The Influence of Migraine on Driving: Current Understanding, Future Directions, and Potential Implications of Findings.

OBJECTIVE: To review the published findings relevant to migraine and driving performance, with an intent to encourage discussion on research which may broaden understanding in this area and help educate healthcare providers and their patients.
BACKGROUND: Motor vehicle crashes result in more than 35,000 deaths and more than 2 million injuries annually in the United States. Migraine is one of the most prevalent diseases in the world, and many symptoms associated with migraine attacks have the potential to negatively influence driving ability.
METHODS: We reviewed the published findings related to migraine and driving performance. Study findings relevant to symptoms of migraine and their potential effect on driving were also reviewed. This required a more expansive exploration of the literature beyond migraine, for example, review of the literature relating to the effect of pain, sleepiness, visual disturbances, or vertigo on driving. Finally, the potential effects of treatment for migraine on driving were reviewed.
RESULTS: Literature on the effect of migraine on driving performance is sparse and, in general published studies on the topic have a number of limitations. Based on review of the literature pertaining to other disorders, it seems feasible that some symptoms occurring as part of the migraine attack could impact driving performance, although formal study in this area is lacking. Many of the approved treatments for migraine have the potential to impact driving, yet this has not been specifically studied, and the extent to which these risks are communicated to patients is not clear.
CONCLUSION: The impact of migraine on driving performance has been largely neglected, with few studies specifically designed to address the topic, and relevant studies were generally small with limited control of confounders. This area requires more focus, given a potential for impact on road safety.

calcitonin gene‐related peptide

central nervous system

Food and Drug Administration

motor vehicle crash

nonsteroidal anti‐inflammatory drug

tricyclic antidepressant

United States Prescribing Information

Introduction

Motor vehicle crashes (MVCs) are responsible for more than 35,000 deaths and more than 2 million injuries annually in the United States, resulting in an economic loss of hundreds of billions of dollars.1, 2, 3 Given the central role of driving in maintaining independence and empowering personal autonomy, better understanding of factors contributing to MVCs and the severity of associated injuries is paramount. Increased awareness, improvements in vehicular design, and legislative focus on speeding, seat belt use, and driving while intoxicated have reduced the number and severity of accidents in many parts of the developed world. Since operating a motor vehicle involves a wide range of cognitive, perceptual, and motor activities, focus has now shifted to initiatives that reduce individual driving impairment associated with distracted driving, as well as that associated with certain medical conditions, most notably epilepsy,4, 5 diabetes,6 sleep disorders,7 pain,8, 9 dementia,10, 11 and use of drugs (both illicit and prescribed).12, 13, 14

Migraine is one of the most prevalent diseases in the world, affecting over 30 million adults in the United States.15 Based on the most recent analysis from the World Health Organization Global Burden of Disease, it was the second largest cause of years lost to disability.16 It is a neurologic disorder characterized by episodic attacks of moderate to severe head pain and other symptoms.17, 18, 19 A migraine attack can begin with premonitory (prodromal) symptoms occurring hours or days before the onset of pain, with symptoms including yawning, tiredness, fatigue, changes in mood, impaired concentration, photophobia/phonophobia, and neck stiffness. The headache phase characteristically lasts 4‐72 hours with head and neck pain, as well as other associated symptoms, including photophobia, phonophobia, nausea, and dizziness or vertigo. A postdromal phase follows and usually lasts less than 12 hours. The most common postdromal symptoms include asthenia, fatigue, somnolence, difficulty with concentration, photophobia, and irritability. In about a third of people with migraine, reversible neurological symptoms (migraine aura) can occur before the onset, during, or in the absence of pain. Migraine with aura is characterized by visual, sensory, or speech/language disturbances in addition to the pain and other associated symptoms of migraine. Vestibular migraine, occurring in a small subset of those with migraine, is associated with moderate or severe vestibular symptoms including spontaneous, positional, and head motion‐ or visually‐induced vertigo.20, 21 Many of the symptoms associated with a migraine attack have the potential to negatively influence driving ability.

