Dangers of Long Term Medications
Americans, with 5% of the world’s population, take 38% of the world’s prescription medicines.
So here’s the concern, touched on in the preceding chapter but unfolded in detail here: the long-term use of almost any medication is problematic, according to almost anyone except the manufacturer. In some cases, it is even likely to shorten your life—especially if the medication is only controlling the symptoms of a condition, not addressing its cause, as most are. Many people are vaguely uneasy about the drugs they take but are not sure what to do about it. I encounter this repeatedly.
The setting was beautiful, a garden-like backyard lunch on an early fall afternoon for my wife and me. The other couple learned I was writing a guide for personal protection against medical errors. They were both on Lipitor (atorvastatin), the second most prescribed drug in the US, with 105 million prescriptions written in 2019. It was clear that they were uneasy about its long-term use but had no source for estimating their risk of long-term health-damaging effects. Nor did I at that time. How could this be? There were no clinical studies of the long-term effects of the number two drug in the world, taken by tens of millions of Americans?
It turns out there are some medium-term studies on Lipitor, but they are only discoverable by digging through peer-reviewed journals. They get a mention on WebMD but only with a phrase. I did some digging. To their credit, independent researchers are looking at the association between the long-term use of Lipitor (atorvastatin) and its rival cousins, pravastatin and rosuvastatin, with respect to the onset of type 2 diabetes. And here’s what a recent journal report said. “More recent metaanalysis of observational trials confirms and reinforces the increased risk of diabetes mellitus with statin use. Although it has been suggested that treatment of 10,000 patients for 5 years with an effective regime (40 mg atorvastatin daily) would yield between 50 and 100 new cases of new-onset type 2 diabetes mellitus, this is far outweighed by the beneficial effects of statins on coronary vessel disease.” By the way, that last comment is not only unproven but gratuitous—editorial comments like that have no place in a research article without citations.
In other words, to get all these alleged, unproven cardiovascular benefits, small numbers of patients have to “take one for the team” in terms of acquiring type 2 diabetes. This approach to the long-term effects of popular drugs is not an issue if patients get to understand the risks themselves and then choose the drugs anyway. It is a big problem if they know nothing about the risks. That’s a problem this chapter is designed to help you with.
How did this situation develop in US medicine?
The Drug Approval Process
In the US, the Food and Drug Administration (FDA) is the agency in the executive branch that reports to the president through the US Department of Health and Human Services (HHS) and is responsible for regulating pharmaceuticals and medical devices.
The FDA has a “sophisticated and complex system” for ensuring that drugs are “safe and effective,” a phrase that has been in use for decades. The review process is based on ensuring those two qualities. The public’s level of knowledge about the FDA’s process took a large jump forward during the development of COVID-19 vaccines when Operation Warp Speed achieved the approval of a vaccine in under a year, a tribute to the FDA’s flexibility under duress. Many people came away very impressed.
But let’s take a look at the process of approving a drug in the context of understanding why long-term dangers remain for many drugs. The process begins in the laboratories of drug manufacturers and startups. The pharmaceutical companies have hundreds of investigations going at any one time, focusing on lab work and animal testing. But when they find something of great interest, they submit a formal investigational new drug application to the FDA. That submission, if approved, allows clinical trials to begin on humans in three phases.
Phase I studies on humans are typically done with about twenty to eighty healthy paid volunteers. The focus in Phase I is on toxicity and safety. If Phase I studies show acceptable levels of side effects and no immediate toxicity, then Phase II begins. This time, the focus is on effectiveness, and the volunteers, from a few dozen to 300 or so, usually have a condition the drug is aimed at affecting positively.
At the end of Phase II, a plan is developed for a major clinical trial, usually up to about 3,000 people (but 20,000 to 40,000 with the COVID vac- cines). About that time a formal new drug application (NDA) is submitted.
