Key points

Introduction

In a world where medications are commonly requested by patients, concussion is one diagnosis where they are not commonly prescribed. Although clinicians hope to speed the process of recovery, to this date there is no medicine or supplement clinically proved to reliably improve concussion recovery times. However, there are recent and ongoing clinical trials of certain supplements that may provide an opportunity to minimize symptoms during recovery. Note that there are no medications that are US Food and Drug Administration approved specifically for the treatment of concussion, and any medications prescribed would be considered off-label use.

Over-the-counter supplements are typically readily available, have a favorable risk/benefit profile, and may be useful as an adjunctive treatment, particularly early in the concussion recovery course. Prescription medications more commonly carry the risk for more significant side effects and are instituted only when certain criteria are met, most commonly in the cases of prolonged recovery or heavy symptom burden without improvement with standard care.

Posttraumatic headaches are a common sequela of concussion, and headache is the most common symptom reported with concussion. Headaches may be persistent and episodically exacerbated by triggers commonly found in a student-athletes’ lives, including stress (cognitive or physical), light (including digital devices), noise, movement, and peripheral movement (eg, crowded cafeterias or being a passenger in a motor vehicle).

Most patients recover from concussion within a period of days to weeks, ^{, ,} but some patients (perhaps up to 15% ) still have symptoms beyond a 3-month period. ^,

Prescription medications are typically considered only if the duration of symptoms exceeds the typical expected recovery period, symptom burden is significantly affecting quality of life (eg, activities of daily living, such as school attendance and participation, sleep quality, or basic light noncontact exercise), and the potential benefits of the medication outweigh the risks. Medication therapy is not intended to return athletes to the playing field more quickly. If medication is initiated, the athlete should have successful resolution of all symptoms (as well as normalization of cognitive function and balance testing) during treatment and for a sustained amount of time after the withdrawal of the medication to be considered for potential return to contact sports. Of course, the prescribing clinician must be knowledgeable about the medication’s dosing schedule, side effect profile, interactions with other medications, and pretreatment testing that may be necessary for any prescription.

Clinicians have tended to group the most common symptoms of concussion into domains or symptom clusters. Most commonly, the symptoms are categorized as somatic (most commonly headache), sleep disturbances, emotional symptoms, and cognitive symptoms. ^,

Headaches

Headache is a common symptom after concussion. Interestingly, headaches are even more common after mild traumatic brain injury (TBI), such as concussion, compared with moderate and severe TBI. ^{, ,} Headaches may be described in several ways, including constant, episodic, band or tensionlike, or migrainous (eg, associated with light and noise sensitivity or nausea). They are often classified according to the International Headache Society classification system as a means to tailor treatment. Even in the setting of postconcussion syndrome, clinicians should be aware of the many other common causes of headaches, including dehydration, poor nutrition, decreased visual acuity, stress, allergies, and menstrual cycle. The original injury may also have had concomitant cervical myofascial injury (whiplash), or triggered neuropathic scalp pain, so the evaluation of the patient should always include palpation of the occipital, cervical, and periscapular areas to look for areas of tenderness, trigger points, or allodynia. These examinations may be opportunities to alleviate nonconcussion contributors to headache with physical therapy, massage, acupuncture, or, in rare cases, occipital nerve blocks.

The characteristics of a headache can help guide potential treatment options. Of patients with postconcussive headaches, a study showed that about half of the patients have migrainelike features, whereas 32% to 37% have characteristics of tension-type headache. Cervicogenic headache was third at around 4% and unclassified averaged around 11%. Many, including the American Medical Society of Sports Medicine (AMSSM), recommend that headaches be treated based on the characteristics and type of headache.