For a more complete understanding of any influence of migraine on driving ability, the effects of migraine treatments must be considered. A Food and Drug Administration (FDA) guidance document, available in draft form in 2015 and issued in 2017, outlines the circumstances under which drug developers need to assess drug effects on driving ability during development of a new treatment.22 Acute treatments for migraine in current use were approved prior to the issuance of this guidance document. As a result, they have not been subject to a thorough assessment of their impact on driving; any driving warnings in the United States Prescribing Information (USPI) appear to be the result of adverse event findings (eg, fatigue, dizziness) that could potentially affect driving and other activities.

Individuals with migraine have reported concerns about driving during an attack. A Canadian population survey reported that 45% of patients with migraine or tension headache worry about driving because of headache.23 In a cross‐sectional study of 1200 Spanish drivers questioned about their health, psychosocial characteristics, and driving, 63% considered headaches or migraine to impair driving performance “a lot” (vs “little” or “not at all”).24

We reviewed the published findings related to migraine and driving performance, as well as literature relevant to symptoms of migraine and their potential effect on driving. In the latter case, more expansive exploration of the literature beyond migraine was required. Finally, we reviewed published findings on the potential effects of treatment for migraine on driving. Throughout this review, we use the terminology motor vehicle crash (MVC) to cover the individual vehicular collision terms used in the various publications cited; these terms included motor vehicle accident, motor vehicle crash, motor vehicle collision, vehicular crash, vehicular accident, road traffic accident, and motor vehicle injury. The intent of this review is to encourage discussions and research that could broaden understanding in this area and, ultimately, help patients manage their disease, treatment, and activities accordingly.

Effect of Migraine on Driving Performance – A Review of the Literature

Effect of Migraine Disorder on Driving Performance

Published epidemiological data that address the effect of a diagnosis of migraine (regardless of whether the individual is experiencing a migraine attack) on driving performance are limited. Findings from population studies in New Zealand and Canada both suggest that having a diagnosis of migraine is associated with greater risk for injury from MVCs. In New Zealand, among 10,289 individuals enrolled in a prospective observational study of risk factors for serious injury and chronic disease and for whom relevant information was available, among those who reported a history of treated migraine, 18% reported a MVC compared with 10% of those who reported no history of treated migraine (P < .0001).25 A longitudinal, prospective dataset from the Canadian National Population Health Survey was used to examine the effects of medical conditions and medication use on subsequent MVCs.26 A significantly higher proportion of respondents with migraine reported subsequent a  MVC compared with those without migraine (n = 60 [12%] vs n = 861 [7%], P < .0001); significant differences in the proportion reporting a MVC were also seen in the case of the presence/absence of asthma, back problems, or distress but not in the case of presence/absence of arthritis/rheumatism, high blood pressure, or diabetes. Neither of these studies included information on the timing of the MVC in relation to the migraine attack or treatment.

In a study to evaluate the burden of migraine, 102 consecutively enrolled patients with migraine (with or without aura) and with ≤15 headache days/month were enrolled at a headache center in Italy. Patients reported function and disability over the past month, using a model endorsed by the International Classification of Functioning Disability and Health.27 About 20% of patients reported being severely limited in driving due to migraine, and about 15% communicated that they had severe issues with driving performance. No further details on driving performance were reported, nor was information available on healthy controls (ie, no individuals without migraine).

In a cross‐sectional hospital‐based study in the United Arab Emirates, investigators assessed the association between migraine and MVCs. Of 1985 consecutive vehicle drivers seen for accidents and trauma in an Accident and Emergency Department, 1715 consented to participate, of which 80 were diagnosed with migraine based on clinical interview.28 There was a significantly higher risk of careless driving and property damage in those with migraine vs controls, while risks of excessive speed violations, traffic violations, alcohol and drug use, or road traffic accident were not increased.

In a study of Israel Defense Forces professional male drivers (1300 involved in prior MVCs; 4305 not involved), findings from a multivariate analysis to identify health parameters associated with MVCs suggested that migraine increased this risk, as did valvular heart disease and perianal disease.29

While these studies provide a valuable contribution to the literature, there are study limitations. Sample sizes were often small; migraine was defined based on self‐reporting in some cases; and migraine cases were defined as individuals with migraine and not individuals who experienced a migraine attack while driving. The possibility of confounding factors was not thoroughly addressed and any identified association between migraine and driving impairment or accident risk does not equate to causality. For example, sleepiness or alcohol may be a trigger for a migraine attack but may also independently contribute to impaired driving. The potential effects of migraine treatment were not addressed. As will be discussed in more detail below, this is an important consideration given the recognized side effects of acute and preventive treatments for migraine.

