pain killers

Are Women More Sensitive to Pain? Hormones and Pain Killers

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Are women more sensitive to pain? The question has been bandied about for years. Study after study answers affirmatively. Yes, women are more sensitive to pain. Not only that, women experience more pain than men for similar injuries and require more pain medication to achieve the same level of relief. And oh, by the way, for some strange reason, women suffer from more abdominal pain than men.

The question itself is encumbered with an all-knowing cultural and political ennui that subsumes the very possibility of an accurate answer. Instead it directs us toward the expected, and ultimately, uninteresting psychosocial babble; of course, women are more sensitive to pain, let us simply count the ways. While it is true that women do indeed require more pain medication than men and suffer from more abdominal pain than men, it rarely seems to occur to those conducting this research to re-frame the question from the tacit approbation of female ‘sensitivity’ to why might women require more pain medications than men. What is it about the medication or the female physiology that renders pain medications insufficient in women. Well, let me count the ways.

Pain Medications Designed by Males, for Males, with Males

Exclusive of the pain medications discovered accidentally, like the early opium-based or morphine derivatives on which no research was ever conducted, most pain medications developed in the 20th century were never tested on women. Indeed, women were prohibited from being included in clinical trials until 1993-1998. (Instead, we simply gave women the meds and hoped for the best). Even post 1998 when the new regulations were implemented to permit women in clinical trials, there were no requirements for drug developers to analyze the data based on sex and determine if a particular medication worked better or worse in women or even if the medication had more or different adverse events for women. As a result, many researchers have noted that women suffer disproportionately more adverse events per capita than men and that those adverse events are often quantitatively more serious. For more details, see: Women in Clinical Trials – So That’s Why My Meds Don’t Work. 

Even in early medication development, the animal research, uses males to develop and test the efficacy of a particular medication. A recent report suggests that 79% of all animal studies published over a 10 year period in the journal Pain, were done on male rodents. Only 8% used both males and females and only 4% tested the response differences between males and females. As the comments in this pain post suggest, testing on female rodents is expensive and difficult because of the animal’s estrus cycle (menstrual cycle for humans) – e.g. the hormone changes are rapid and complicated. It’s much easier and less costly to measure in male rats.

I would argue, adverse events in human females are exponentially more costly and difficult than conducting the appropriate research early in development. However, with the exception of the class action fines that pharmaceutical companies pay, it is not often that the pharmaceutical company – the drug developers – must bear the brunt of the early research costs or even bulk of the adverse event costs. Rather, it is governmental agencies that fund early stage research and insurance companies, governmental and private, respectively, who pay for the negative outcomes. With this bit of a misalignment that means no one pays for or is accountable for, what perhaps, could be avoided, if funds were allocated in the earlier testing phases.

Given that so few pain medications were developed using females (rodent or human), it is entirely possible that many pain medications simply do not work as well or even by the same mechanisms in females versus males. There is some evidence that this is true. Researchers have noted that while standard morphine type medications (opioid agonists) don’t work as well in women as in men, other medications appear to work better, such as the opioid agonist-antagonist butorphanol or pentazocine – pain killers that work on different types of receptors and by different mechanisms.

Female Biochemistry, Pharmacokinetics and Pharmacodynamics

What is it about the female physiology that makes some medications less effective than when given to males?  Well, to state the obvious, females are genetically, physiologically, structurally and biochemically different than males. Why would anyone presuppose that placing a compound into two discretely different environments would exact the same response? And yet, that is exactly what we do.

Drug disposition is sex-specific. How a drug moves through the body (pharmacokinetics)and what effects it elicits (pharmacodynamics) are determined by number of factors, most of which differ significantly in males and females. In one of the better written reviews of Sex Differences in Drug Disposition, researchers note that even in the few studies with sex-analytics, it is clear that women process drugs differently than men.