Most people with concussion self-treat their headaches with over-the-counter medications, including nonsteroidal antiinflammatory drugs (NSAIDs) and/or acetaminophen, regardless of the type of headache. However prolonged daily use of NSAIDs carries the potential risk of rebound headaches, which may complicate recovery. ^{, , ,}

NSAIDs and acetaminophen are used principally as an abortive treatment, but, for patients with daily disruptive headaches, a preventive medication may be warranted. For prevention of migrainelike postconcussive headaches, tricyclic antidepressants (TCAs) and antiepileptics are commonly used. ^{, ,}

For many years, amitriptyline (a TCA) has been a common option. Although the data are not universal, some retrospective studies have shown that up to 90% of patients achieve excellent or good recovery when treated with amitriptyline for posttraumatic headaches. It has been found to be helpful for migrainous and tension-type headaches. ^{, , ,} TCAs are typically prescribed at much lower doses compared with the levels needed for antidepressant treatment. This fact may be used as a clarification point for patients and families who may be shocked at the suggestion that an antidepressant may be prescribed for their child. It is also wise to obtain an electrocardiograph to confirm that the patient does not have prolonged-QT syndrome because TCAs can drive this condition into an arrhythmia. Among the most common side effects of amitriptyline and other TCAs is drowsiness, especially on initiation of treatment. For this reason, a TCA is typically dosed before bedtime, and it may have a particular advantage in those patients with both headache and insomnia. If daytime somnolence is particularly disruptive, nortriptyline could be considered as a potentially less sedating alternative to amitriptyline. Although less common than fatigue, all TCAs still carry the risk of increased emotionality, palpitations, or orthostasis. In our practice, we aim for the lowest effective dose between 10 mg and 50 mg, commonly starting at a low dose of 10 mg and, over several weeks, reassessing clinically to evaluate for tolerance and effectiveness.

Other classes of medications that have commonly been used include antiepileptics. Valproic acid seems to be an additional, relatively safe option for treatment of persistent headaches after trauma.

Topiramate is another viable option for postconcussive headache. As with all medications, providers should be aware of the side effect profile and be comfortable with prescribing these and titrating them to effect. Gabapentin has also been used frequently for prolonged headaches, particularly if there is clinical evidence of neuropathic scalp pain or allodynia, despite the fact that it lacks good evidence for its efficacy in treating migraines. Especially on initiation, this medicine can cause fatigue. Similar to some of the other medications, prescribers can use this to advantage by starting the medication at nighttime while the patient builds a tolerance to the side effects. Gabapentin has a large therapeutic window so it can be titrated to effect as long as the patient tolerates it. Also remember that, when it is time to stop this medication, a gradual tapering will help reduce potential withdrawal symptoms.

β-Blockers, most commonly propranolol, are another class of medications that are commonly used in migraine prophylaxis and may be considered in posttraumatic headache treatment when it is migraine type. ^{, , , , ,} As with the other medications, clinicians must be aware of the side effects of this drug. Avoid prescribing this medication in patients with asthma and low blood pressure, among other conditions, because of unfavorable beta-blockade side effects. In some patients, β-blockers can have an anxiolytic effect; however, they may also potentially exacerbate the symptoms of depression, which is a common comorbidity in patients with prolonged headache and postconcussion syndrome after minor TBI (mTBI). ^,

Sleep

Sleep patterns are commonly affected following concussion and disruptions in quality sleep can exacerbate symptoms of anxiety and mood. Sleep disruption itself can create most of the symptoms seen on the Postconcussion Symptom Scale, including fatigue, irritability, difficulty concentrating, difficulty remembering, not feeling right, and so forth. Ideally, restoring sleep patterns should be attempted without medication when possible. The first thing to address is sleep hygiene, which includes eliminating screen time in the evening before bedtime; sleeping in a dark, cool room; avoiding caffeine and alcohol consumption; minimizing daytime napping; reducing noise; and performing daily exercise. Sleep hygiene is key when working with postconcussive patients.

Melatonin levels, which naturally regulate the sleep/wake cycle in the brain, decrease in the setting of bright lights. Therefore, in postconcussive patients, suggestions include avoiding digital screens and dimming lights at least an hour before bedtime. TBI may alter melatonin levels, and late-night screen time may further exacerbate this phenomenon. ^{, ,} Naps are also common during the concussion recovery, especially when patients are particularly somnolent in the initial phase, or when they are out of their normal pattern of school attendance and sports or exercise during prolonged recovery. Care must be taken to avoid deconditioning and to maintain the circadian rhythm. Daytime naps should be brief and should be avoided if nighttime sleep has become interrupted. Allowing for some daily daytime sun exposure; light activity, including walking; and avoidance of daytime naps may help mitigate some of the nighttime insomnia that can come with circadian dysregulation.

