the subject. Most testing is involves providing some subjects with a placebo as a means of assessing drug effectiveness. Neither the patients nor the testers are supposed to know which subjects receive the placebo and which the drug. What is striking about the data provided is the size of the placebo effect in the quoted number: positive effects for the drug at 77%, positive for the placebo at 57%. In other words the placebo is 74% as effective as the brain-altering drug. The placebo works pretty darn well. Combine a sugar pill with a cup of coffee and you have a dollar's worth of alertness as opposed to the medically risky $12 Nuvigil pill.

This 74% placebo effect has been encountered before.

A medical researcher, Irving Kirsch, spent years trying to determine the effectiveness of antidepressant drugs. A description of his findings can be found here. Kirsch surveyed the data available in the medical literature and concluded that placebos were 75% as effective as the antidepressant drugs. Does that number look familiar? Kirsch then used the Freedom of Information Act to extract the more complete set of data that the drug companies provided the FDA. Using those results he determined that, for six common antidepressants, the placebo was 82% as effective as the drug. Kirsch also noted that drugs that supposedly had no connection with depression often worked as well as the antidepressant drugs. He hypothesized that this result depended upon the drug having a side effect that the subject could discern. To test this notion he performed a study in which the subjects were provided a placebo with an agent added that would cause a dry-mouth effect. These results indicated that the “active” placebo was equally effective as the drug. This was referred to as the “super placebo effect.” If a person with a mental condition is told that they are being given a pill that will make them feel better, they will tend to feel better. Clinical subjects can only feel confident they are receiving the actual drug if they experience a side effect—hence the super placebo result.

This suggests that the Nuvigil results could be entirely due to a placebo effect.

The moral of this story is that one should beware of all people who would encourage the taking of drugs. Not all dangerous drugs are obtained on the street. One must also take care in classrooms and in doctors’ offices. With drug companies providing much of the medical literature, doctors often only know what the drug companies tell them. And what drug companies tell them is not always appropriate. Cephalon, for example, pled guilty to criminal acts and paid $475 million in fines for misleading marketing activities in 2008. When in doubt, do your own research.