Sleep Medicine

Concussion, also known as mild traumatic brain injury, affects more than 600 adults per 100,000 each year and is commonly treated by nonneurologists.¹ Public attention to concussion has been increasing, particularly to concussion sustained during sports. Coincident with this increased attention, the diagnosis of concussion continues to increase in the outpatient setting. Thus, a review of the topic is timely.

ACCELERATION OF THE BRAIN DUE TO TRAUMA

The definition of concussion has changed considerably over the years. It is currently defined as a pathophysiologic process that results from an acceleration or deceleration of the brain induced by trauma.² It is largely a temporary, functional problem, as opposed to a gross structural injury.^2–5

The acceleration of the brain that results in a concussion is usually initiated by a direct blow to the head, although direct impact is not required.⁶ As the brain rotates, different areas accelerate at different rates, resulting in a shear strain imparted to the parenchyma.

This shear strain causes deformation of axonal membranes and opening of membrane-associated sodium-potassium channels. This in turn leads to release of excitatory neurotransmitters, ultimately culminating in a wave of neuronal depolarization and a spreading depression-like phenomenon that may mediate the loss of consciousness, posttraumatic amnesia, confusion, and many of the other immediate signs and symptoms associated with concussion.

The sudden metabolic demand created by the massive excitatory phenomena triggers an increased utilization of glucose to restore cellular homeostasis. At the same time, cerebral blood flow decreases after concussion, which, in the setting of increased glucose demand, leads to an “energy crisis”: an increased need for adenosine triphosphate with a concomitant decreased delivery of glucose.⁷ This mismatch between energy demand and supply is thought to underlie the most common signs and symptoms of concussion.

ASSESSMENT

History

The history of present illness is essential to a diagnosis of concussion. In the classic scenario, an otherwise asymptomatic person sustains some trauma to the head that is followed immediately by the signs and symptoms of concussion.

Many of these signs and symptoms are nonspecific and may occur without concussion or other trauma.^8,9 Thus, the diagnosis of concussion cannot be made on the basis of symptoms alone, but only in the overall context of history, physical examination, and, at times, additional clinical assessments.

The symptoms of concussion should gradually improve. While they may be exacerbated by certain activities or stimuli, the overall trend should be one of symptom improvement. If symptoms are worsening over time, alternative explanations for the patient’s symptoms should be considered.

Physical examination

A thorough neurologic examination should be conducted in all patients with suspected concussion and include the following.

A mental status examination should include assessment of attention, memory, and recall. Orientation is normal except in the most acute examinations.

Cranial nerve examination must include careful assessment of eye-movement control, including smooth pursuit and saccades. However, even in patients with prominent subjective dizziness, considerable experience may be needed to actually demonstrate abnormalities.

Balance testing. Balance demands careful assessment and, especially for young athletes, this testing should be more difficult than the tandem gait and eyes-closed, feet-together tests.

Standard strength, sensory, reflex, and coordination testing is usually normal.

Any focal neurologic findings should prompt consideration of other causes or of a more serious injury and should lead to further evaluation, including brain imaging.

Diagnostic tests

Current clinical brain imaging cannot diagnose a concussion. The purpose of neuroimaging is to assess for other etiologies or injuries, such as hemorrhage or contusion, that may cause similar symptoms but require different management.

Several guidelines are available to assess the need for imaging in the setting of recent trauma, of which 2 are typically used^10–12:

The Canadian CT Head Rule¹⁰ states that computed tomography (CT) is indicated in any of the following situations:

• The patient fails to reach a Glasgow Coma Scale score of 15—on a scale of 3 (worst) to 15 (best)—within 2 hours
• There is a suspected open skull fracture
• There is any sign of basal skull fracture
• The patient has 2 or more episodes of vomiting
• The patient is 65 or older
• The patient has retrograde amnesia (ie, cannot remember events that occurred before the injury) for 30 minutes or more
• The mechanism of injury was dangerous (eg, a pedestrian was struck by a motor vehicle, or the patient fell from > 3 feet or > 5 stairs).

The New Orleans Criteria¹¹ state that a patient warrants CT of the head if any of the following is present:

• Severe headache
• Vomiting
• Age over 60
• Drug or alcohol intoxication
• Deficit in short-term memory
• Physical evidence of trauma above the clavicles
• Seizure.

Caveats: these imaging guidelines apply to adults; those for pediatric patients differ.¹² Also, because they were designed for use in an emergency department, their utility in clinical practice outside the emergency department is unclear.

Electroencephalography is not necessary in the evaluation of concussion unless a seizure disorder is believed to be the cause of the injury.

Concussion in athletes

Athletes who participate in contact and collision sports are at higher risk of concussion than the nonathletic population. Therefore, specific assessments of symptoms, balance, oculomotor function, cognitive function, and reaction time have been developed for athletes.

Ideally, these measures are taken at preseason baseline, so that they are available for comparison with postinjury assessments after a known or suspected concussion. These assessments can be used to help make the diagnosis of concussion in cases that are unclear and to help monitor recovery. Objective measures of injury are especially useful for athletes who may be reluctant to report symptoms in order to return to play.

Like most medical tests, these assessments need to be properly interpreted in the overall context of the medical history and physical examination by those who know how to administer them. It is important to remember that the natural history of concussion recovery differs between sport-related concussion and concussion that occurs outside of sports.⁸

The symptoms and signs after concussion are so variable and multidimensional that they make a generally applicable treatment hard to define.

Rest: Physical and cognitive

Treatment depends on the specifics of the injury, but there are common recommendations for the acute days after injury. Lacking hard data, the consensus among experts is that patients should undergo a period of physical and cognitive rest.^13,14 Exactly what “rest” means and how long it should last are unknown, leading to a wide variation in its application.

Rest aids recovery but also may have adverse effects: fatigue, diurnal sleep disruption, reactive depression, anxiety, and physiologic deconditioning.^15,16 Many guidelines recommend physical and cognitive rest until symptoms resolve,¹⁴ but this is likely too cautious. Even without a concussion, inactivity is associated with many of the nonspecific symptoms also associated with concussion. As recovery progresses, the somatic symptoms of concussion improve, while emotional symptoms worsen, likely in part due to prolonged rest.¹⁷

We recommend a period of rest lasting 3 to 5 days after injury, followed by a gradual resumption of both physical and cognitive activities as tolerated, remaining below the level at which symptoms are exacerbated.

Not surprisingly, many guidelines for returning to physical activity are focused on athletes. Yet the same principles apply to management of concussion in the general population who exercise: light physical activity (typically walking or stationary bicycling), followed by more vigorous aerobic activity, followed by some resistance activities. Mild aerobic exercise (to below the threshold of symptoms) may speed recovery from refractive postconcussion syndrome, even in those who did not exercise before the injury.¹⁸

Athletes require specific and strict instructions to avoid increased trauma to the head during the gradual increase of physical activities. The National Collegiate Athletic Association has published an algorithm for a gradual return to sport-specific training that is echoed in recent consensus statements on concussion.¹⁹ Once aerobic reconditioning produces no symptoms, then noncontact, sport-specific activities are begun, followed by contact activities. We have patients return to the clinic once they are symptom-free for repeat evaluation before clearing them for high-risk activities (eg, skiing, bicycling) or contact sports (eg, basketball, soccer, football, ice hockey).