After addressing sleep hygiene, nightly melatonin supplements are a common, safe recommendation to help reregulate the circadian rhythm. Melatonin is safe, available over the counter, and low cost. Interestingly, melatonin has not only been shown to improve sleep in patients with TBI but has improved cognition in animal TBI models. However, the application of melatonin as a cognitive therapy is far from being considered well established.

Some medications used for insomnia, such as benzodiazepines and atypical GABA (gamma-aminobutyric acid) agonists may have negative effects on cognition and judgment; therefore, they should be avoided in the setting of concussion recovery. ^, Cognitive behavior therapy has been beneficial in general cases of insomnia, with some small studies showing that it helps anxiety and depression in postconcussion patients.

Other symptoms

Following head injury, depression and other anxiety are potential comorbidities. ^, Unlike the paradoxic pattern with headaches, where headaches are often more disruptive in mTBI than in more severe trauma, these psychological conditions tend to be more common in severe injuries. The AMSSM recommends consideration of medications for mood disturbance only after 6 to 12 weeks of continued symptoms. It also endorses the role of cognitive-based therapy, in place of or in conjunction with medications. Furthermore, the AMSSM recommendations state that stimulants should not be used for acute attention problems acquired from a concussion, which are expected to be temporary. However, if a patient had a previously diagnosed attention disorder and was on a stimulant medication preinjury, we withhold these medications only during the acute phase (24–48 hours) while also recommending brief cognitive and exercise restrictions during that time. Withholding this medication for a prolonged period of time may make it difficult to identify the cause of any ongoing attention difficulties. At present, there seems to be no evidence-based reason for prolonged withholding of stimulant medications in the setting of concussion recovery.

There have been proposed medical treatments, including memantine, β-blockers, betahistine, and oxcarbazepine, for oculomotor and vestibular disorders that may occur after concussion. These medications are not routinely prescribed by providers managing concussions, but they may be considered by otolaryngology specialists, ocular specialists, or others with appropriate subspecialty experience.

Omega-3 fatty acids

Although there are no recommended medical treatments to prevent concussion or speed recovery from concussion, one supplement that seems to have the most promise may be omega-3 fatty acids. One particular omega-3 fatty acid, docosahexaenoic acid (DHA), has been a focus of research because it is the predominant omega-3 fatty acid found in the phospholipid membranes of neurons. ^, Following TBI, phospholipid membranes break down and DHA levels are altered. ^, In addition, DHA plays a role in the cellular signaling cascade helping to protect against cell death, ^{, ,} regulates neurotransmitter levels, and possesses antiinflammatory properties. Perhaps more importantly, there are several animal studies that investigated the benefit of omega-3 fatty acid supplementation in both preventing and treating concussion. ^, In humans, there are reports that DHA could improve cognition in patients with TBI, ^, and may even benefit others with attention-deficit/hyperactivity disorder or depression. The interest in using DHA in human patients with concussion has grown and this has led to a recent, small feasibility clinical trial that showed that 2000 mg of daily DHA may hasten recovery in the concussed pediatric population. Because of the promising results, a larger, multicenter clinical trial of DHA in concussions could lead to future recommendations in concussion recovery. Considered relatively safe, common side effects of taking DHA, or other fish oils, are generally benign and include fishlike breath, belches, looser stools, reflux, and nausea. Concerns raised about omega-3 fatty acids increasing bleeding risks were not supported in studies, including with patients already taking other antithrombotic medications.

Summary

The medications that are used in postconcussion syndrome are typically used to help manage or minimize disruptive symptoms while recovery proceeds. These medications are not routinely used in most patients with concussion, who recover within days to weeks. However, it is beneficial to be aware of medication options that may be used in athletes with prolonged concussion symptoms or for those that have symptom burdens that preclude entry into basic concussion protocols, such as school reentry and light noncontact exercise. Clinicians who manage concussions frequently should become familiar with the options that are being used and investigated. Medications and supplements remain a small part of the concussion treatment plan, which may include temporary academic adjustments, physical therapy, vestibular and ocular therapy, psychological support, and graded noncontact exercise.