Physicians who prescribe medications like to believe that their choices are based on evidence. In fact, there is a mantra that most prescribers have embraced: “Evidence Based Medicine,” abbreviated: EBM. It represents scientifically proven treatments. Instead of tradition or intuition, this approach relies on randomized controlled trials. But there’s a problem with EBM. The inherent unpredictability of medications makes it almost impossible to anticipate the benefit or risk for any individual patient.
Patients Are Like Snowflakes:
You’ve probably heard that no two snowflakes are identical. Even so, you would have to look very carefully to spot the differences. People, on the other hand, usually look distinct. That’s why facial recognition programs are effective.
People differ in many more ways than their fingerprints or the shape of their eyebrows. Some people love spicy food, while others can’t stand it. Musical tastes are even more varied. Some people love bluegrass or gospel music. Others adore jazz or classical. Then there are people who prefer rap, R&B, baroque or blues.
People also differ dramatically in their response to medications. Some people are “slow metabolizers.” That means they are less able to process certain drugs. These compounds may linger and accumulate in the body. A “standard” dose may be excessive for such individuals.
On the other hand, a rapid metabolizer may eliminate medications faster than “normal.” As a result, a standard dose may not work very well for such people.
Coffee/Caffeine and Slow vs. Fast Metabolizers
People learn pretty quickly if they are fast or slow-metabolizers of caffeine. If you are super sensitive to caffeine, chances are fairly good that you are a slow metabolizer. That means you have two modified forms of the CYP1A2 gene that breaks down caffeine.
You have about one-fourth the processing power that fast metabolizers have. These are people who can drink a cup or two of coffee in morning and in the afternoon or evening and go to sleep without a care in the world. Super slow metabolizers, on the other hand, often find that just one cup of coffee after noon can keep them awake at night. Caffeine can linger in their bodies for 8-10 hours or longer.
Drug Companies Rarely Take the Unpredictability of of Medications into Account:
When it comes to medications, drug companies often behave as if most people respond the same way to the same dose. That is not always the case.
It’s not just genetic variability and metabolism, though that can be extremely important. Some people are just super sensitive to many medicines. Others react in paradoxical ways that don’t make much sense to drug company marketers.
The Unpredictability of Medications Like Benadryl:
Diphenhydramine (aka DPH and/or Benadryl)
Antihistamines are extremely popular. Take diphenhydramine (Benadryl) as an example. This was the first prescription antihistamine approved by the FDA in 1946. It became available over the counter in 1982.
Diphenhydramine usually works well against allergies. It has one common drawback–it makes most people drowsy. As a result, lots of people prefer to take it at night, when they can sleep, rather than during the day when it might interfere with their ability to concentrate, drive or operate machinery.
Several companies even take advantage of this effect, adding DPH to their nighttime pain relievers. Medicines like Advil PM, Aleve pm, Excedrin PM, Tylenol PM and ZzzQuil contain diphenhydramine to help people feel sleepy. We do worry that long-term use of anticholinergic antihistamines like diphenhydramine may affect the brain. You can read more about this concern at this link:
“Will Sleeping Pill with Diphenhydramine Lead to Memory Loss?”
A Paradoxical Stimulant Effect of Diphenhydramine:
Not everyone reacts to DPH with drowsiness, however. One reader told us:
“People use Benadryl as a non-addicting sleeping pill because it can make them drowsy. Rarely, some people develop a paradoxical reaction and become agitated. I learned this when I gave my toddler a test dose of Benadryl. He flew around the house for several hours.”
This reaction has been noted for children, but it can also affect adults.
Another person wrote:
“Unlike many people, I feel agitated, not drowsy, when I take Benadryl. It also gives me restless legs.”
The Unpredictability of Medications like Gabapentin:
In an effort to reduce opioid reliance, doctors often prescribe the epilepsy medicine gabapentin off-label for pain or mood problems. Some people find it extremely helpful.
Steve wrote:
“I have been taking gabapentin for 12 years for anxiety and can tell when I miss a dose or lower it. It has helped me greatly.”
However, other people have quite a different experience with this drug.
Here’s what another reader said:
“My dog has been prescribed gabapentin for pain after surgery. She did well on it. I took it for post-shingles pain, and it affected my ability to think. This lasted for several weeks after stopping it.”
The Unpredictability of Medications Like Ozempic and Wegovy:
The GLP-1 agonist semaglutide (Ozempic, Wegovy) has been getting a lot of attention because it helps control blood sugar. Many people taking this medicine also lose weight.
Harold is delighted:
“I have been taking Ozempic for 16 months with no serious side effects. I have type 2 diabetes. For years, my A1C was over 7 and nothing helped. On Ozempic, my A1C has been 5.6 or below. I have lost 45 pounds and I am not hungry.”
On the other hand, Agatha reported:
“I was on Ozempic for 6 weeks. I was constantly nauseated and vomiting. I lost 15 pounds but I could not tolerate the medication. After stopping it, I gained 10 pounds back in two weeks.”