Cognitive rest

While physical rest is fairly straightforward, cognitive rest is more challenging. The concept of cognitive rest is hard to define and even harder to enforce. Patients are often told to minimize any activities that require attention or concentration. This often includes, but is not limited to, avoiding reading, texting, playing video games, and using computers.¹³

In the modern world, full avoidance of these activities is difficult and can be profoundly socially isolating. Further, complete cognitive rest may be associated with symptoms of its own.^15,16,20 Still, some reasonable limitation of cognitive activities, at least initially, is likely beneficial.²¹ For patients engaged in school or academic work, often the daily schedule needs to be adjusted and accommodations made to help them return to a full academic schedule and level of activity. It is reasonable to have patients return gradually to work or school rather than attempt to immediately return to their preinjury level.

With these interventions, most patients have full resolution of their symptoms and return to preinjury levels of performance.

TREATING SOMATIC SYMPTOMS

Posttraumatic headache

Posttraumatic headache is the most common sequela of concussion.²² Surprisingly, it is more common after concussion than after moderate or severe traumatic brain injury.²³ A prior history of headache, particularly migraine, is a known risk factor for development of posttraumatic headache.²⁴

Posttraumatic headache is usually further defined by headache type using the International Classification of Headache Disorders criteria (www.ichd-3.org). Migraine or probable migraine is the most common type of posttraumatic headache; tension headache is less common.²⁵

Analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) are often used initially by patients to treat posttraumatic headache. One study found that 70% of patients used acetaminophen or an NSAID.²⁶

Treating early with effective therapy is the most important tenet of posttraumatic headache treatment, since 80% of those who self-treat have incomplete relief, and almost all of them are using over-the-counter products.²⁷ Overuse of over-the-counter abortive medications can lead to medication overuse headache, also known as rebound headache, thus complicating the treatment of posttraumatic headache.²⁶

Earlier treatment with a preventive medication can often limit the need for and overuse of over-the-counter analgesics and can minimize the occurrence of subsequent medication overuse headache. However, in pediatric populations, nonpharmacologic interventions such as rest and sleep hygiene are typically used first, then medications after 4 to 6 weeks if this is ineffective.

A number of medications have been studied for prophylactic treatment of posttraumatic headache, including topiramate, amitriptyline, and divalproex sodium,^28–30 but there is little compelling evidence for use of one over the other. If posttraumatic headache is migrainous, beta-blockers, calcium-channel blockers, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibtors, and gabapentin are other prophylactic medication options under the appropriate circumstances.^27,31,32 In adults, we have clinically had success with nortriptyline 20 mg or gabapentin 300 mg at night as an initial prophylactic headache medication, increasing as tolerated or until pain is controlled, though there are no high-quality data to guide this decision.

The ideal prophylactic medication depends on headache type, patient tolerance, comorbidities, allergies, and medication sensitivities. Gabapentin, amitriptyline, and nortriptyline can produce sedation, which can help those suffering from sleep disturbance.

If a provider is not comfortable prescribing these medications or doesn’t prescribe them regularly, the patient should be referred to a concussion or headache specialist more familiar with their use.

In some patients, even some athletes, headache may be related to a cervical strain injury—whiplash—that should be treated with an NSAID (or acetaminophen), perhaps with a short course of a muscle relaxant in adults, and with physical therapy.³²

Some patients have chronic headache despite oral medications.²⁶ Therefore, alternatives to oral medications and complementary therapies should be considered. Especially for protracted cases requiring more complicated headache management or injectable treatments, patients should be referred to a pain clinic, headache specialist, or concussion specialist.

Dizziness is also common after concussion. But what the patient means by dizziness requires a little probing. Some have paroxysms of vertigo. This typically represents a peripheral vestibular injury, usually benign paroxysmal positional vertigo. The latter can be elicited with a Hallpike maneuver and treated in the office with the Epley maneuver.³³

Usually, dizziness is a subjective sense of poor coordination, gait instability, or dysequilibrium. Patients may also complain of associated nausea and motion sensitivity. This may all be secondary to a mechanism in the middle or inner ear or the brain. Patients should be encouraged to begin movement—gradually and safely—to help the vestibular system accommodate, which it will do with gradual stimulation. It usually resolves spontaneously.

Specific treatment is unfortunately limited. There is no established benefit from vestibular suppressants such as meclizine. Vestibular rehabilitation may accelerate improvement and decrease symptoms.³³ Referral for a comprehensive balance assessment or to vestibular therapy (a subset of physical therapy) should be considered and is something we typically undertake in our clinic if there is no recovery from dizziness 4 to 6 weeks after the concussion.

Visual symptoms can contribute to dizziness. Convergence spasm or convergence insufficiency (both related to muscle spasm of the eye) can occur after concussion, with some studies estimating that up to 69% of patients have these symptoms.³⁴ This can interfere with visual tracking and contribute to a feeling of dysequilibrium.³⁴ Referral to a concussion specialist or vestibular rehabilitation physical therapist can be helpful in treating this issue if it does not resolve spontaneously.

Orthostasis and lightheadedness also contribute to dizziness and are associated with cerebrovascular autoregulation. Available data suggest that dysregulation of neurovascular coupling, cerebral vasoreactivity, and cerebral autoregulation contribute to some of the chronic symptoms of concussion, including dizziness. A gradual return to exercise may help regulate cerebral blood flow and improve this type of dizziness.³⁵

Sleep disturbance

Sleep disturbance is common after concussion, but the form is variable: insomnia, excessive daytime somnolence, and alteration of the sleep-wake cycle are all seen and may themselves affect recovery.³⁶

Sleep hygiene education should be the first intervention for postconcussive sleep issues. For example, the patient should be encouraged to do the following:

• Minimize “screen time” an hour before going to bed: cell phone, tablet, and computer screens emit a wavelength of light that suppresses endogenous melatonin release^37,38
• Go to bed and wake up at the same time each day
• Minimize or avoid caffeine, nicotine, and alcohol
• Avoid naps.³⁹

Melatonin is a safe and effective treatment that could be added.⁴⁰ In addition, some studies suggest that melatonin may improve recovery from traumatic brain injury.^41,42

Mild exercise (to below the threshold of causing or exacerbating symptoms) may also improve sleep quality.

Amitriptyline or nortriptyline may reduce headache frequency and intensity and also help treat insomnia.

Trazodone is recommended by some as a first-line agent,³⁹ but we usually reserve it for protracted insomnia refractory to the above treatments.

