Amantadine's usefulness owes a great deal to serendipity. Its effect on Parkinson's disease (PD) was discovered when patients with that disorder received amantadine for influenza A prophylaxis. Observant patients reported improvement in the signs and symptoms of their PD, and thoughtful physicians who listened to them discovered that they indeed had experienced such improvements.
Another discovery is reported in this issue by Dr. Dolamore. In a case-control retrospective study, a majority of adverse events (AEs) related to amantadine therapy occurred after 7 days of prophylaxis in elderly residents of a long-term care facility. This potentially important fact was derived from a study of the effect of decreased renal function on amantadine's toxicity—which, in this case, seemed unrelated. However, Dr. Dolamore was able to differentiate the appearance of amantadine toxicity in this patient population. Patients less often developed AEs within 7 days of starting amantadine prophylaxis for influenza A. More frequently, they developed AEs in the period from 8 to 14 days (the recommended duration) of therapy.
Limiting prophylaxis to 1 week in elderly patients may increase the risk that the duration of treatment will provide insufficient drug and they will develop influenza A, a potentially devastating illness in residents of long-term care facilities. Establishing the viability of shorter courses of amantadine to prevent influenza A while avoiding AEs will require a large, multicenter study. I believe that such a trial should be a prospective, randomized test with patients receiving amantadine prophylaxis over periods of varying durations. Given that this hypothetical study would provide data on a safer (yet still effective) use of a major prophylactic agent, it appears to be worth doing.
There are many ways to obtain information about medications. Not all of them are randomized, placebo-controlled, double-blind clinical trials. Some knowledge about medications is found in the course of another study. These nontraditional sources of drug data are open to those who are innovative, creative, and observant. The contributions of chance to medical knowledge can often be an important adjunct to classic trials.