  • Drug transit through the GI tract is considerably longer in women than men (91.7 hours versus 44.8 hours).
  • Bile acid composition is different and acidity levels are different
  • Women show a higher maximum dose and AUC 87% and 71% of the time
  • CYP enzymes (the enzymes that break down drugs in the liver) vary with some variants consistently increased and others decreased by sex.
  • Food by medication interactions vary directionally by sex – that is they are not consistent, some increase metabolism, some decrease metabolism
  • Sex differences in kidney function
  • Sex differences in liver function
  • Sex differences in pain and opioid receptor density and activity
  • Women exhibit different pharmacodynamic profiles for a wide array of drugs
  • Cycling hormones dynamically change drug metabolism (pharmacokinetics) and drug effects (pharmacodynamics); pregnancy hormones change these drug parameters even more radically

Bottom-line, women are different than men. Existing medications need to be tested in women to see which ones work and which ones don’t, and then, prescribed accordingly. New medications should be developed for these differences. (Imagine, a whole new market by simply recognizing the obvious differences in the population). For medications already in development, sex analytics must be conducted before the drug is released.

Are women more sensitive to pain? Probably not, but we have different types of pain (frequently, undiagnosed or misdiagnosed and chronic) and respond differently to pain medications than men.

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This article was published originally on Hormones Matter on June 27, 2013.

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Endometriosis and the Journey to Advocacy

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I will never forget the words the doctor in the ER said to me: “I will not support your habit and I will not prescribe you anything.” These words, so easily said, cut me like a knife. I was no stranger to being told that my endometriosis “shouldn’t cause so much pain”. Or being told I was “a girl who needed to get over it”. But that night changed everything for me.

Let’s go back a bit. My endometriosis journey started when I was 15. I didn’t know what it was that was causing this debilitating pain but I did know that it wasn’t normal. Luckily for me, I had parents who weren’t happy with the answers we were getting either. I can’t even count the number of ultrasounds and CT scans I had trying to diagnose something that no one could see through either of these methods. I was told that my symptoms didn’t make sense by a handful of gastrointestinal specialists and I was refused a referral to a gynecologist because I wasn’t sexually active and therefore “couldn’t possibly have anything wrong with [my] reproductive organs”.

It took me 10 years to finally get the referral I needed. Unfortunately, this is not at all uncommon when dealing with this disease. When I finally got in to see a gynecologist, she diagnosed me with endometriosis by nothing more than just hearing my symptoms. Five minutes after I entered the office, she was ready to send me out with a prescription for birth control pills that were supposed to save me from the pain. I expressed concern with this treatment because by this point I was well versed on how endometriosis was diagnosed and treated, and I knew that birth control pills didn’t treat the disease. I had a family history of blood clotting and was nervous about this potential course of treatment but I was brushed off as being nothing more than a girl who worried too much. At my insistence, I was given a requisition for blood work that had to be paid by myself. I happily did it and 72 hours later was called back in. It was found that I had a genetic blood clotting disorder and that prescription for hormonal birth control would have potentially killed me by causing a lethal blood clot.

I transferred to another gynecologist and again, here was someone who didn’t understand why I wanted a laparoscopy. At this point in my life, I was starting to believe that I perhaps was losing my mind. I needed to know for sure and so I demanded the surgery. On May 31, 2010, I had surgery and was confirmed to have endometriosis on my reproductive organs and bowels. I was relieved. At this point, I thought this was my ticket to real treatment and more answers but instead, I’m really no better off than I have been over the entire course of this disease. I still have severe pain way too often.

I was out one night at a movie with my husband. Afterwards, we were driving home and I was crying. My husband knows that this is a bad sign. I told him I couldn’t make it to our house and he needed to go to my parent’s house immediately (they lived nearby). I began vomiting from the pain. I collapsed on the bathroom floor and couldn’t move. My parents called an ambulance and I was rushed into the ER. Three paramedics were convinced there was something very wrong with me. After two doses of morphine and Gravol, I was still writhing in pain. I felt that as soon as I mentioned the fact that I had endometriosis, I was somewhat written off. This is when the doctor came in to accuse me of being a drug addict looking for a fix. I yelled. I screamed. I demanded treatment and I will never regret the things that I did to stand up for myself. The nurse taking care of me slid me a card for the patient advocate who I contacted the next day. Unfortunately, after a lengthy investigation, I was told by the hospital that the doctor was within his rights and was “trying to educate [me] on the pitfalls of drug abuse”.