In conclusion, migraine has been associated with impaired driving performance and MVCs but the few studies published have a number of limitations. To explore the effect of migraine on driving performance further, we reviewed the available data pertaining to commonly experienced symptoms of a migraine attack and their potential influence on driving performance.

Impact of Migraine Symptoms on Driving Performance

In this section, we focus on the symptoms of a migraine attack with potential to affect driving performance. These include pain, cognitive impairment, sleepiness, dizziness and vertigo, as well as visual disturbances (not necessarily independent of each other).

In migraine specifically, both head and neck pain are common symptoms in both the premonitory and pain phases of a migraine attack,17, 30 and there is potential for neck pain to limit neck movement while driving. Pain can affect physical function and has been associated with impaired cognitive performance in relation to attention, reaction time, and executive function.8 In a small study (N = 28), highway driving performance, assessed using a standardized on‐the‐road driving test, was impaired in patients with chronic pain (mostly related to lower back) vs controls, although patients with chronic pain rated their own driving quality to be normal.31 In a mail questionnaire study of 223 patients seen at a chronic pain rehabilitation center, 70% indicated that pain limited their driving in some manner.9

Cognitive dysfunction, whether a result of pain or arising as an independent symptom, is a common complaint of individuals with migraine, and deficits in attention, executive function, memory, processing speed, cognitive efficiency, and reaction time have all been reported.32, 33, 34, 35, 36 Individuals with vestibular migraine may have more pronounced cognitive impairment than those with a non‐vestibular migraine.37 Cognitive symptoms can occur during any phase of a migraine attack, and some individuals with migraine also complain of cognitive symptoms outside migraine attacks.36 Interictal cognitive dysfunction may reflect a prolonged postdrome, effects of preventive migraine medications, or cogniphobia (the specific fear and avoidance of cognitive exertion because the individual believes that it will precipitate or exacerbate a headache).38

Migraine can be associated with symptoms of tiredness, fatigue, and somnolence during premonitory and postdromal phases, and sleep disturbance is one of the most common triggers for migraine.39, 40 Sleepiness or drowsiness can result in cognitive impairment, including reduced vigilance and focus, delayed reaction time, memory impairment, poor coordination, and slowed information processing and decision making. The association between sleepiness and road traffic accidents has been well documented.41, 42, 43, 44 In 2017 alone, there were 91,000 MVCs and 795 deaths attributed to drowsy driving.45 The U.S. National Highway Traffic and Safety Administration is working with a number of Federal agencies, including the Centers for Disease Control and Prevention and the National Institutes, to raise public awareness about the risks of drowsy driving.

Dizziness, a nonspecific term, includes a sensation of imbalance, unsteadiness, lightheadedness, and vertigo (the illusion of movement). A migraine attack can be accompanied by one or more of these symptoms. Cohen et al46 compared self‐reported driving experience in individuals with various vestibular disorders (individuals with vestibular migraine were not included) to that in subjects without vestibular disorders (169 individuals in total). In general, individuals with vestibular disorders were aware that their driving performance was not optimal; they drove less and remained in their immediate neighborhood more so than healthy controls. Although some were advised by their physicians not to drive, they continued to drive, usually because they did not have alternative means of transportation. Individuals with a vestibular disorder had difficulty driving under conditions where useful visual cues were reduced, precise spatial navigation skills were needed, and rapid head movements were elicited, and they reported having to pull off the road due to vertigo in some cases. In an analysis of data from the 2001‐2004 National Health and Nutrition Examination Survey study, Wei et al47 evaluated the influence of vestibular dysfunction on driving difficulty in Americans aged ≥50 years (N = 3071). They found that vestibular dysfunction was associated with self‐reported driving difficulty; those with clinically symptomatic (vs self‐reported) vestibular dysfunction had a 4‐fold increase in odds of reporting difficulty with driving. Individuals with migraine may experience dizziness and/or vertigo, and these symptoms are most prominent in those with vestibular migraine.48 While vestibular dysfunction is not equivalent to vestibular symptoms occurring during migraine, the association of vestibular dysfunction with driving difficulty raises concern that individuals with migraine attacks accompanied by vestibular symptoms may experience similar difficulty.