Benzodiazepines should be avoided, as they reduce arousal, impair cognition, and exacerbate motor impairments.⁴³

Emotional symptoms

Acute-onset anxiety or depression often occurs after concussion.^44,45 There is abundant evidence that emotional effects of injury may be the most significant factor in recovery.⁴⁶ A preinjury history of anxiety may be a prognostic factor.⁹ Patients with a history of anxiety or depression are more likely to develop emotional symptoms after a concussion, but emotional problems may develop in any patient after a concussion.^47,48

The circumstances under which an injury is sustained may be traumatic (eg, car accident, assault), leading to an acute stress reaction or disorder and, if untreated, may result in a more chronic condition—posttraumatic stress disorder. Moreover, the injury and subsequent symptoms may have repercussions in many aspects of the patient’s life, leading to further psychologic stress (eg, loss of wages or the inability to handle normal work, school, and family responsibilities).

Referral to a therapist trained in skills-based psychotherapy (eg, cognitive-behavioral therapy, exposure-based treatment) is often helpful.

Pharmacologic treatment can be a useful adjunct. Several studies have shown that selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants may improve depression after concussion.⁴⁹ The prescription of antidepressants, however, is best left to providers with experience in treating anxiety and depression.

As with sleep disorders after concussion, benzodiazepines should be avoided, as they can impair cognition.⁴³

Cognitive problems

Cognitive problems are also common after concussion. Patients complain about everyday experiences of forgetfulness, distractibility, loss of concentration, and mental fatigue. Although patients often subjectively perceive these symptoms as quite limiting, the impairments can be difficult to demonstrate in office testing.

A program of gradual increase in mental activity, parallel to recovery of physical capacity, should be undertaken. Most patients make a gradual recovery within a few weeks.⁵⁰

When cognitive symptoms cause significant school or vocational problems or become persistent, patients should be referred to a specialty clinic. As with most of the consequences of concussion, there are few established treatments. When cognitive difficulties persist, it is important to consider the complications of concussion mentioned above: headache, pain, sleep disturbance, and anxiety, all of which may cause subjective cognitive problems and are treatable.

If cognitive symptoms are prolonged despite improvement of other issues like headache and sleep disturbance, a low-dose stimulant medication such as amphetamine salts or methylphenidate may be useful for symptoms of poor attention.⁴⁹ They should be only a temporary measure after concussion to carry the patient through a cognitively challenging period, unless there was a history of attention-deficit disorder before the injury. A variety of other agents, including amantadine,⁵¹ have been proposed based on limited studies; all are off-label uses. Before considering these types of interventions, referral to a specialist or a specialty program would be appropriate.

With the interventions suggested above, most patients with concussion have a resolution of symptoms and can return to preinjury levels of performance. But some have prolonged symptoms and sequelae. Approximately 10% of athletes have persistent signs and symptoms of concussion beyond 2 weeks. If concussion is not sport-related, most patients recover completely within the first 3 months, but up to 33% may have symptoms beyond that.⁵²

Four types of patients have persistent symptoms:

Patients who sustained a high-force mechanism of injury. These patients simply need more time and accommodation.

Patients who sustained multiple concussions. These patients may also need more time and accommodation.

Patients with an underlying neurologic condition, recognized prior to injury or not, may have delayed or incomplete recovery. Even aging may be an “underlying condition” in concussion.

Patients whose symptoms from an apparently single mild concussion do not resolve despite appropriate treatments may have identifiable factors, but intractable pain (usually headache) or significant emotional disturbance or both are common. Once established and persistent, this is difficult to treat. Referral to a specialty practice is appropriate, but even in that setting effective treatment may be elusive.

PATIENT EDUCATION

Most important for patient education is reassurance. Ultimately, concussion is a self-limited phenomenon, and reinforcing this is helpful for patients. If concussion is not sport-related, most patients recover completely within 3 months.

The next important tenet in patient education is that they should rest for 3 to 5 days, then resume gradual physical and cognitive activities. If resuming activities too soon results in symptoms, then they should rest for a day and gradually resume activity. If their recovery is prolonged (ie, longer than 6 weeks), they likely need to be referred to a concussion specialist.

Concussion, also known as mild traumatic brain injury, affects more than 600 adults per 100,000 each year and is commonly treated by nonneurologists.¹ Public attention to concussion has been increasing, particularly to concussion sustained during sports. Coincident with this increased attention, the diagnosis of concussion continues to increase in the outpatient setting. Thus, a review of the topic is timely.

ACCELERATION OF THE BRAIN DUE TO TRAUMA

The definition of concussion has changed considerably over the years. It is currently defined as a pathophysiologic process that results from an acceleration or deceleration of the brain induced by trauma.² It is largely a temporary, functional problem, as opposed to a gross structural injury.^2–5

The acceleration of the brain that results in a concussion is usually initiated by a direct blow to the head, although direct impact is not required.⁶ As the brain rotates, different areas accelerate at different rates, resulting in a shear strain imparted to the parenchyma.

This shear strain causes deformation of axonal membranes and opening of membrane-associated sodium-potassium channels. This in turn leads to release of excitatory neurotransmitters, ultimately culminating in a wave of neuronal depolarization and a spreading depression-like phenomenon that may mediate the loss of consciousness, posttraumatic amnesia, confusion, and many of the other immediate signs and symptoms associated with concussion.

The sudden metabolic demand created by the massive excitatory phenomena triggers an increased utilization of glucose to restore cellular homeostasis. At the same time, cerebral blood flow decreases after concussion, which, in the setting of increased glucose demand, leads to an “energy crisis”: an increased need for adenosine triphosphate with a concomitant decreased delivery of glucose.⁷ This mismatch between energy demand and supply is thought to underlie the most common signs and symptoms of concussion.

ASSESSMENT

History

The history of present illness is essential to a diagnosis of concussion. In the classic scenario, an otherwise asymptomatic person sustains some trauma to the head that is followed immediately by the signs and symptoms of concussion.

Many of these signs and symptoms are nonspecific and may occur without concussion or other trauma.^8,9 Thus, the diagnosis of concussion cannot be made on the basis of symptoms alone, but only in the overall context of history, physical examination, and, at times, additional clinical assessments.

The symptoms of concussion should gradually improve. While they may be exacerbated by certain activities or stimuli, the overall trend should be one of symptom improvement. If symptoms are worsening over time, alternative explanations for the patient’s symptoms should be considered.

Physical examination

A thorough neurologic examination should be conducted in all patients with suspected concussion and include the following.

A mental status examination should include assessment of attention, memory, and recall. Orientation is normal except in the most acute examinations.

Cranial nerve examination must include careful assessment of eye-movement control, including smooth pursuit and saccades. However, even in patients with prominent subjective dizziness, considerable experience may be needed to actually demonstrate abnormalities.

Balance testing. Balance demands careful assessment and, especially for young athletes, this testing should be more difficult than the tandem gait and eyes-closed, feet-together tests.

Standard strength, sensory, reflex, and coordination testing is usually normal.

Any focal neurologic findings should prompt consideration of other causes or of a more serious injury and should lead to further evaluation, including brain imaging.

Diagnostic tests

Current clinical brain imaging cannot diagnose a concussion. The purpose of neuroimaging is to assess for other etiologies or injuries, such as hemorrhage or contusion, that may cause similar symptoms but require different management.

