On today’s page of Talmud there is lots of advice. Lots and lots. Live in a city which has horses that neigh and dogs that bark, because they will provide security. Don’t live in a city where the mayor is a doctor, for he will be too busy with his job to govern properly. Then comes this
פסחים קיג, א
אֲמַר לֵיהּ רַב לְחִיָּיא בְּרֵיהּ: לָא תִּשְׁתֵּי סַמָּא, וְלָא תְּשַׁוַּור נִיגְרָא, וְלָא תִּעְקַר כַּכָּא, וְלָא תְּקַנֵּא בְּחִיוְיָא
Rav said to Chiyya, his son: Do not get into the habit of drinking medications, lest you develop an addiction. And do not leap over a ditch, as you might hurt yourself in the process. And do not pull out a tooth, but try to heal it if possible. And do not provoke a snake in your house to try to kill it or chase it away…
Today we will focus on the first bit of advice on this list - the problem of taking too many medications.
The problem of polypharmacy
There is a medical word that describes taking too many medications - it is called polypharmacy. And it is a real problem, especially in the elderly, who are often prescribed one drug after another as they see different specialists and sub-specialists. There is some debate about how many drugs are considered to be polypharmacy, but most physicians have a cut off at five or more in one person.
The Rashbam and the NIH on addiction
The Rashbam (1085-1158), grandson of the famous French commentator Rashi, gave this explanation on today’s passage of Talmud:
לא תשתי סמא - אל תשתה סמים מפני שנקבע להם ווסת ויהא לבך שואלך ותפסיד מעות ואפילו לרפואה לא תישתי אם אפשר לרפואה אחרת
Do not take drugs - Don’t take drugs because you will become addicted to them, and you will constantly be looking for them and spend lots of money. Even when they are needed to cure you, do not take them if there is an alternative.
The Rashbam’s words here could not be of more relevance to us moderns. The problem of drug addiction and the abuse of some prescribed medications is one of the leading health challenges facing the US and other industrialized nations. In fact, before the COVID pandemic, it occupied much of the attention of the US National Institutes of Health, which set up a multi-million dollar investment program to address the crisis called HEAL - Helping to End Addiction Long-Term. I played a small but I hope useful role in the effort, helping to establish a program to develop effective, non-addictive treatments to reduce the burden of illness due to pain and to reduce risk of addiction. Only a few drugs we use today have the potential to become addictive, and the Rashbam’s words do not feature in the current advice we give our patients. But when we do use these useful but potentially addictive and dangerous drugs, we must do so with the utmost care.
The Dangers of Polypharmacy
The Artscroll English translation of the passage above reads “do not ingest any unnecessary drugs.” Of course what makes a drug unnecessary is often a matter of legitimate medical dispute, but there is no doubt that taking a lot of medications - polypharmacy - can lead to some serious complications. In a recent expert review of the dangers of taking too many drugs researchers noted that “in general, polypharmacy has been linked to a range of negative outcomes, including falls, frailty, and mortality.” It is hard to tease out any causation (as opposed to any association) though, and the research is complicated. Is a person taking lots of drugs more likely to be weak and fall and get infections because of the several drugs she is taken, or has she been prescribed several drugs precisely because she is frail and at risk of these and other problems?
The outcomes associated with polypharmacy can be broadly put into four categories as you can see in the figure below. “In the inner circle, closest to polypharmacy, are drug-related outcomes, such as drug-drug interactions. As we move to the outer circles, the outcomes could potentially be related to the more proximal outcomes (e.g. drug-drug interactions can contribute to hospital admissions) and are also more likely to be affected by other health-related factors.” Here are some of the problems of polypharmacy.
A framework for polypharmacy and conceptual classification of outcomes. From Jonas W. Wastesson, Lucas Morina, Edwin C.K. Tan, Kristina Johnell. An update on the clinical consequences of polypharmacy in older adults: a narrative review. Expert Opinion of Drug Safety 2018: 17 (12); 1185-1196.
Adverse drug reactions. All drugs have side effects, and the more drugs you take, the more likely you are to experience some of those effects. In addition, drugs interact with each other, often in bad ways. In fact up to 10% of hospitalizations in the elderly are due to adverse drug reactions.
A Swedish study based on nationwide registers found that the risk of falls increased with the number of drugs used in a dose-response fashion, meaning the more drugs you take, the more likely you are to fall.
Physical function like getting out of a chair or gripping something is reduced in those with polypharmacy, though it is difficult to establish a causal relationship.
Polypharmacy has been shown to cause frailty and sarcopenia, which is a loss of muscle mass.
Polypharmacy has been linked to lowered cognitive functions and dementia. In a study of community-living Japanese older adults, polypharmacy was associated with lower cognitive status, and a longitudinal register-based (nested case-control) study matching incident dementia cases with dementia-free cases found that polypharmacy was associated with receiving a dementia diagnosis.
Polypharmacy has been linked with hospital admission in studies including general older adults, nursing home residents, and in people diagnosed with dementia. One researcher found that the risk of unplanned hospital admissions increased with the number of medications used, though this effect was less evident for people with a high number of chronic conditions.
Finally, polypharmacy has been linked with increased mortality. A 2017 systematic review (with meta-analysis) estimated that the risk of death goes up by around 8% for each additional drug taken. So not good.
The authors of this review leave us with these sobering conclusions:
The prevalence of polypharmacy in older adults is increasing in most countries. This is a cause for concern given the observed association between polypharmacy and a wide spectra of negative health outcomes, including drug-related problems, adverse drug events, physical and cognitive function, hospitalization, and mortality… scalable interventions to reduce polypharmacy (by deprescribing or other interventions) is needed to revert the trend of increasing levels of polypharmacy in the older population.
Prevention is better than cure
Commenting on today’s passage of Talmud, Rabbi Yosef Chaim of Baghdad, known as the Ben Ish Chai (1860-1930), gave this advice:
לָא תִּשְׁתֵּי סַמָּא. פירוש אם ראית בעצמך התחלת מיחוש באיזה חולי לא תמהר לשתות סם דהסם עושה מלחמה עם החולי וראוי תחלת הכל וְקָרָאתָ אֵלֶיהָ לְשָׁלוֹם (דברים כ, י) שתעשה הכנות טבעיות לשמירת עצמך מן החולי הן מצד האכילה שקורין בערבי פהרי"ז הן מצד הישיבה והמנוחה והמקום וכיוצא בזה ואולי יהיה לך זה עזר לרפואה טבעית ולא תצטרך לשתות סם לגמרי
If you begin to feel unwell from some disease, do not rush to make a drug, because the drug will wage war against the illness. But it is best…if you use a natural preparation to keep yourself healthy and prevent illness, with a proper diet, and also by sitting comfortably, getting enough rest, and paying attention to where you live, and so on. In doing so, perhaps this will provide natural healing and you will not need any drugs at all.
Just like the advice of the Rashbam, the Ben Ish Chai is also spot on. Preventing disease with exercise, a proper diet, getting enough rest and living in a healthy environment are far better for you than trying to treat a disease once it has begun. This does not mean that diseases that we can and should treat with medications are best tackled with “natural interventions.” Cinnamon does not help control your blood sugar if you have diabetes. But insulin does. Still, the advice of the Rashbam and Ben Ish Chai should be played on a loop in the waiting room of doctor’s offices and clinics. And we should listen.