For standard drugs, the FDA is required by law to agree to review it or reject it within sixty days. Then it is required to complete the review process (for 90% of drugs) within ten months. The Phase III data are also reviewed by an independent review board, which became even more important in Operation Warp Speed for the COVID vaccine. For instance, the emergency use authorization (EUA) for the Pfizer COVID-19 vaccine was approved by the review board by a vote of 17 to 4 with one abstention.
There are criticisms of the process to be sure, mostly focusing on the economic incentives which lead big companies to “reshape” data at times and to write off major fines for doing so as the cost of doing business. And some of the critics who have worked in the industry are outraged. In 2013, Peter Gotzsche wrote a book, Deadly Medicine and Organized Crime: How Big Pharma has Corrupted Healthcare, penning over 300 meticulously documented pages.
Some now question the whole process of clinical trials undertaken by the FDA and pharmaceutical companies where the two entities get too cozy. For instance, Marcia Angell, former editor of the prestigious New England Journal of Medicine, said in 2010 that “it is simply no longer possible to believe much of the clinical research that is published. … I take no pleasure in this conclusion, which I reached slowly and reluctantly over my two decades as an editor.”
But our purpose here is not to reform the FDA or tilt against Big Pharma. Our purpose in this guide is to keep you safe from long-term drug damage. We have two points to make. One is that many highly damaging effects of drugs don’t come to light in the relatively short-term time frames of drug approvals, however thorough they may be.
And the second point is that when taken long enough, any drug, that interferes with the natural processes of the body (let’s say its natural production of cholesterol, for instance, as statins do) may eventually affect your lifespan in some way. Let’s underline that last point because this is a major principle in acquiring medical wisdom. Most people do not think that way about drugs, just as most people think, unwisely, about cancer in a binary way—e.g., if there are abnormal cells anywhere in your body, they are going to kill you—and then they act accordingly.
Here are just three examples of our first point—some drugs don’t give up their secrets until they’ve been out there a few years. Such is the family of antibiotics called fluoroquinolones, in wide use the most recognizable brand name of which is Cipro (ciprofloxacin). Reports of serious adverse events began emerging. In 2008, the FDA put a “black box warning” on the labels of all quinolones, warning of tendinitis and tendon rupture, especially in older adults, perhaps hoping that would take care of these newly discovered dangers.
But it was not to be. In 2011, the FDA was forced to add a warning for all myasthenia gravis patients of possible worsening of their symp- toms. In 2013, it added a warning about irreversible peripheral nerve damage. In August of 2015, it convened an advisory committee, which decided that fluoroquinolones should no longer be first-line antibiotics for common infections. But heavy usage went on. The FDA has now received more than 60,000 complaints about irreparable harm, and tens of thousands belong to an online support group describing themselves as “floxed.” In 2018, mental health problems were added to the list for fluoroquinolones. All this emerged more than a decade after initial FDA and independent panel approval. Although the FDA requires manufacturers to keep a log of long-term side effects as a condition of the approval process, the situation has to get pretty bad for the FDA to order a product off the market. Subtle long-term effects don’t make the news. There are many more examples of longer-term adverse effects that do not show up in the approval process. Elmiron (pentosan polysulfate sodium) is a drug for a painful bladder condition called interstitial cystitis—a condition that affects several million Americans each year, many of them women. Elmiron has been on the market since the late 1990s and has provided relief for many, helping with the pain from this incurable condition. Before June of 2020, the labels on Elmiron said nothing about a big problem that was brewing in the background and has now triggered multiple lawsuits. The problem is maculopathy, a condition that can lead to blindness and that many doctors may mis-diagnose as age-related macular degeneration.
Probably the most recent and best-known example of a drug with a known long-term side effect is Zantac (ranitidine), approved by the FDA in 1986 and thought to be so benign that it was available in both prescription and over-the-counter strengths to treat heartburn. It turns out Zantac has had a cancer-causing contaminant in it for years called nitrosodimethylamine. The drug has been taken off the market, and lawsuits are piling up.