Visual disturbances are common in migraine, both preceding an attack (visual aura) and during an attack (photophobia), and there is the potential for interference with the ability to operate a motor vehicle safely. Photophobia may be particularly problematic while driving at night, when facing bright headlights from oncoming vehicles. The overall burden associated with visual disturbances in migraine is not well understood. In a small study, investigators reported that vision‐specific quality of life scores was lower in individuals with migraine vs healthy controls, particularly for those with chronic migraine (vs episodic).49 More data are needed to elucidate whether there is any relationship between deficits in visual quality of life and driving impairment.

In conclusion, while it seems likely that symptoms occurring as part of the migraine attack (for example, pain, cognitive impairment, sleepiness, dizziness, and vertigo, and visual disturbances) could impact driving performance, formal study in this area is lacking. Generally, and understandably, studies of the effect of pain on driving ability have focused on the effect of treatment (opioids, for example) rather than the pain symptom itself. The impact of treatment on driving ability is further explored in the following paragraphs.

Impact of Treatment on Driving Performance

The potential for some classes of medications to influence driving ability is well recognized.50, 51, 52 Even over‐the‐counter medications for minor ailments, such as antihistamines for seasonal allergies, can result in drowsiness and impair driving ability; patients are not always aware of these side effects.53, 54

Treatments for migraine include acute treatments taken at the time of an attack to reduce pain and associated symptoms,55 and preventive medications to decrease attack frequency.56 Currently available medications for acute treatment include triptans, nonsteroidal anti‐inflammatory drugs (NSAIDs), acetaminophen, opioids, butalbital (a barbiturate, compounded with one or more other agents eg, aspirin, acetaminophen, caffeine, codeine phosphate), and ergot (taken as monotherapy or in combination), with the most recommended treatments being analgesics and triptans.55, 57 Where necessary, antiemetics may also be employed.55 Commonly prescribed preventive treatments include β‐blockers, antidepressants, topiramate, divalproex, calcitonin gene‐related peptide monoclonal antibodies, and onabotulinumtoxinA. The side effects of acute and preventive migraine treatments that are of relevance to driving are summarized in Table 1. Drowsiness and sleepiness are known side effects with triptans, opioids, butalbital and antiemetics, and can also occur with NSAIDs. Dizziness is a recognized side effect with triptans, opioids, and butalbital.

Table 1

Side Effects of Common Migraine Treatments With Potential to Effect Driving Performance