The Unpredictability of Medications Like Statins:
Statins are the most prescribed drugs in America. At last count, 28 million people are taking atorvastatin. Another 10 million are on rosuvastatin. And 6 million are swallowing simvastatin. For people who have suffered a heart attack, such drugs may reduce the risk of a recurrence.
Some people tell us that statins are great. They lower LDL cholesterol with no side effects. Others, though, report some pretty devastating complications. As far as we can tell, there is not a lot of predictability when it comes to adverse statin side effects.
Paul had a number of problems on atorvastatin:
“I have been taking atorvastatin for years. I still remember that not long after beginning to take it I experienced muscle pain, especially in my legs, and memory issues. My blood sugar has gradually elevated. Occasionally I will experience pain in my feet after walking.
“Upon reporting these experiences to my doctor, he has responded that I should just tolerate it because I need to lower my cholesterol. I feel like for years I have been falling down a rabbit hole. I feel trapped with no viable solution.”
Jean developed severe muscle complications while taking atorvastatin:
“I have necrotizing myositis, diagnosed by a muscle biopsy, triggered by atorvastatin. After 15 months and the failure of treatment with corticosteroids and rituximab, I have started infusions of immunoglobulin and methotrexate in tablet form.
“I am now so weak I cannot get up from most ordinary chairs or use a normal toilet. I cannot walk far and can only get up my stairs very slowly and with great effort. I cannot lift anything above my shoulders or from below my hip level. I cannot go for a walk or do my own shopping, and I can hardly get into and out from the car. Life has been wrecked by this. I am 59, and until this happened enjoyed hill walking and keeping my half acre garden.”
Kay’s husband now has diabetes:
“My husband has been on statins for 25 years and during this time has had multiple heart attacks and now has heart failure. Recently the doctor increased his atorvastatin dosage from 40 mg to 80 mg. Within a few weeks, his A1C rose from borderline into the diabetic range (7.1).”
Steve’s blood glucose went down while taking atorvastatin:
“I have had a different experience. After taking atorvastatin my sugar levels have actually decreased significantly. After having a heart attack, I was prescribed atorvastatin 40 mg. My fasting morning sugar level was usually between 140 and 180. It is now consistently 100 or less. Although I do spike after eating carbs, the readings go down pretty quickly.”
The Unpredictability of the Blood Pressure Drug Lisinopril:
Lisinopril is the most prescribed blood pressure medications in the US. At last count, 20 million Americans take this drug daily. For many, it controls hypertension very well. Others, however, experience the cough from hell!
Valerie had such a bad experience with lisinopril that she wants it banned:
“I was taking lisinopril for a while. I started coughing all day and all night. The cough got so bad I was urinating on myself. I was spitting mucus that was clear and bubbly. That went on for a long time. This medicine should be banned, and we all should be compensated for the agony that we experienced.”
DD is a pharmacist and did not realize that a life-threatening angioedema attack could be delayed for many years:
“I am a pharmacist and took lisinopril for over 12 years before I had an angioedema attack. About 8:00 PM I started having allergic symptoms and by 10:00 PM my face was swelling, and I was having trouble talking. I rushed to a hospital emergency room, fortunately only 2 miles away.
“I was immediately diagnosed as experiencing angioedema and admitted. Steroids started and about midnight I was well on the way to recovery. I spent the night in the ICU and was discharged about 11:00 the next morning. I had never thought that such a delayed (12 years) reaction could occur.”
Nancy’s husband has had no problems with lisinopril:
“My husband has been taking Lisinopril for years, but only 5 mg once daily. He has been fine with it so far.”
You can read more about the cough from hell at this link. Although many people can take lisinopril without problems, others can experience an uncontrollable cough, neck swelling, breathing problems or even abdominal angioedema (intestinal blockage). Predicting who who will experience such complications is virtually impossible.
What Are We to Make of the Unpredictability of Medications?
If there is any lesson to be learned from the stories above, it is that people can vary dramatically in their reactions to pharmaceuticals. Doctors and drug companies need to recognize that some people are more susceptible to side effects than others. We have just scratched the surface.
Some people love gabapentin to ease nerve pain, while others find it intolerable. Many people rely upon the antidepressant amitriptyline or the sleeping pill zolpidem to fall asleep. Others complain bitterly about the adverse reactions they experienced.
Final Words:
The old refrain, start low and go slow, might be a prudent way to begin taking any new prescriptions. Always ask your health care professional about the most common and the most serious side effects before starting a new prescription.
We have prepared a free form that will allow you to obtain crucial information before filling a prescription. You can download our free “Drug Safety Questionnaire + Medical History” form at this link. Your prescriber should take a few moments to fill it out before sending you off with a new prescription.
Have you ever experienced an unexpected complication from a medication or has your medicine worked really well with no side effects? Share your story in the comment section below. If you think this article is worth sharing with family or friends, please email it or blast it out on social media by scrolling to the top of the page and clicking on one of the icons in the upper left corner. Thank you for supporting our work.
