Older adults are often prescribed many medications. If a patients takes five or more medications, it's called polypharmacy. Polypharmacy leads to increased risks of drug-drug interactions, adverse effects, of poor compliance by patients. Polypharmacy leads to increase in hospitalization rates and also increased overall death rate. There is an Israeli study that looked at patients who were 82 years of age on average. They used eight medications on average. And then they stopped about four or five medications. And they found out that only 2% of elderly patients actually required the restart of those medications that were discontinued. Almost 90% of patients reported global improvement in their health and well-being. You led a major Italian study for over the 10 years of polypharmacy in elderly patients. What lessons have you learned from studying polypharmacy in elderly patients? What are the lessons that people around the world can take, especially when it concerns the elderly patients and polypharmacy?

You explained in an impeccable way everything. So there is very little I can add. I can perhaps add this. Why is polypharmacy so frequent? Why do my colleagues prescribe so many drugs? What can be done to improve the system? Even though you have tackled already the problem of polypharmacy, the prescribing and its efficacy. Stopping polypharmacy has a positive effect on the survival of all people.

Why do physicians prescribe so many drugs to older adults? This is very simple. Polypharmacy happens because older people have almost inevitably multiple diseases. As a consequence of multiple diseases, older patients very often see many different physicians. Each one is an expert on different organs that are affected. So elderly patients see a cardiologist, this is one of the most frequent problems. They see a pulmonologist for the lungs. They may have digestive problems, so they see a gastroenterologist. And these doctors tend to prescribe independently the drug recommended according to their guidelines for a given disease. For example, a cardiologist sees a patient with heart failure or hypertension, two of more frequent problems, or a patient with coronary disease. A pulmonologist sees a patient for COPD or asthma. A gastroenterologist sees a patient because he may have some problems of gastritis, perhaps due to the fact that they take every drug. But anyway, gastritis can also occur in elderly patients. And so on. I could mention nephrologists, rheumatologists, drugs for the treatment of arthritis. That is very frequent.

The problem is that doctors follow their guidelines without integration. And nobody is doing the integration. In other words, okay, putting together the therapeutic indications of the cardiology with other areas. Unfortunately, this is, of course, one of the problems. It is only in organ. Noone sees the person as a whole. That's a problem now. That's where the global doctor comes about. Who are the global doctors? They are the general practitioners, the internists (I am), and the geriatricians. Unfortunately, it happens very often that people go to somebody with a purpose of integrating their multiple drugs and to see what is really necessary and what is not dangerous. As you mentioned, the problem you explained very well is that the drugs interact between them. As I said before, a 'pharmakon' in Greek means 'poison.' It means also something beneficial, it means a 'drug'. So that's a problem - the lack of integration, the prescription of the basis of the guidelines for each single disease, not taking into consideration the problem as a whole.

The doctors who should do this integration are those that I mentioned, the general practitioner, the internist, and the geriatrician. Even though it is possible that every organ specialist should be especially cognizant of what problems they may create by giving drugs that sometimes interact. The answer is the overprescribing medications that you mentioned already. Judicial prescribing means reviewing all different drugs that patients are taking. It means finding out who prescribed medications. It means evaluating prescribed drugs on the basis of knowledge maybe not as deep for a specific organ, but on the basis of general broad knowledge of this generalist physician. By the term 'general physician,' I don't mean something derogatory, but I mean something positive that they have and the organ specialist has not. It is inevitable that you tend to be in that very moment, when your main problem may be the heart or the lungs or the gastrointestinal tract. But the problems should be seen as a whole.

Deprescribing, as you mentioned before, is very important. It was demonstratable, what you mentioned before, the effect of this clinical study. That remains very accurate, and there is no need to reiterate its results. You must do a good deprescribing or at least review of the drugs and the evaluation of the pros and cons of medications used. You must consider the risks of drug-drug interaction and the costs of many drugs and the risks of noncompliance. There may be a situation when you are not taking the essential drugs. Or you may take those drugs that are essential, but you also take drugs, like a proton pump inhibitor, just because you take maybe so many drugs that you have gastritis. So, there is a prescription cascade, whereby the multiple prescriptions cause other diseases. And you don't understand that these diseases are just caused by the drugs that you take. They are not due to something that hits particularly old patients.