Several guidelines are available to assess the need for imaging in the setting of recent trauma, of which 2 are typically used^10–12:

The Canadian CT Head Rule¹⁰ states that computed tomography (CT) is indicated in any of the following situations:

• The patient fails to reach a Glasgow Coma Scale score of 15—on a scale of 3 (worst) to 15 (best)—within 2 hours
• There is a suspected open skull fracture
• There is any sign of basal skull fracture
• The patient has 2 or more episodes of vomiting
• The patient is 65 or older
• The patient has retrograde amnesia (ie, cannot remember events that occurred before the injury) for 30 minutes or more
• The mechanism of injury was dangerous (eg, a pedestrian was struck by a motor vehicle, or the patient fell from > 3 feet or > 5 stairs).

The New Orleans Criteria¹¹ state that a patient warrants CT of the head if any of the following is present:

• Severe headache
• Vomiting
• Age over 60
• Drug or alcohol intoxication
• Deficit in short-term memory
• Physical evidence of trauma above the clavicles
• Seizure.

Caveats: these imaging guidelines apply to adults; those for pediatric patients differ.¹² Also, because they were designed for use in an emergency department, their utility in clinical practice outside the emergency department is unclear.

Electroencephalography is not necessary in the evaluation of concussion unless a seizure disorder is believed to be the cause of the injury.

Concussion in athletes

Athletes who participate in contact and collision sports are at higher risk of concussion than the nonathletic population. Therefore, specific assessments of symptoms, balance, oculomotor function, cognitive function, and reaction time have been developed for athletes.

Ideally, these measures are taken at preseason baseline, so that they are available for comparison with postinjury assessments after a known or suspected concussion. These assessments can be used to help make the diagnosis of concussion in cases that are unclear and to help monitor recovery. Objective measures of injury are especially useful for athletes who may be reluctant to report symptoms in order to return to play.

Like most medical tests, these assessments need to be properly interpreted in the overall context of the medical history and physical examination by those who know how to administer them. It is important to remember that the natural history of concussion recovery differs between sport-related concussion and concussion that occurs outside of sports.⁸

The symptoms and signs after concussion are so variable and multidimensional that they make a generally applicable treatment hard to define.

Rest: Physical and cognitive

Treatment depends on the specifics of the injury, but there are common recommendations for the acute days after injury. Lacking hard data, the consensus among experts is that patients should undergo a period of physical and cognitive rest.^13,14 Exactly what “rest” means and how long it should last are unknown, leading to a wide variation in its application.

Rest aids recovery but also may have adverse effects: fatigue, diurnal sleep disruption, reactive depression, anxiety, and physiologic deconditioning.^15,16 Many guidelines recommend physical and cognitive rest until symptoms resolve,¹⁴ but this is likely too cautious. Even without a concussion, inactivity is associated with many of the nonspecific symptoms also associated with concussion. As recovery progresses, the somatic symptoms of concussion improve, while emotional symptoms worsen, likely in part due to prolonged rest.¹⁷

We recommend a period of rest lasting 3 to 5 days after injury, followed by a gradual resumption of both physical and cognitive activities as tolerated, remaining below the level at which symptoms are exacerbated.

Not surprisingly, many guidelines for returning to physical activity are focused on athletes. Yet the same principles apply to management of concussion in the general population who exercise: light physical activity (typically walking or stationary bicycling), followed by more vigorous aerobic activity, followed by some resistance activities. Mild aerobic exercise (to below the threshold of symptoms) may speed recovery from refractive postconcussion syndrome, even in those who did not exercise before the injury.¹⁸

Athletes require specific and strict instructions to avoid increased trauma to the head during the gradual increase of physical activities. The National Collegiate Athletic Association has published an algorithm for a gradual return to sport-specific training that is echoed in recent consensus statements on concussion.¹⁹ Once aerobic reconditioning produces no symptoms, then noncontact, sport-specific activities are begun, followed by contact activities. We have patients return to the clinic once they are symptom-free for repeat evaluation before clearing them for high-risk activities (eg, skiing, bicycling) or contact sports (eg, basketball, soccer, football, ice hockey).

Cognitive rest

While physical rest is fairly straightforward, cognitive rest is more challenging. The concept of cognitive rest is hard to define and even harder to enforce. Patients are often told to minimize any activities that require attention or concentration. This often includes, but is not limited to, avoiding reading, texting, playing video games, and using computers.¹³

In the modern world, full avoidance of these activities is difficult and can be profoundly socially isolating. Further, complete cognitive rest may be associated with symptoms of its own.^15,16,20 Still, some reasonable limitation of cognitive activities, at least initially, is likely beneficial.²¹ For patients engaged in school or academic work, often the daily schedule needs to be adjusted and accommodations made to help them return to a full academic schedule and level of activity. It is reasonable to have patients return gradually to work or school rather than attempt to immediately return to their preinjury level.

With these interventions, most patients have full resolution of their symptoms and return to preinjury levels of performance.

TREATING SOMATIC SYMPTOMS

Posttraumatic headache

Posttraumatic headache is the most common sequela of concussion.²² Surprisingly, it is more common after concussion than after moderate or severe traumatic brain injury.²³ A prior history of headache, particularly migraine, is a known risk factor for development of posttraumatic headache.²⁴

Posttraumatic headache is usually further defined by headache type using the International Classification of Headache Disorders criteria (www.ichd-3.org). Migraine or probable migraine is the most common type of posttraumatic headache; tension headache is less common.²⁵

Analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) are often used initially by patients to treat posttraumatic headache. One study found that 70% of patients used acetaminophen or an NSAID.²⁶

Treating early with effective therapy is the most important tenet of posttraumatic headache treatment, since 80% of those who self-treat have incomplete relief, and almost all of them are using over-the-counter products.²⁷ Overuse of over-the-counter abortive medications can lead to medication overuse headache, also known as rebound headache, thus complicating the treatment of posttraumatic headache.²⁶

Earlier treatment with a preventive medication can often limit the need for and overuse of over-the-counter analgesics and can minimize the occurrence of subsequent medication overuse headache. However, in pediatric populations, nonpharmacologic interventions such as rest and sleep hygiene are typically used first, then medications after 4 to 6 weeks if this is ineffective.

A number of medications have been studied for prophylactic treatment of posttraumatic headache, including topiramate, amitriptyline, and divalproex sodium,^28–30 but there is little compelling evidence for use of one over the other. If posttraumatic headache is migrainous, beta-blockers, calcium-channel blockers, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibtors, and gabapentin are other prophylactic medication options under the appropriate circumstances.^27,31,32 In adults, we have clinically had success with nortriptyline 20 mg or gabapentin 300 mg at night as an initial prophylactic headache medication, increasing as tolerated or until pain is controlled, though there are no high-quality data to guide this decision.

The ideal prophylactic medication depends on headache type, patient tolerance, comorbidities, allergies, and medication sensitivities. Gabapentin, amitriptyline, and nortriptyline can produce sedation, which can help those suffering from sleep disturbance.

If a provider is not comfortable prescribing these medications or doesn’t prescribe them regularly, the patient should be referred to a concussion or headache specialist more familiar with their use.