It was after this night that I was determined to raise my voice. We need more awareness about this disease. We need doctors to become specialists in this area. We need better treatment. I started a local support group as a result because I don’t believe that anyone should experience something like this without having someone to turn to who truly understands. It has brought me great friends and amazing support – something anyone fighting this disease needs. My advice is simple: never stop fighting for yourself or fighting for awareness. This disease affects too many women for us to remain silent. I hope that my small piece in this world can make a difference for someone else.

If you have endometriosis or any other complex condition and would like to share your story on Hormones Matter, write for us.

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Prescription Medications While Pregnant

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A subject near and dear to my mom-scientist’s heart is the rapid increase and over-use of prescription medications during pregnancy. In the span of about 30 years, we’ve moved from a strong, and perhaps more medically prudent, tradition of no medication, no caffeine, no alcohol while pregnant, to 70–80% of women taking at least one prescription medication during pregnancy.

The Rise in Prescription Medications during Pregnancy

According a report by the CDC, between 1976-2008 prescription medication use during pregnancy grew at a staggering rate.

  • 60% increase in first trimester prescription medication use
  • The number of women taking >4 prescription medications while pregnant has tripled
  • The number of women taking anti-depressants while pregnant has increased significantly
  • 1 in 33 babies are born with birth defects

On average, American women are taking 2.3 medications during pregnancy and sometimes more. I cannot help but wondering when we became so unhealthy.

Prescription Opiates during Pregnancy

More recently, a study published in the Journal of the American Medical Association estimated that 13,500 babies are born every year with Neonatal Abstinence Syndrome or NAS. NAS is a polite way of describing children who are born addicted to the pain killers that were, at least originally, prescribed by physicians to their pregnant mothers. Infants who, in their first moments of life outside the womb, must endure the suffering of opiate withdrawal.

Anti-depressants during Pregnancy

A similar abstinence syndrome is observed in infants born to women taking prescribed selective serotonin uptake inhibitor (SSRI) anti-depressants. It’s called newborn behavioral syndrome, another overly benign name that describes the tremors, agitation, excessive crying, respiratory difficulties, and seizures that emerge post birth as an infant withdraws from SSRIs. This is addition to the increased risk of congenital heart malformations, Long QT syndrome and Persistent Pulmonary Hypertension, that are associated with SSRI infants.

Take Back Pregnancy

Much of this increase can be attributed to the brilliance of pharma’s mega-marketing machine, but the culpability for the consequences lay with us. Women make 80% of all family medical decisions.  We are the deciders for health. We have bought into the notion that a pill cures what ails us. Sometimes it is true. Often times is it not. It is incumbent upon us to know the difference, especially during pregnancy. Many women do not realize that:

Medications do not metabolize the same way in a pregnant versus non-pregnant woman

Most medications cross the placental barrier

Drug testing is not done on pregnant women

So we often have no idea what works, does not work and what the true risk and severity of the side effects will be until after the medication hits the market. Even then, the true risks are difficult to discern because of the glut of medical marketing that often discredits the early reports.

Marketing Prescription Medications to Physicians and Consumers

Just because a medication is prescribed by a physician or it can be purchased over-the-counter, does not make it safe. All medications have side-effects and most of those are not well-understood during pregnancy.  In the case of anti-depressants during pregnancy, study after study, after study, after study (here, here, here) has been published showing the adverse effects of these medications during pregnancy. Indeed, another two were published just recently, linking anti-depressants to pre-term birth and infant convulsions. And yet, the conventional wisdom has been, and is still, that treating depression during pregnancy pharmacologically will improve pregnancy outcome.

Depression treatment during pregnancy is essential. If you have untreated depression, you might not have the energy to take good care of yourself. You might not seek optimal prenatal care or eat the healthy foods your baby needs to thrive. You might turn to smoking or drinking alcohol. The result could be premature birth, low birth weight or other problems for the baby — and an increased risk of postpartum depression for you, as well as difficulty bonding with the baby.”

