OTC Analgesics Improve Concussion Outcomes

Use of over-the-counter (OTC) analgesics — including acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) — improves concussion symptoms and reduces recovery time in injured athletes, preliminary results of new research suggest.

The results are important because currently there are few treatments for concussion, study investigator Kyle Arnold, MD, University of Washington Medical Center, Seattle, told Medscape Medical News.

“There was always this assumption that taking over-the-counter analgesics might help with symptoms like headache, but we haven’t really asked that question before,” he added. However, Arnold cautioned these are early findings and need to be validated.

“This a very intriguing kind of first step in the process. If this is proven to be an effective treatment, analgesics are easily accessible and something that can be implemented pretty quickly,” he said.

The findings will be presented at the American Academy of Neurology 2025 Annual Meeting in April.

Reduced Inflammation

Research indicates that OTC analgesics help reduce neuroinflammation after traumatic brain injury (TBI). However, limited research has examined these medications’ impact on clinical outcomes after a concussion, which is classified as mild TBI.

The investigators used data from the National Collegiate Athletic Association (NCAA) and US Department of Defence CARE Consortium. The study included 1661 NCAA athletes and military cadets, mean age was about 18 years, and 45% were women.

Of these, 44% participated in contact sports and 13% in limited-contact sports. Among all contact sports, American football had the highest concussion rate, followed by soccer and other sports such as ice hockey, said Arnold.

Approximately 35% of study participants had a history of a previous concussion, and 6% had a history of migraine headache.

Researchers separated participants into those who used OTC analgesics post-injury (N = 813) and those who did not (N = 848). They categorized OTC analgesic types as acetaminophen and NSAIDs.

The researchers compared groups taking no analgesics, those taking acetaminophen (n = 600), those taking NSAIDs (n = 75), and those taking both types (n = 78) post-injury.

Using data provided by trainers working with the athletes, they determined concussion recovery time in days, measuring the period from injury to clearance for unrestricted return to play (URTP) and the time taken to becoming asymptomatic (daysASYMP).

Clearing an athlete to play after a concussion requires progressing through a structured protocol to assess fitness for return. In this study, researchers evaluated the time it took for athletes to reach 50% and 90% recovery after a concussion.

They also collected data on symptom and headache severity using the Sports Concussion Assessment Tool, Third Edition, a standardized assessment that measures self-reported concussion symptoms. These symptoms may include dizziness, memory issues, cognitive slowing, and headaches, said Arnold.

These measures were taken at baseline (preseason), immediately post-injury (< 1-day post-injury), and post-injury (median of 3 days post-injury). 

The study showed OTC analgesic use was associated with faster URTP (hazard ratio [HR], 0.796; 95% CI, 0.697-0.909; P < .001) and sooner daysASYMP (HR, 0.851; 95% CI, 0.744-0.972; P = .034).

Arnold noted the group that used OTC medications hit the threshold of 90% recovery about 7 days faster than those not using OTC medications.

Lower Symptom Severity

OTC use also led to lower post-injury symptom scores (logarithmic-transformed estimated mean difference, −0.957; 95% CI, −0.944 to −0.959; P < .001) and lower post-injury headache severity scores (−1.07; 95% CI, −1.06 to −1.08; P < .001).

Earlier OTC analgesic use after injury was associated with quicker URTP and daysASYMP (P < .001).

It’s likely best to take analgesics within a day of a concussion, as most inflammation occurs in the first 24 hours, said Arnold. “We think targeting that build-up of inflammation in the first 24-hour period is probably why it’s more effective to take these drugs earlier.”

There were no significant differences between OTC analgesic types on concussion recovery or symptom severity. “We thought NSAIDs would work better based on their mechanism of targeting and inhibiting the COX-2 [cyclooxygenase 2] enzyme more directly, but there was actually no difference between the NSAID group and the ibuprofen group in our study,” said Arnold.

Although acetaminophen agents may also inhibit COX enzymes to some extent, they’re primarily pain relievers, so it was interesting that they too eased concussion symptoms. “We’re not quite sure what to make of that, but it could be that just reducing the pain could be producing some of the benefit we’re seeing,” said Arnold.

Gender and age didn’t seem to significantly impact the results, although Arnold noted the study was small.

He would like to see outcomes analyzed further in a randomized trial that compares larger groups. He noted the groups in the present study are “pretty uneven,” with many more participants taking acetaminophen.

Future research could also look at “the best timing,” dosing, drug type, and duration of OTC analgesic use, said Arnold.

Meanwhile, he said, it’s too early to recommend across-the-board use of analgesics post-concussion. “More work needs to be done before we can make a recommendation like that.”

Unsurprising Findings

Asked to comment, Frank Conidi, MD, director of Florida Center for Headache and Sports Neurology, Port St. Lucie, Florida, co-chair of Florida High School Athletic Association Concussion Committee, Gainesville, Florida, and team neurologist at Florida Panthers of the National Hockey League, said the study results “aren’t overly surprising” given headache is the most common symptom of concussion and the symptom most amenable to treatment.

“A number of studies have demonstrated that the overwhelming headache phenotype in concussion is migraine or probable migraine” and a number of studies have shown early treatment of migraine “lowers the duration and the risk for headache chronification, where acute pain becomes chronic,” he said.

Conidi commented that the finding — participants who treated their headaches experienced reduced headache duration and a lower risk for chronicity — aligns with his own clinical experience.

“We are quite aggressive in treating headaches early, and we have noticed that a good number of our patients recover more quickly compared to the standard recovery time of 10-14 days,” he said.

Conidi said it would be interesting to see a further breakdown of results for participants who had preexisting migraine and those who didn’t.

The investigators and Conidi reported no relevant financial disclosures.

The study received support from t he NCAA, the US Department of Defense, and the University of Washington Institute of Translational Health Sciences.