Treatment	Possible Effects Relevant to Driving Key scientific literature United States Prescribing Information (USPI)
Acute treatments
Triptans	CNS side effects (eg, dizziness, somnolence, fatigue) associated with triptan use. Incidence increases with increasing dose and is dependent upon which triptan is used (lower with sumatriptan, higher with eletriptan)58
Almotriptan	PI: May cause dizziness, sleepiness, and problems seeing. Do not drive, operate machinery, or do other dangerous activities until you know how drug affects you 59
Frovatriptan	PI: Can cause dizziness, weakness, or drowsiness. If you have these symptoms do not drive a car, use machinery, or do anything where you need to be alert 60
Sumatriptan	PI: Can cause dizziness, weakness, or drowsiness. If you have these symptoms, do not drive a car, use machinery, or do anything where you need to be alert 61
Rizatriptan	PI: May cause dizziness, weakness, or fainting. If you have these symptoms, do not drive a car, use machinery, or do anything that needs you to be alert 62
Eletriptan	PI: Can cause dizziness, weakness, or drowsiness. If you have these symptoms, do not drive a car, use machinery, or do anything where you need to be alert 63
Naratriptan	PI: Can cause dizziness, weakness, or drowsiness. If you have these symptoms, do not drive a car, use machinery, or do anything where you need to be alert 64
Zolmitriptan	PI: No relevant information included65
Opioids	Use associated with increased risk of road trauma50, 66 PI for hydrocodone bitartrate and acetaminophen tablets: May impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery; patients should be cautioned accordingly 67
Butalbital (barbiturate)	Associated with increased risk of road trauma68 PI: … may impair mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Such tasks should be avoided while taking this product 69
Preventive treatments
Propranolol (β‐blocker)	PI: Light‐headedness, mental depression manifested by insomnia, lassitude, weakness, fatigue; catatonia; visual disturbances; hallucinations; vivid dreams; an acute reversible syndrome characterized by disorientation for time and place, short‐term memory loss, emotional lability, slightly clouded sensorium, and decreased performance on neuropsychometrics 70
Amitriptyline (TCA)	TCAs associated with cognitive impairment71 PI: While on therapy with amitriptyline hydrochloride, patients should be advised to the possible impairment of mental and/or physical abilities required for the performance of hazardous tasks, such as operating machinery or driving a motor vehicle 72
Anti‐epileptic treatments	Have been associated with increased incidence of MVCs50
Topiramate	PI: Cognitive/neuropsychiatric adverse reactions: use caution when operating machinery including cars; depression and mood problems may occur 73
Divalproex (valproic acid derivative)	PI: Can cause drowsiness and dizziness. Do not drive a car or operate dangerous machinery until you know how drug affects you 74
Gabapentin	PI: Driving Impairment; Somnolence/Sedation and Dizziness: Warn patients not to drive until they have gained sufficient experience to assess whether their ability to drive or operate heavy machinery will be impaired 75
OnabotulinumtoxinA	PI: Patients should be counseled that if loss of strength, muscle weakness, blurred vision, or drooping eyelids occur, they should avoid driving a car or engaging in other potentially hazardous activities 76
CGRP antagonists	PI: No relevant information included for erenumab,77 fremanezumab,78 or galcanezumab79

CGRP = calcitonin gene‐related peptide; CNS = central nervous system; TCA = tricyclic antidepressant.

While side effects associated with treatment can be similar to symptoms experienced in a migraine attack (for example, dizziness or drowsiness), treatment also alleviates the symptoms of an attack. If acute treatment leads to prompt resolution of migraine, driving might actually improve as a result of a reduction in all of the migraine‐associated symptoms. For example, in small studies, sumatriptan nasal spray has been shown to reverse migraine‐related cognitive deficits observed during an untreated attack.35, 80 Of course, the benefits of treatment on symptoms that impair driving could be outweighed by treatment side effects.

The side effects of treatments may vary from population to population, and studies in healthy controls may not be directly applicable to individuals with migraine. The incidence of adverse events associated with topiramate use appears to be disorder dependent. An analysis comparing data from double‐blind, randomized controlled trials of topiramate in migraine and in newly diagnosed epilepsy found that the incidence of paresthesia, cognitive symptoms, as well as discontinuations, associated with topiramate was higher in individuals with migraine vs those with epilepsy.81

Lasmiditan, a selective serotonin (5‐HT) 1F agonist (a ditan), was approved by the FDA in October 2019 for the acute treatment of migraine in adults. The effect of lasmiditan on simulated driving performance was examined in healthy adults, consistent with guidance recently issued by the FDA.22 In simulated driving studies, lasmiditan was associated with clinically meaningful impairment of simulated driving performance at 1.5 hours postdose, around the time when lasmiditan is at peak concentration in the blood, and that impairment resolved by 8 hours.82 Findings from these studies to assess directly the effect of a migraine treatment on driving (under simulated conditions) are the first to be published in this area.