I can give you an example of the action we undertook on our initiative in 2008. So, now it was more than ten years ago. We did showed that the division of internal medicine that used our information registry of drug-drug interactions, and we also directly supplied this system free of charge to other doctors. Doctors can see the drug-drug interaction and also the degree of interaction between medications. We have shown the results of those doctors who followed the registry and participated in this study called REPOSI (Registro POliterapie SIMI Società Italiana di Medicina Interna). They improved (reduced) the number of drugs that they prescribed. Those doctors who prescribed regularly, they continued to prescribe at an average rate in the whole of Italy. So, we went from six drugs prescribed on average to four drugs. It is good but could be even fewer drugs. But anyway, this shows that this registry is helpful. The supply of this so-called INTERCheck software, you can find it in the the web, it is supplied free of charge by the Mario Negri Institute together with this research hospital and the Italian Society of Internal Medicine, it is the sponsor of this registry. This is done on a voluntary basis, we have no funds for that. It is done voluntarily. So we also, besides publishing a lot of papers as evidence of deprescribing, the most obvious result was alerting doctors to the drug-drug interactions that matters. We looked at the reduction of an average number of drugs used by doctors in this registry. Okay, on average it was reduced from six to four drugs. We hope that at least we avoided the more than 10 drug prescriptions, that is very frequent. And also we saw that the polypharmacy, which is more than 10 drugs prescribed, has become less frequent.

So this is what we have achieved. Fortunately, the Italian drug agency became cognizant of our efforts. Next week we are going to Rome to a meeting in which we will discuss this issue of polypharmacy. And it's important that the Ministry of Health and the IFA, the drug agency, is aware of this work. This also has implication on drug costs. Because many of these drugs are wasted, they aren't useful, they represent a cost for our National Health Service. Plus, there is the risk for the individual citizens. So that's what I can tell you. The deprescription is the answer. There are some indications of how it should be done. You mentioned already, you mentioned already the result. As I told you this is just an exercise that hopefully is going to be reproduced in other countries. For instance, in Spain, they are considering it. Deprescribing study has shown some efficacy, which was already shown in the study that you mentioned in Israel. And in New Zealand, where deprescribing also happens. There is more doctors who are are more cognizant of this problem.

And the problem is, unfortunately, that there should be more knowledge of polypharmacy among organ specialists. They tend to go ahead, looking only at the organ they are in charge of. And again, this is something I may be biased against, being a generalist doctor who believes to know everything. But this is a problem. You see, a specialist, specialization became very important in the 80s, or the 70s, of the last century. There was so much progress in medical technology. And of course, it was very difficult to keep pace with the progress of technology, particularly for the internists, or the general practitioners, and the geriatricians. But very often the specialists tend to forget, particularly the youngest people who were not trained adequately in general medicine. They tend to focus too much on technology, and not to look at the patient as a whole. And this is probably the problem. We are not, of course, the best example because I told you, that even the Italian Society of Internal Medicine, when we started our registry, there were a lot of problems. But at least we have shown that there is some degree of improvement. If you tackle the issue of polypharmacy, you don't devote yourself only to it. I do it myself. I am an expert of relatively single disease, like bleeding disorder or thrombosis. That's why in the last part of my career, I thought that due to the aging of the population, perhaps my age, one should become interested in this problem of polypharmacy.

Thank you. No, that's very important because clearly, as the population ages, as more and more specialists are focusing on a particular organ, then polypharmacy continues to be a very big issue. It has to be tackled from the point of view of primary care physicians, from geriatricians and internal medicine physicians, because they are the ones that can really pull those levers.