The data have not born that out. Even the FDA , though they acknowledge the serious adverse events associated with SSRIs during pregnancy,

FDA Drug Safety Communication: Selective serotonin reuptake inhibitor (SSRI) anti-depressant use during pregnancy and reports of a rare heart and lung condition in newborn babies.”

they recommend no changes in prescribing practices.

“At this time, FDA advises health care professionals not to alter their current clinical practice of treating depression during pregnancy. Healthcare professionals should report any adverse events involving SSRIs to the FDA MedWatch Program.”

What is a Girl to Do?

Learn a little chemistry, understand basic statistics, read and research every medication you take, even when you are not pregnant, but especially when you are, and most importantly, make educated choices about your health, your child’s health and the health of your family.

This article was published originally on Hormones Matter in September of 2012. I am sad to say, the problem has only become worse.

 

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Women in Pain: Problems and Mistreatment

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Chronic pain in North America is a major problem for men and women alike, affecting about one-third of adults. Many people of both genders do not receive adequate treatment for their pain. This causes great personal suffering, as well as high costs to the economy through direct health care costs and loss of work productivity for those in pain. However, women with pain face additional problems that suggests there is a systematic bias in the way healthcare is delivered to women. Diseases that affect mostly women are generally poorly understood and understudied, and although women report pain that is more frequent, more severe, and of longer duration than men, in general women’s pain is treated much less aggressively.

Women are at higher risk of developing a chronic pain condition than men. For example, women have triple the risk of autoimmune diseases, which are often associated with chronic pain, compared to men. Women also suffer from certain painful diseases that are rare in men, such as endometriosis and vulvodynia. Endometriosis alone affects one in ten women, and women who have endometriosis often have other painful diseases as well, such as interstitial cystitis/painful bladder syndrome.

However, research into causes and treatments for these diseases that disproportionately affect women is sadly lacking. A report written by the Campaign to End Chronic Pain in Women looked at six conditions common in women that are routinely misdiagnosed and ineffectively treated: endometriosis, vulvodynia, chronic fatigue syndrome, fibromyalgia, interstitial cystitis/painful bladder syndrome, and temporomandibular (TMJ) disorders. Examining funding to these six conditions by the National Institutes of Health (NIH) revealed that on average, the NIH spends $1.33 per affected patient on research into these conditions, compared to $186 per patient for Parkinsons’s disease, or $53 per patient for diabetes.

However, one need not look at diseases that are underfunded, poorly understood, and lacking effective treatments to find evidence of a gender bias in medicine. One of the best examples of gender bias is, surprisingly, in coronary heart disease. When presenting to emergency rooms or hospitalized for a heart attack, multiple studies have shown that men receive faster access to diagnostic tests and treatments, and men are more likely to receive advanced procedures and better care (for example,see here, here, here and here), and these disparities have not changed over time.

Although heart disease can present differently in men and women, atypical presentation in women does not account for all of the difference in delayed or lack of access to tests and treatments. In one study of doctors evaluating hypothetical patients— male patients and female patients presenting with typical heart attack symptoms and identical risk factors– the doctors did not make different recommendations for the male and female patients. However, when stress was included as a risk factor, only 15 percent of doctors diagnosed heart disease in the women, compared to 56 percent for the men. This study suggests that doctors are much more likely to write symptoms off as psychological when the patient is a woman. And women are medicated as if their pain is emotional instead of physical: for example, after coronary artery bypass graft surgery, women are less likely than men to receive opioid pain medication, and more likely to receive sedatives instead.

Many studies have shown that female gender is a major risk factor for the undertreatment of pain, across many different types of pain. After abdominal surgery and appendectomies, women receive less pain medication than men, even though many studies have shown that women are more likely to report higher levels of pain than men. For cancer pain, and pain caused by HIV, women are significantly more likely to be undertreated for pain. Even paramedics are more likely to give opioid analgesics to men suffering from pain pre-hospital admission than to women. In general, doctors and other medical professionals are more likely to view women’s pain as caused by emotional factors even in the presence of positive test results, and are more likely to administer tranquilizers, antidepressants, and non-opioid analgesics to treat women’s pain.