In some patients, even some athletes, headache may be related to a cervical strain injury—whiplash—that should be treated with an NSAID (or acetaminophen), perhaps with a short course of a muscle relaxant in adults, and with physical therapy.³²

Some patients have chronic headache despite oral medications.²⁶ Therefore, alternatives to oral medications and complementary therapies should be considered. Especially for protracted cases requiring more complicated headache management or injectable treatments, patients should be referred to a pain clinic, headache specialist, or concussion specialist.

Dizziness is also common after concussion. But what the patient means by dizziness requires a little probing. Some have paroxysms of vertigo. This typically represents a peripheral vestibular injury, usually benign paroxysmal positional vertigo. The latter can be elicited with a Hallpike maneuver and treated in the office with the Epley maneuver.³³

Usually, dizziness is a subjective sense of poor coordination, gait instability, or dysequilibrium. Patients may also complain of associated nausea and motion sensitivity. This may all be secondary to a mechanism in the middle or inner ear or the brain. Patients should be encouraged to begin movement—gradually and safely—to help the vestibular system accommodate, which it will do with gradual stimulation. It usually resolves spontaneously.

Specific treatment is unfortunately limited. There is no established benefit from vestibular suppressants such as meclizine. Vestibular rehabilitation may accelerate improvement and decrease symptoms.³³ Referral for a comprehensive balance assessment or to vestibular therapy (a subset of physical therapy) should be considered and is something we typically undertake in our clinic if there is no recovery from dizziness 4 to 6 weeks after the concussion.

Visual symptoms can contribute to dizziness. Convergence spasm or convergence insufficiency (both related to muscle spasm of the eye) can occur after concussion, with some studies estimating that up to 69% of patients have these symptoms.³⁴ This can interfere with visual tracking and contribute to a feeling of dysequilibrium.³⁴ Referral to a concussion specialist or vestibular rehabilitation physical therapist can be helpful in treating this issue if it does not resolve spontaneously.

Orthostasis and lightheadedness also contribute to dizziness and are associated with cerebrovascular autoregulation. Available data suggest that dysregulation of neurovascular coupling, cerebral vasoreactivity, and cerebral autoregulation contribute to some of the chronic symptoms of concussion, including dizziness. A gradual return to exercise may help regulate cerebral blood flow and improve this type of dizziness.³⁵

Sleep disturbance

Sleep disturbance is common after concussion, but the form is variable: insomnia, excessive daytime somnolence, and alteration of the sleep-wake cycle are all seen and may themselves affect recovery.³⁶

Sleep hygiene education should be the first intervention for postconcussive sleep issues. For example, the patient should be encouraged to do the following:

• Minimize “screen time” an hour before going to bed: cell phone, tablet, and computer screens emit a wavelength of light that suppresses endogenous melatonin release^37,38
• Go to bed and wake up at the same time each day
• Minimize or avoid caffeine, nicotine, and alcohol
• Avoid naps.³⁹

Melatonin is a safe and effective treatment that could be added.⁴⁰ In addition, some studies suggest that melatonin may improve recovery from traumatic brain injury.^41,42

Mild exercise (to below the threshold of causing or exacerbating symptoms) may also improve sleep quality.

Amitriptyline or nortriptyline may reduce headache frequency and intensity and also help treat insomnia.

Trazodone is recommended by some as a first-line agent,³⁹ but we usually reserve it for protracted insomnia refractory to the above treatments.

Benzodiazepines should be avoided, as they reduce arousal, impair cognition, and exacerbate motor impairments.⁴³

Emotional symptoms

Acute-onset anxiety or depression often occurs after concussion.^44,45 There is abundant evidence that emotional effects of injury may be the most significant factor in recovery.⁴⁶ A preinjury history of anxiety may be a prognostic factor.⁹ Patients with a history of anxiety or depression are more likely to develop emotional symptoms after a concussion, but emotional problems may develop in any patient after a concussion.^47,48

The circumstances under which an injury is sustained may be traumatic (eg, car accident, assault), leading to an acute stress reaction or disorder and, if untreated, may result in a more chronic condition—posttraumatic stress disorder. Moreover, the injury and subsequent symptoms may have repercussions in many aspects of the patient’s life, leading to further psychologic stress (eg, loss of wages or the inability to handle normal work, school, and family responsibilities).

Referral to a therapist trained in skills-based psychotherapy (eg, cognitive-behavioral therapy, exposure-based treatment) is often helpful.

Pharmacologic treatment can be a useful adjunct. Several studies have shown that selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants may improve depression after concussion.⁴⁹ The prescription of antidepressants, however, is best left to providers with experience in treating anxiety and depression.

As with sleep disorders after concussion, benzodiazepines should be avoided, as they can impair cognition.⁴³

Cognitive problems

Cognitive problems are also common after concussion. Patients complain about everyday experiences of forgetfulness, distractibility, loss of concentration, and mental fatigue. Although patients often subjectively perceive these symptoms as quite limiting, the impairments can be difficult to demonstrate in office testing.

A program of gradual increase in mental activity, parallel to recovery of physical capacity, should be undertaken. Most patients make a gradual recovery within a few weeks.⁵⁰

When cognitive symptoms cause significant school or vocational problems or become persistent, patients should be referred to a specialty clinic. As with most of the consequences of concussion, there are few established treatments. When cognitive difficulties persist, it is important to consider the complications of concussion mentioned above: headache, pain, sleep disturbance, and anxiety, all of which may cause subjective cognitive problems and are treatable.

If cognitive symptoms are prolonged despite improvement of other issues like headache and sleep disturbance, a low-dose stimulant medication such as amphetamine salts or methylphenidate may be useful for symptoms of poor attention.⁴⁹ They should be only a temporary measure after concussion to carry the patient through a cognitively challenging period, unless there was a history of attention-deficit disorder before the injury. A variety of other agents, including amantadine,⁵¹ have been proposed based on limited studies; all are off-label uses. Before considering these types of interventions, referral to a specialist or a specialty program would be appropriate.

With the interventions suggested above, most patients with concussion have a resolution of symptoms and can return to preinjury levels of performance. But some have prolonged symptoms and sequelae. Approximately 10% of athletes have persistent signs and symptoms of concussion beyond 2 weeks. If concussion is not sport-related, most patients recover completely within the first 3 months, but up to 33% may have symptoms beyond that.⁵²

Four types of patients have persistent symptoms:

Patients who sustained a high-force mechanism of injury. These patients simply need more time and accommodation.

Patients who sustained multiple concussions. These patients may also need more time and accommodation.

Patients with an underlying neurologic condition, recognized prior to injury or not, may have delayed or incomplete recovery. Even aging may be an “underlying condition” in concussion.

Patients whose symptoms from an apparently single mild concussion do not resolve despite appropriate treatments may have identifiable factors, but intractable pain (usually headache) or significant emotional disturbance or both are common. Once established and persistent, this is difficult to treat. Referral to a specialty practice is appropriate, but even in that setting effective treatment may be elusive.

PATIENT EDUCATION

Most important for patient education is reassurance. Ultimately, concussion is a self-limited phenomenon, and reinforcing this is helpful for patients. If concussion is not sport-related, most patients recover completely within 3 months.