And now the broader class of drugs to which Zantac belongs, called proton pump inhibitors (PPIs), used to treat heartburn and the more serious esophageal reflux syndrome called GERD, is also in trouble. PPIs are a $10 billion drug class in the US that remain very effective for short- term use. Long-term use is another topic, however, because PPIs inhibit the body’s ability to make gastric acid, which protects us in multiple ways. So even the over-the-counter versions of PPIs like Prevacid, Nexium, and Prilosec, if taken long-term, are now associated with increased risk of pneumonia, bone fractures from loss of calcium, acceleration of dementia, and C. difficile colitis. All of this suffering incurred trying to alleviate a condition that is strongly influenced by dietary choices and weight, and that some believe has a strong mind-body connection.
Let us return to our prior topic—patients who are unfortunate enough to be part of the very small percentage who acquire type 2 diabetes from statins. Diabetes is a life-shortening condition, but at least it’s manageable. This is not so with the complications that arise from newer, more complex drugs today; many of those complications are very difficult to treat.
For that discussion, let’s look at one of the highest revenue drugs in the US today, and one of the most heavily promoted. It’s called Humira (adali- mumab). US sales were $13.7 billion in 2019. Drug maker AbbVie averages an astounding $5,243 in revenue for every prescription sold. At that price, it certainly might be fair to ask about long-term effects of Humira? And at that price you might guess Humira is prescribed for a rare stage IV cancer. Nope. It is prescribed for moderate to severe rheumatoid arthritis, psoriasis, Crohn’s disease, and a few other conditions, all of them increasing in the US population—a hugely successful drug.
How could it be useful for all these conditions? Because it is an immunosuppressant, and those diseases are all autoimmune conditions. Humira is what’s called a tumor necrosis fastor (TNF) blocker, which blocks the activity of TNF, a protein involved in inflammation.
As stated daily on television, side effects of Humira may include tuberculosis; serious viral, bacterial, or fungal infections; and T-cell lymphoma. Doctors generally inform patients of these risks, which increase with long-term use. Fair enough. But what are the actual plain language risk numbers so that patients can make their own informed decisions? They are researchable, and they are generally available to physicians if they study the prescriptive literature with calculator in hand. But they are not available for consumers in understandable terms. It turns out, for instance, in the clinical trials, that “T-cell lymphoma of a particularly virulent kind has occurred in 3.19 people per 100 patient-years with Humira.”
The sample size was 7,800 people. Solving for that, which few physicians would do, means that just .03 patients would get lymphoma per patient year. But multiplying that by a million Humira patients in the last ten years means over 300 unfortunate souls have gotten lymphoma from taking Humira. Again, this poses no problem in the case of truly informed consent for short-term use, but a big problem for long-term use without specific risk numbers.
Humira provides blessed, if sometimes temporary, relief for many sufferers whose lives are miserable. So, many would have elected to try Humira anyway. But the lack of decipherable consumer information for medium-range side effects with Humira, a drug that is doing about $20 billion in world-wide sales per year, needs addressing. If you are taking a long-term drug, you owe it to yourself to know whether it addresses the cause of your condition instead of the symptoms only and know what the long-term risks are. This chapter is hopefully helping with that. I can tell you on the basis of extensive research that few independent resources are available that can help an ordinary intelligent citizen evaluate the risks from long-term prescription drug use.
Dr. Sidney Wolfe, founder of Public Citizen’s Health Research Group, is an exception. He has been on this issue since 1971. He is a pioneer and a hero, and his website at worstpills.org is a source of valuable information on the latest in drug interactions, FDA recalled drugs, and potential short-term risks. But even he does not focus on long-term risks of the most popular classes of drugs or their ability to shorten your lifespan.
The Facts
- Long-term risks with many common drugs like the ones above are poorly understood, and there are few incentives in our system to understand them better.
- Many of these long-term drugs control lab-measured indicators that have not been proven to have any effect on mortality.
The Path of Wisdom
- Exhaust all paths to natural solutions before you agree to go on long-term medications.
- Diligently seek to learn the long-term risks of specific medications, and then make an informed decision.
- Understand that the risks of many medications remain undocumented.