Women face obstacles to getting appropriate care for many different diseases, at every step of the process. Women’s diseases tend to be underfunded, underresearched, and poorly understood, so getting a diagnosis is difficult, especially when there is the additional obstacle of health care providers tending to assume that women’s symptoms are psychosomatic. Once diagnosed, women do not receive the same level of care for their diseases that men do. And if women can be shortchanged on care for cardiac conditions, which tend to be taken seriously in our society, well researched, and have evidence-based guidelines to guide treatment, imagine how poorly women may be treated for diseases like endometriosis, for which myths about causes and effective treatment abound, and their pain cannot be measured with any objective tests.

Until medical care for women’s diseases moves from the 1950s into the present day, the only solution for women is to be extremely persistent. Women need to seek out the few care providers who understand their disease and are up to date on the latest, albeit sparse, research, and they need to be persistent about having their symptoms acknowledged and treated by their care providers. And in general, we need to keep pushing for better awareness of these problems, and funding for research so that women can receive the medical care they deserve.

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Hypersensitivity to pain, my ass!

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A multitude of reports have emerged in recent years denoting the over use of pain killers and other medications. With narcotic pain killers, in particular, data suggest a four-fold increase in opioid use since 1999, and over 100,000 deaths by opioid overdose during same time period. The data also indicate a close correspondence between the increase in prescriptions for pain killers and pharma sponsored marketing, ‘research’ and policy changes that have inculcated medical agency guidelines over the last decade.

For women, this is a particularly troubling trend, as other research indicates we are the primary targets of narcotic prescribing; women take 50% more pain killers than men. We also take 36% more medications than men in general. Speculation about why women take more pain killers than men, often involves psychosocial characteristics including a reduced sensitivity to pain, a predisposition to pain causing diseases, and a predilection to report the pain to one’s physician. Women seek out medical treatment at a much higher rate than men.

What often fails to get mentioned is that:

  1. Pain medications don’t work  as well in women because as we’ve reported before few females, rodents or otherwise, are used in the development of these medications.
  2. Even when female animals or women are used in drug development research, cycling hormones are not analyzed as factors in the effectiveness of the medication.
  3. For the myriad of pain related disorders affecting women, many lack evidence-based diagnostic criteria (less than 30% of Ob/Gyn practice guidelines are based on actual evidence) and frequently physicians and the lack of effective diagnostic criteria hastens many to presume an underlying psychosocial or mental health issue.

I personally think the psychosocial arguments that women are more sensitive to pain than men are nonsense. Rather, I think there is a lot more inherent to our physiology that makes pain related conditions not only more likely, but more difficult to treat.

Consider for example, the menstrual cycle and childbirth. These amazingly complex, biochemically radical, pain-inducing, often life-altering experiences are just a ‘normal’ part of female existence. I dare any man to experience the exponential and repeated cyclic change in biochemistry, akin to a repeated drug addiction and withdrawal pattern, that is the female menstrual cycle. The myth of female hypersensitivity to pain, based largely upon the ineffectiveness of pain or medications that were never designed for her changing biochemistry, is just that, a myth. And though I do admit, some humans are more sensitive to pain than others, the contrived experimental methods that designate women as hyper-sensitive do great damage to our understanding of women’s health and the differing pharmacokinetics across the menstrual cycle, pregnancy, postpartum or menopause.

And then of course, there is endometrial sloughing, necessitating a cramping mechanism to propel the tissue outward or the grandmother of all pain experience, childbirth where women deliver 8lb humans through a cavity opening that expands only to 10 centimeters, often times choosing to not utilize pain medications. These ‘normal’ events of a woman’s life are not indicative of a ‘hypersensitivity to pain’.

No, I don’t buy this mumbo jumbo that women are somehow more sensitive to pain than men. If anything, most women have a higher tolerance to everyday pain than most men. But there is a rationale to perpetuating this myth; it limits innovation in women’s health.