The next important tenet in patient education is that they should rest for 3 to 5 days, then resume gradual physical and cognitive activities. If resuming activities too soon results in symptoms, then they should rest for a day and gradually resume activity. If their recovery is prolonged (ie, longer than 6 weeks), they likely need to be referred to a concussion specialist.

Concussion, also known as mild traumatic brain injury, affects more than 600 adults per 100,000 each year and is commonly treated by nonneurologists.¹ Public attention to concussion has been increasing, particularly to concussion sustained during sports. Coincident with this increased attention, the diagnosis of concussion continues to increase in the outpatient setting. Thus, a review of the topic is timely.

ACCELERATION OF THE BRAIN DUE TO TRAUMA

The definition of concussion has changed considerably over the years. It is currently defined as a pathophysiologic process that results from an acceleration or deceleration of the brain induced by trauma.² It is largely a temporary, functional problem, as opposed to a gross structural injury.^2–5

The acceleration of the brain that results in a concussion is usually initiated by a direct blow to the head, although direct impact is not required.⁶ As the brain rotates, different areas accelerate at different rates, resulting in a shear strain imparted to the parenchyma.

This shear strain causes deformation of axonal membranes and opening of membrane-associated sodium-potassium channels. This in turn leads to release of excitatory neurotransmitters, ultimately culminating in a wave of neuronal depolarization and a spreading depression-like phenomenon that may mediate the loss of consciousness, posttraumatic amnesia, confusion, and many of the other immediate signs and symptoms associated with concussion.

The sudden metabolic demand created by the massive excitatory phenomena triggers an increased utilization of glucose to restore cellular homeostasis. At the same time, cerebral blood flow decreases after concussion, which, in the setting of increased glucose demand, leads to an “energy crisis”: an increased need for adenosine triphosphate with a concomitant decreased delivery of glucose.⁷ This mismatch between energy demand and supply is thought to underlie the most common signs and symptoms of concussion.

ASSESSMENT

History

The history of present illness is essential to a diagnosis of concussion. In the classic scenario, an otherwise asymptomatic person sustains some trauma to the head that is followed immediately by the signs and symptoms of concussion.

Many of these signs and symptoms are nonspecific and may occur without concussion or other trauma.^8,9 Thus, the diagnosis of concussion cannot be made on the basis of symptoms alone, but only in the overall context of history, physical examination, and, at times, additional clinical assessments.

The symptoms of concussion should gradually improve. While they may be exacerbated by certain activities or stimuli, the overall trend should be one of symptom improvement. If symptoms are worsening over time, alternative explanations for the patient’s symptoms should be considered.

Physical examination

A thorough neurologic examination should be conducted in all patients with suspected concussion and include the following.

A mental status examination should include assessment of attention, memory, and recall. Orientation is normal except in the most acute examinations.

Cranial nerve examination must include careful assessment of eye-movement control, including smooth pursuit and saccades. However, even in patients with prominent subjective dizziness, considerable experience may be needed to actually demonstrate abnormalities.

Balance testing. Balance demands careful assessment and, especially for young athletes, this testing should be more difficult than the tandem gait and eyes-closed, feet-together tests.

Standard strength, sensory, reflex, and coordination testing is usually normal.

Any focal neurologic findings should prompt consideration of other causes or of a more serious injury and should lead to further evaluation, including brain imaging.

Diagnostic tests

Current clinical brain imaging cannot diagnose a concussion. The purpose of neuroimaging is to assess for other etiologies or injuries, such as hemorrhage or contusion, that may cause similar symptoms but require different management.

Several guidelines are available to assess the need for imaging in the setting of recent trauma, of which 2 are typically used^10–12:

The Canadian CT Head Rule¹⁰ states that computed tomography (CT) is indicated in any of the following situations:

• The patient fails to reach a Glasgow Coma Scale score of 15—on a scale of 3 (worst) to 15 (best)—within 2 hours
• There is a suspected open skull fracture
• There is any sign of basal skull fracture
• The patient has 2 or more episodes of vomiting
• The patient is 65 or older
• The patient has retrograde amnesia (ie, cannot remember events that occurred before the injury) for 30 minutes or more
• The mechanism of injury was dangerous (eg, a pedestrian was struck by a motor vehicle, or the patient fell from > 3 feet or > 5 stairs).

The New Orleans Criteria¹¹ state that a patient warrants CT of the head if any of the following is present:

• Severe headache
• Vomiting
• Age over 60
• Drug or alcohol intoxication
• Deficit in short-term memory
• Physical evidence of trauma above the clavicles
• Seizure.

Caveats: these imaging guidelines apply to adults; those for pediatric patients differ.¹² Also, because they were designed for use in an emergency department, their utility in clinical practice outside the emergency department is unclear.

Electroencephalography is not necessary in the evaluation of concussion unless a seizure disorder is believed to be the cause of the injury.

Concussion in athletes

Athletes who participate in contact and collision sports are at higher risk of concussion than the nonathletic population. Therefore, specific assessments of symptoms, balance, oculomotor function, cognitive function, and reaction time have been developed for athletes.

Ideally, these measures are taken at preseason baseline, so that they are available for comparison with postinjury assessments after a known or suspected concussion. These assessments can be used to help make the diagnosis of concussion in cases that are unclear and to help monitor recovery. Objective measures of injury are especially useful for athletes who may be reluctant to report symptoms in order to return to play.

Like most medical tests, these assessments need to be properly interpreted in the overall context of the medical history and physical examination by those who know how to administer them. It is important to remember that the natural history of concussion recovery differs between sport-related concussion and concussion that occurs outside of sports.⁸

The symptoms and signs after concussion are so variable and multidimensional that they make a generally applicable treatment hard to define.

Rest: Physical and cognitive

Treatment depends on the specifics of the injury, but there are common recommendations for the acute days after injury. Lacking hard data, the consensus among experts is that patients should undergo a period of physical and cognitive rest.^13,14 Exactly what “rest” means and how long it should last are unknown, leading to a wide variation in its application.

Rest aids recovery but also may have adverse effects: fatigue, diurnal sleep disruption, reactive depression, anxiety, and physiologic deconditioning.^15,16 Many guidelines recommend physical and cognitive rest until symptoms resolve,¹⁴ but this is likely too cautious. Even without a concussion, inactivity is associated with many of the nonspecific symptoms also associated with concussion. As recovery progresses, the somatic symptoms of concussion improve, while emotional symptoms worsen, likely in part due to prolonged rest.¹⁷

We recommend a period of rest lasting 3 to 5 days after injury, followed by a gradual resumption of both physical and cognitive activities as tolerated, remaining below the level at which symptoms are exacerbated.