As a result of the development of new migraine treatments and the recent FDA guidance document outlining the circumstances under which drug developers need to assess the effects of a new treatment on driving ability,22 there will be increasing focus on migraine and driving. In other disease states, treatments are already being tested in driving studies.83, 84, 85 Conducting specific driving studies will result in the inclusion of more specific wording related to driving in the prescribing information. The FDA guidance document22 instructs that studies of driving impairment should be described in the Clinical Studies section of labeling, including a brief description of the design and pertinent results, and that safety information from driving studies should be included in other sections of labeling as appropriate, including Warning and Precautions, Patient Counseling Information, and FDA‐approved patient labeling. Recently, two placebo‐controlled studies were conducted to assess the effects of SpravatoTM (esketamine), indicated for treatment of treatment‐resistant depression, on the ability to drive; the findings resulted in the inclusion of the following warning in the PI – “Impaired Ability to Drive and Operate Machinery: Do not drive or operate machinery until the next day after a restful sleep.”86

In conclusion, some of the approved treatments for migraine have the potential to impact driving, yet this topic has not generally been specifically studied, and the extent to which these risks are communicated to patients is not clear. Increased focus on the effects of medications on driving, including regulatory guidance on this topic, will ensure that more information on any potential impact on driving will be available for newly approved drugs. While many of these treatments include precautionary statements in their labeling, patient education on the effects of medication on driving will also require increased attention.

Future Directions

Based on this assessment of the current literature, there is insufficient data to support or refute driving impairment or an increased risk of MVCs in individuals with migraine. To generate more robust data on this topic, definitive studies designed to distinguish the effect of disease from that of treatment are required. The authors acknowledge the difficulties that may accompany these evaluations.

A full review of the methodology to assess driving performance is beyond the scope of this manuscript. However, it is worth noting the current regulatory recommendations in the United States. In their recent guidance on evaluating drug effects on the ability to operate a motor vehicle,22 the FDA recommends a tiered approach. Using this approach, relevant information obtained early in the drug development (pharmacological, toxicological, epidemiological, phase 1 clinical information) is used to guide continued clinical study and to characterize the clinical relevance of findings. When an early study suggests the potential for CNS impairment, this should be investigated further. The FDA recommended that the broad functional domains of alertness/arousal/wakefulness, attention and processing speed, reaction time/psychomotor functions, sensory‐perceptual functioning, and executive functions (all relevant to driving) should be assessed with increasingly focused studies. If accumulating data suggests a potential for driving impairment, then dedicated driving studies may be required to assess more specifically the effect of the drug on driving performance. On‐the‐road driving assessment and driving simulators are recommended. The FDA guidance document notes that the need to evaluate driving performance depends upon a number of factors, including the indications for use of the drug, the intended patient population, and the severity of the CNS impairing effects.

Cognitive tests that permit an accurate and reliable assessment of a complex real world activity provide valuable contributions to societal health. The King‐Devick test, for example, provides a rapid sideline screening for concussion, useful in improving sports safety.87 The driving simulator and on‐the‐road driving test are currently considered state of the art for measurements of driving performance, although this methodology is not readily available to all. A neurocognitive assessment that replicates results of driving simulators or on‐the‐road tests would facilitate broader assessment of driving ability in clinical practice. To date, this research has not been fruitful, with modest associations between individual cognitive tests and driving performance and inconsistent findings across studies. Further research to identify predictors of impaired driving, and to reliably detect and assess this complex behavior, would be beneficial. Importantly, measurements should be objective rather than subjective, since drivers poorly predict their own driving impairment.88

Discussion

Migraine has a substantial impact on patient function and quality of life27, 89, 90 and is the second largest disease cause of years lost to disability.91 The impact of migraine on an individual's driving performance has been largely neglected, and studies to date have not distinguished ictal and interictal effects or the confounding effects of medication and comorbidities.

A reliable test, or battery of tests, are needed to evaluate effects of both disease and treatment, with the recognition that treatment can both relieve and contribute to symptoms that may impair driving. Ultimately, studies need to address real world scenarios. For example, migraine attacks commonly occur away from home and, if driving impairment is a concern, may force the decision as to whether to travel home without treatment before symptoms become incapacitating, treat in anticipation, or make alternative plans to avoid driving.

As the effects of certain medical conditions and drug treatments on driving receive more attention, the implications of increased knowledge will need to be considered. Specifically, if well designed studies support an association between migraine and impaired driving, how will this influence the diagnosis and management of the patient with migraine? Potential outcomes include a greater opportunity for patient and healthcare provider recognition and education of the potential impact of migraine on driving.

Conclusion

The impact of migraine on an individual's driving performance has been largely neglected, with few studies specifically designed to address this topic. With a potential for impact on road safety, this area requires more focus.