Why innovate when a company can make billions prescribing the same old medications at higher and higher dosages, to more and more people? Why address the needs of half the population, when one can blanket the market with drugs for the entire population?  And to that point, why develop more accurate diagnostic criteria or more effective medications for conditions that only effect a small subset of the total population; especially when medications developed over 50 years ago can be used?  If these medications are addictive, have side effects that necessitate other medications and are extremely difficult to withdraw from, well then, those are just added bonuses. It’s a wonderful business model, albeit a little less than ethical.

Despite the obvious marketing excess, we as consumers bear as much responsibility for the increase in narcotic prescriptions as does the pharmaceutical industry. We are letting this happen. Let’s face it, it is much easier to take a pill to make the pain go away (or eat a pint of ice cream to alleviate stress) than go after the root problem. It is difficult to address root causes. It is especially difficult if one is suffering from a medical condition that is chronic, pain-inducing, poorly understood, not easily diagnosed, and for which there are no effective medications. Women disproportionately suffer from these types of conditions – think fibromyalgia, endometriosis or even migraines.  We also make 80% of all family medical decisions. So ladies, we need to stand up and begin educating ourselves and our families about health and disease. We must demand more research and we will probably have to lead it ourselves.

 

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Over-The-Counter Painkillers: Use Medications with Caution

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The over-the-counter (OTC) medications acetaminophen (Tylenol) and ibuprofen (Advil, Motrin) are used by millions of people every day, for common conditions such as headaches, fever, muscle pain, chronic pain conditions, and arthritis. Yet how many people are aware that they can cause serious side effects, and in the most severe cases, death? Because these medications are available over the counter in drugstores and are taken by many people without any discussion with a doctor or pharmacist, the risks may not be well understood.

Medications with Acetaminophen

Acetaminophen is the leading cause of acute liver failure in the U.S., a serious and sometimes fatal condition which in some cases can necessitate liver transplant. Many cases of acute liver failure are caused by acetaminophen overdose; however, half of overdose cases are unintentional. In many cases of unintentional overdose, patients took more than one medication containing acetaminophen without realizing that both medications contained it. Acetaminophen is present in many medications, both prescription and non-prescription. Combination products that have acetaminophen as an ingredient include:

  • Prescription painkillers such as Darvocet, Percocet, Lortab,  Ultracet, and Tramacet
  • OTC cold and flu medications such as Actifed, Dayquil, Dristan, Nyquil, Sudafed, and Theraflu
  • Headache medications such as Excedrin

There is also some concern about the safety of acetaminophen at label-recommended doses, especially in patients at higher risk of liver injury from alcohol consumption. Acetaminophen at therapeutic doses may exacerbate the effects of liver injury from other causes. Individuals who are at higher risk of liver injury, such as those who consume more than three drinks of alcohol daily, are severely malnourished, or who take medications that induce liver enzymes, need to be aware of the potential risk of taking acetaminophen.

FDA and the Acetaminophen Medications

Because of these facts, in January 2011, the FDA announced new measures to reduce the risk of severe liver injury with acetaminophen-containing medications. Manufacturers are required, by 2014, to reduce the amount of acetaminophen in any combination product to 325 mg, in order to reduce the risk of accidental overdose when multiple acetaminophen-containing products are taken together. The FDA also requires a boxed warning on the package inserts of acetaminophen products highlighting the risks of liver injury, and the fact that concurrent alcohol consumption has been identified as a risk factor. Further, pharmaceutical manufacturers in the U.S. have lowered the recommended daily maximum dose on the labels of OTC acetaminophen products from 4000 mg to 3000 mg.

In addition to the liver injury risks, acetaminophen is also associated with rare but serious skin reactions. These skin reactions, known as Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP), can be fatal. Reactions can occur with the first use of acetaminophen, or any time it is being taken. The FDA has issued a warning to consumers about these reactions, and will require that a warning be added to the labels of prescription acetaminophen-containing products.

