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Pills for the Chill: Treatments for the Common Cold

By Katelyn Chen

You wake up one morning with a stuffy nose and itchy throat, a cough already on its way. After ruling out COVID-19 and going to the doctor for a strep test, you’re left with just one diagnosis. It’s the common cold—an affliction so widespread that the average adult will suffer the ailment two to three times a year and the average child five to seven. Maybe you’ll pick up some Theraflu Severe Cold Relief on your way home, given the sorry state of your respiratory system. Turn the box over to look at the Drug Facts section, and you’ll see your typical assortment of drugs: ibuprofen, dextromethorphan for cough suppressant, and phenylephrine for decongestant. 

Phenylephrine has made national news recently for being the subject of an FDA advisory panel where panelists including medical faculty, pharmacy experts, and health law experts unanimously agreed that the oral drug was ineffective—not harmful, but not giving the advertised or expected effect. The advisory panel’s recommendation will now be considered by the FDA in determining whether to issue a regulation on phenylephrine. If the FDA ultimately acts on this information, products like Advil Congestion Relief, Dayquil Cold and Flu Relief, and, yes, the Theraflu Severe Cold Relief you’ve just purchased, will need to be taken off shelves and reformulated. But researchers have been publishing articles on how oral phenylephrine isn’t working for decades. So, what kind of cold medicine can be trusted as backed up by research? 

Besides oral phenylephrine, there are a few other decongestants commonly found in cold medicine. Contrary to popular belief, nasal congestion is not the result of excess mucus, but instead due to inflamed blood vessels in the nose that swell and enlarge the surrounding tissue and obstruct the airway. The imidazoline family, including oxymetazoline found in Mucinex Nasal Spray and xylometazoline found in other over-the-counter sprays, work by constricting blood vessels in the nose to allow for increased airflow. According to a review published in Current Medical Research & Opinion, intranasal xylometazoline provided higher nasal airflow to patients than the placebo for up to ten hours and scored higher on subjective scores for congestion relief: for example, study participants were asked to rate their congestion over time. About 3.4% of patients had nosebleeds and 10 to 26% found blood in their mucus, which are expected adverse, yet non-severe, effects of both the common cold and imidazoline use. Oxymetazoline nasal spray has a similar mechanism and effect, with one study in Rhinology finding that it lowered nasal congestion for up to 12 hours by both patient-reported scores and nasal flow rate. However, researchers noted that there have not been many studies analyzing the decongestant efficacy of xylometazoline—nor oxymetazoline—despite its popularity. 

Another family of drugs targeting respiratory symptoms are antihistamines, which are meant to help with rhinorrhea, commonly known as a runny nose, and cough. They are typically taken for allergies, as well as the common cold. Antihistamines block the chemical signal of histamine, which is what causes an allergic reaction when the body encounters an allergen. First-generation antihistamines, like brands Vicks Nyquil and Benadryl, are considered “sedating” because they can cause drowsiness due to the drug crossing the blood-brain barrier. The barrier is composed of a layer of endothelial cells between blood vessels and the brain and regulates the movement of molecules between the two. It is key to maintaining homeostasis in the brain and preventing pathogens from reaching the central nervous system. On the other hand, second-generation antihistamines, like Claritin and Zyrtec, are “nonsedating,” as they do not cross the blood-brain barrier.

The results of first-generation antihistamine studies are heterogeneous, with some studies reporting that antihistamine monotherapy had no effect on cough relief or rhinorrhea compared to placebo, while other studies show possible benefits. For second-generation antihistamines, the few studies that have been conducted on their effectiveness against cold symptoms have not shown significant benefits. However, researchers note that histamine is not often found in the mucus of individuals with the common cold. Thus, the effectiveness of antihistamines on cold symptoms is likely due to their disruption of acetylcholine chemical signaling, which is involved with involuntary actions like mucus production, saliva production, and heart rate. Acetylcholine signaling disruption also causes the adverse effects associated with antihistamines, including dry mouth and drowsiness.

Headaches and joint pain are also frequent symptoms of the common cold. Painkillers are often taken for relief, the most common being non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen. NSAIDs are a family of drugs that includes ibuprofen, naproxen, and aspirin. Acetaminophen is widely known by the brand name Tylenol. Both types of painkillers inhibit an enzyme responsible for inflammation and can be used to treat pain and reduce fevers. In a review published in the Cochrane Database of Systematic Reviews, ibuprofen was proven to have a significant effect on reducing headaches, muscle pain, joint pain, and fevers. Although adverse effects were low, it was unclear whether there was any effect on sneezing, and no benefit was found for other respiratory symptoms. Interestingly, ibuprofen was found to be slightly more effective than acetaminophen for fevers in a study in British Medical Journal, but researchers cautioned against prescribing one over the other due to differences in side effects and the modesty of the increase in effectivity. 

While the above includes the most common store-bought cold medicine, chances are that you’ll be sipping on a mug of honey tea or a bowl of chicken noodle soup as well. These home remedies certainly provide comfort when recovering from a cold, but research has shown that some may actually improve symptoms. Honey, widely used to soothe sore throats, may reduce cough for upper respiratory tract infections including the common cold. A review by researchers at the University of Oxford found that honey improved the severity and frequency of coughs compared to “usual care,” which typically constituted cough syrup or diphenhydramine, often marketed as Benadryl. However, the studies did not come to a consensus on whether honey was more effective than placebo amongst the three studies that tested such a comparison. Products containing echinacea, or coneflower, have been used to treat colds since the 1800s, but studies are not consistent in the species or extraction technique used. A study in the Annals of Internal Medicine did not find that tablets containing echinacea extract improved illness severity compared to placebo tablets. Still, high variability in results may have occluded small benefits caused by the echinacea extract. 

Ultimately, the unfortunate truth is that there usually isn’t a clear “yes” or “no” as to which drugs work for the common cold. Using phenylephrine as an example, a team led by Randy Hatton at the University of Florida in 2007 found that when comparing studies examining the same FDA-approved dose of 10 milligrams, there was no consensus on whether oral phenylephrine was efficacious for that dosage. Across 11 studies looking at a wider range of doses, nearly half were conducted by the same laboratory—Elizabeth Biochemical—with their studies having overly positive results as opposed to studies done by other laboratories, which either found variable results or no benefit compared to placebo. The recent FDA advisory panel revisited the data used to make the original 1994 recommendation to recognize oral phenylephrine as generally safe and effective and found that most of the research did not control for bias and may have been influenced by corporate sponsorship, as was potentially the case with Elizabeth Biochemical. 

Aside from reporting bias and possible fraudulent results in pharmacological research, it is clear that there simply isn’t enough updated research on cold medicine. For example, the studies that fulfilled the 2007 review’s requirements of reporting on efficacy rather than safety were all dated from 1959 to 1975. The common cold is notoriously difficult to research, as it encompasses a breadth of pathogens including rhinoviruses and influenza. However, further research is necessary given how often people use medicine to treat cold and cold-like symptoms. While there will never be a magic bullet for colds, using what has worked best for you during previous bouts can be a good place to start. Combined with a greater depth of knowledge about what research says might work and what doesn’t, you’ll hopefully find a remedy that helps you spend fewer days sniffling in bed.