Not surprisingly, many guidelines for returning to physical activity are focused on athletes. Yet the same principles apply to management of concussion in the general population who exercise: light physical activity (typically walking or stationary bicycling), followed by more vigorous aerobic activity, followed by some resistance activities. Mild aerobic exercise (to below the threshold of symptoms) may speed recovery from refractive postconcussion syndrome, even in those who did not exercise before the injury.¹⁸

Athletes require specific and strict instructions to avoid increased trauma to the head during the gradual increase of physical activities. The National Collegiate Athletic Association has published an algorithm for a gradual return to sport-specific training that is echoed in recent consensus statements on concussion.¹⁹ Once aerobic reconditioning produces no symptoms, then noncontact, sport-specific activities are begun, followed by contact activities. We have patients return to the clinic once they are symptom-free for repeat evaluation before clearing them for high-risk activities (eg, skiing, bicycling) or contact sports (eg, basketball, soccer, football, ice hockey).

Cognitive rest

While physical rest is fairly straightforward, cognitive rest is more challenging. The concept of cognitive rest is hard to define and even harder to enforce. Patients are often told to minimize any activities that require attention or concentration. This often includes, but is not limited to, avoiding reading, texting, playing video games, and using computers.¹³

In the modern world, full avoidance of these activities is difficult and can be profoundly socially isolating. Further, complete cognitive rest may be associated with symptoms of its own.^15,16,20 Still, some reasonable limitation of cognitive activities, at least initially, is likely beneficial.²¹ For patients engaged in school or academic work, often the daily schedule needs to be adjusted and accommodations made to help them return to a full academic schedule and level of activity. It is reasonable to have patients return gradually to work or school rather than attempt to immediately return to their preinjury level.

With these interventions, most patients have full resolution of their symptoms and return to preinjury levels of performance.

TREATING SOMATIC SYMPTOMS

Posttraumatic headache

Posttraumatic headache is the most common sequela of concussion.²² Surprisingly, it is more common after concussion than after moderate or severe traumatic brain injury.²³ A prior history of headache, particularly migraine, is a known risk factor for development of posttraumatic headache.²⁴

Posttraumatic headache is usually further defined by headache type using the International Classification of Headache Disorders criteria (www.ichd-3.org). Migraine or probable migraine is the most common type of posttraumatic headache; tension headache is less common.²⁵

Analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) are often used initially by patients to treat posttraumatic headache. One study found that 70% of patients used acetaminophen or an NSAID.²⁶

Treating early with effective therapy is the most important tenet of posttraumatic headache treatment, since 80% of those who self-treat have incomplete relief, and almost all of them are using over-the-counter products.²⁷ Overuse of over-the-counter abortive medications can lead to medication overuse headache, also known as rebound headache, thus complicating the treatment of posttraumatic headache.²⁶

Earlier treatment with a preventive medication can often limit the need for and overuse of over-the-counter analgesics and can minimize the occurrence of subsequent medication overuse headache. However, in pediatric populations, nonpharmacologic interventions such as rest and sleep hygiene are typically used first, then medications after 4 to 6 weeks if this is ineffective.

A number of medications have been studied for prophylactic treatment of posttraumatic headache, including topiramate, amitriptyline, and divalproex sodium,^28–30 but there is little compelling evidence for use of one over the other. If posttraumatic headache is migrainous, beta-blockers, calcium-channel blockers, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibtors, and gabapentin are other prophylactic medication options under the appropriate circumstances.^27,31,32 In adults, we have clinically had success with nortriptyline 20 mg or gabapentin 300 mg at night as an initial prophylactic headache medication, increasing as tolerated or until pain is controlled, though there are no high-quality data to guide this decision.

The ideal prophylactic medication depends on headache type, patient tolerance, comorbidities, allergies, and medication sensitivities. Gabapentin, amitriptyline, and nortriptyline can produce sedation, which can help those suffering from sleep disturbance.

If a provider is not comfortable prescribing these medications or doesn’t prescribe them regularly, the patient should be referred to a concussion or headache specialist more familiar with their use.

In some patients, even some athletes, headache may be related to a cervical strain injury—whiplash—that should be treated with an NSAID (or acetaminophen), perhaps with a short course of a muscle relaxant in adults, and with physical therapy.³²

Some patients have chronic headache despite oral medications.²⁶ Therefore, alternatives to oral medications and complementary therapies should be considered. Especially for protracted cases requiring more complicated headache management or injectable treatments, patients should be referred to a pain clinic, headache specialist, or concussion specialist.

Dizziness is also common after concussion. But what the patient means by dizziness requires a little probing. Some have paroxysms of vertigo. This typically represents a peripheral vestibular injury, usually benign paroxysmal positional vertigo. The latter can be elicited with a Hallpike maneuver and treated in the office with the Epley maneuver.³³

Usually, dizziness is a subjective sense of poor coordination, gait instability, or dysequilibrium. Patients may also complain of associated nausea and motion sensitivity. This may all be secondary to a mechanism in the middle or inner ear or the brain. Patients should be encouraged to begin movement—gradually and safely—to help the vestibular system accommodate, which it will do with gradual stimulation. It usually resolves spontaneously.

Specific treatment is unfortunately limited. There is no established benefit from vestibular suppressants such as meclizine. Vestibular rehabilitation may accelerate improvement and decrease symptoms.³³ Referral for a comprehensive balance assessment or to vestibular therapy (a subset of physical therapy) should be considered and is something we typically undertake in our clinic if there is no recovery from dizziness 4 to 6 weeks after the concussion.

Visual symptoms can contribute to dizziness. Convergence spasm or convergence insufficiency (both related to muscle spasm of the eye) can occur after concussion, with some studies estimating that up to 69% of patients have these symptoms.³⁴ This can interfere with visual tracking and contribute to a feeling of dysequilibrium.³⁴ Referral to a concussion specialist or vestibular rehabilitation physical therapist can be helpful in treating this issue if it does not resolve spontaneously.

Orthostasis and lightheadedness also contribute to dizziness and are associated with cerebrovascular autoregulation. Available data suggest that dysregulation of neurovascular coupling, cerebral vasoreactivity, and cerebral autoregulation contribute to some of the chronic symptoms of concussion, including dizziness. A gradual return to exercise may help regulate cerebral blood flow and improve this type of dizziness.³⁵

Sleep disturbance

Sleep disturbance is common after concussion, but the form is variable: insomnia, excessive daytime somnolence, and alteration of the sleep-wake cycle are all seen and may themselves affect recovery.³⁶

Sleep hygiene education should be the first intervention for postconcussive sleep issues. For example, the patient should be encouraged to do the following:

• Minimize “screen time” an hour before going to bed: cell phone, tablet, and computer screens emit a wavelength of light that suppresses endogenous melatonin release^37,38
• Go to bed and wake up at the same time each day
• Minimize or avoid caffeine, nicotine, and alcohol
• Avoid naps.³⁹

Melatonin is a safe and effective treatment that could be added.⁴⁰ In addition, some studies suggest that melatonin may improve recovery from traumatic brain injury.^41,42

Mild exercise (to below the threshold of causing or exacerbating symptoms) may also improve sleep quality.

Amitriptyline or nortriptyline may reduce headache frequency and intensity and also help treat insomnia.

Trazodone is recommended by some as a first-line agent,³⁹ but we usually reserve it for protracted insomnia refractory to the above treatments.