Medications with Ibuprofen

Ibuprofen is another common OTC medication that can have serious side effects. Ibuprofen is a type of non-steroidal anti-inflammatory (NSAID): medications of this type are very commonly used for chronic pain syndromes and arthritis, with more than 70 million prescriptions and 30 billion OTC tablets sold annually in the U.S.  Prescription NSAIDs include celecoxib, diclofenac, indomethacin, mefenamic acid, meloxicam,  and naproxen (Celebrex, Voltaren, Indocin, Ponstel, Mobic, and Anaprox), and OTC NSAIDs include ibuprofen (Motrin, Advil) and naproxen (Aleve).

NSAIDs as a group (prescription and OTC) are generally well tolerated, but their use can increase the chance of a heart attack or stroke that can lead to death. Individual NSAIDs have different cardiovascular risk profiles. The highest risk is with the newer class of NSAIDs called COX-2 inhibitors, which include celecoxib, rofecoxib, and valdecoxib (Celebrex, Vioxx, and Bextra). In fact, rofecoxib and valdecoxib were taken off the market due to concerns over their cardiovascular safety: clinical studies had shown an increase in the risk of heart attack and death. The traditional NSAID diclofenac also has an increased risk of cardiovascular morbidity and death, similar to the COX-2 inhibitors. The safest alternatives with respect to cardiovascular risk are ibuprofen in OTC doses (less than 1200 mg per day total) and naproxen. The risk of cardiovascular morbidity increases with increasing dose and duration of use.

In addition, NSAIDs can cause adverse gastrointestinal events such as ulcers, and bleeding in the stomach and intestines, which can occur at any time during treatment. Gastrointestinal complications can range from mild, such as indigestion, to severe, such as ulcer-related perforation, obstruction, or hemorrhage. Mild gastrointestinal adverse events such as nausea, heartburn, dyspepsia, and abdominal pain are extremely common and may occur in up to 40% patients taking NSAIDs regularly. Serious complications, although much more rare, are still too common, and their incidence has not changed in the last decade. For example, in patients taking NSAIDs for arthritis, the annual number of hospitalizations for serious gastrointestinal complications is estimated to be about 100,000, with over 16,000 deaths.

Almost 75 percent of patients who used NSAIDs regularly were either unaware or unconcerned about possible gastrointestinal complications, and two-thirds of patients stated that they expected warning signs before developing serious complications. However, only a minority of patients with serious gastrointestinal complications due to NSAIDs had gastrointestinal complaints prior to the serious complication.  Risk factors for adverse gastrointestinal events include advanced age, higher doses of NSAIDs, a history of gastroduodenal ulcer or gastrointestinal bleeding, concomitant use of corticosteroids or anticoagulants, and serious coexisting conditions.

Although risks of ibuprofen at OTC doses have not been as well studied as prescription NSAIDs, or NSAIDs as a group, the same risks are definitely present when taking OTC ibuprofen. The risk of an adverse event increases with increasing dose of ibuprofen, and for heart disease, the risk also increases with longer duration of use. Many users of ibuprofen may exceed the label-recommended dose in an attempt at better pain relief, or combine ibuprofen with other NSAIDs, both of which would increase the risk of adverse events. The label-recommended dose of OTC ibuprofen is 400 mg per dose, up to 1200 mg per day. However, in my own experience I have been advised by multiple doctors to take 600 to 800 mg per dose, up to 3200 mg per day, without any discussion of the potential for adverse events. Not surprisingly, I have NSAID-related gastritis. I have also talked to many chronic pain patients who routinely exceed the label-recommended doses of both ibuprofen and acetaminophen, and combine these medications with other prescription pain medications containing NSAIDs or acetaminophen. Although this might be acceptable for some patients, in some circumstances, it should definitely not be done without a physician’s recommendation and discussion of possible side effects.

Bottom Line with OTC Painkillers

The bottom line is that although acetaminophen and ibuprofen are generally well-tolerated at OTC dosages, especially for short durations of use, the potential for serious side effects exists. Just because a medication is available without a prescription doesn’t mean it is safe to use in all circumstances. Patients should be aware of the potential risks of these medications, and discuss their use, both in duration, and dosage, with their physicians. In addition, individual patients may have relevant medical history or concomitant medication use that puts them at higher risk of an adverse event, even with OTC medications, another reason to discuss their use with a physician.

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