Benzodiazepines should be avoided, as they reduce arousal, impair cognition, and exacerbate motor impairments.⁴³

Emotional symptoms

Acute-onset anxiety or depression often occurs after concussion.^44,45 There is abundant evidence that emotional effects of injury may be the most significant factor in recovery.⁴⁶ A preinjury history of anxiety may be a prognostic factor.⁹ Patients with a history of anxiety or depression are more likely to develop emotional symptoms after a concussion, but emotional problems may develop in any patient after a concussion.^47,48

The circumstances under which an injury is sustained may be traumatic (eg, car accident, assault), leading to an acute stress reaction or disorder and, if untreated, may result in a more chronic condition—posttraumatic stress disorder. Moreover, the injury and subsequent symptoms may have repercussions in many aspects of the patient’s life, leading to further psychologic stress (eg, loss of wages or the inability to handle normal work, school, and family responsibilities).

Referral to a therapist trained in skills-based psychotherapy (eg, cognitive-behavioral therapy, exposure-based treatment) is often helpful.

Pharmacologic treatment can be a useful adjunct. Several studies have shown that selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants may improve depression after concussion.⁴⁹ The prescription of antidepressants, however, is best left to providers with experience in treating anxiety and depression.

As with sleep disorders after concussion, benzodiazepines should be avoided, as they can impair cognition.⁴³

Cognitive problems

Cognitive problems are also common after concussion. Patients complain about everyday experiences of forgetfulness, distractibility, loss of concentration, and mental fatigue. Although patients often subjectively perceive these symptoms as quite limiting, the impairments can be difficult to demonstrate in office testing.

A program of gradual increase in mental activity, parallel to recovery of physical capacity, should be undertaken. Most patients make a gradual recovery within a few weeks.⁵⁰

When cognitive symptoms cause significant school or vocational problems or become persistent, patients should be referred to a specialty clinic. As with most of the consequences of concussion, there are few established treatments. When cognitive difficulties persist, it is important to consider the complications of concussion mentioned above: headache, pain, sleep disturbance, and anxiety, all of which may cause subjective cognitive problems and are treatable.

If cognitive symptoms are prolonged despite improvement of other issues like headache and sleep disturbance, a low-dose stimulant medication such as amphetamine salts or methylphenidate may be useful for symptoms of poor attention.⁴⁹ They should be only a temporary measure after concussion to carry the patient through a cognitively challenging period, unless there was a history of attention-deficit disorder before the injury. A variety of other agents, including amantadine,⁵¹ have been proposed based on limited studies; all are off-label uses. Before considering these types of interventions, referral to a specialist or a specialty program would be appropriate.

With the interventions suggested above, most patients with concussion have a resolution of symptoms and can return to preinjury levels of performance. But some have prolonged symptoms and sequelae. Approximately 10% of athletes have persistent signs and symptoms of concussion beyond 2 weeks. If concussion is not sport-related, most patients recover completely within the first 3 months, but up to 33% may have symptoms beyond that.⁵²

Four types of patients have persistent symptoms:

Patients who sustained a high-force mechanism of injury. These patients simply need more time and accommodation.

Patients who sustained multiple concussions. These patients may also need more time and accommodation.

Patients with an underlying neurologic condition, recognized prior to injury or not, may have delayed or incomplete recovery. Even aging may be an “underlying condition” in concussion.

Patients whose symptoms from an apparently single mild concussion do not resolve despite appropriate treatments may have identifiable factors, but intractable pain (usually headache) or significant emotional disturbance or both are common. Once established and persistent, this is difficult to treat. Referral to a specialty practice is appropriate, but even in that setting effective treatment may be elusive.

PATIENT EDUCATION

Most important for patient education is reassurance. Ultimately, concussion is a self-limited phenomenon, and reinforcing this is helpful for patients. If concussion is not sport-related, most patients recover completely within 3 months.

The next important tenet in patient education is that they should rest for 3 to 5 days, then resume gradual physical and cognitive activities. If resuming activities too soon results in symptoms, then they should rest for a day and gradually resume activity. If their recovery is prolonged (ie, longer than 6 weeks), they likely need to be referred to a concussion specialist.

We well recall, back in the day, getting our “bell rung” from some form of sports-related head contact. If we could count the coach’s fingers clearly, run fast and straight, and know the plays, we could happily go back into the game. There was little additional thought given to short-term or lasting effects. I recall hearing tales from my grandfather, a boxing enthusiast, of retired punch-drunk fighters working as bouncers and greeters at sports-focused restaurants and clubs. I certainly didn’t draw any link to a few episodes of personally feeling spacey or dizzy after playing football.

But now, as parents, we are all highly tuned in to the issue of wrongly minimized “minor” head contact and concussion in our children playing sports. There is a growing research-based understanding of the mechanisms of concussion, which remains a clinical syndrome diagnosed on the basis of symptoms and sometimes subtle objective findings that occur in the appropriate environmental context. Intracranial brain impact sets the stage for locally spreading firing of neurons outside their usual pattern. This can result in a diffuse jamming of some normal electrochemical pathways of cognitive function, as well as create additional mismatch between neuronal metabolic needs and the local blood flow providing oxygen and nutrients. This disruption in autoregulation of blood flow sets the stage for enhanced brain sensitivity to any second injurious event, even a minimal one. Hence the aggressive implementation of enforced rest and recovery time for athletes and others with concussion.

It is critical to realize that the patient may not have had a loss of consciousness. Equally important is to consider the need for imaging and protection of patients who are not recovering as expected in 7 to 10 days, as well as for initial imaging of those with severe head impact or baseline neurologic disease, the aged, and those on anticoagulation.

We well recall, back in the day, getting our “bell rung” from some form of sports-related head contact. If we could count the coach’s fingers clearly, run fast and straight, and know the plays, we could happily go back into the game. There was little additional thought given to short-term or lasting effects. I recall hearing tales from my grandfather, a boxing enthusiast, of retired punch-drunk fighters working as bouncers and greeters at sports-focused restaurants and clubs. I certainly didn’t draw any link to a few episodes of personally feeling spacey or dizzy after playing football.

But now, as parents, we are all highly tuned in to the issue of wrongly minimized “minor” head contact and concussion in our children playing sports. There is a growing research-based understanding of the mechanisms of concussion, which remains a clinical syndrome diagnosed on the basis of symptoms and sometimes subtle objective findings that occur in the appropriate environmental context. Intracranial brain impact sets the stage for locally spreading firing of neurons outside their usual pattern. This can result in a diffuse jamming of some normal electrochemical pathways of cognitive function, as well as create additional mismatch between neuronal metabolic needs and the local blood flow providing oxygen and nutrients. This disruption in autoregulation of blood flow sets the stage for enhanced brain sensitivity to any second injurious event, even a minimal one. Hence the aggressive implementation of enforced rest and recovery time for athletes and others with concussion.

It is critical to realize that the patient may not have had a loss of consciousness. Equally important is to consider the need for imaging and protection of patients who are not recovering as expected in 7 to 10 days, as well as for initial imaging of those with severe head impact or baseline neurologic disease, the aged, and those on anticoagulation.

We well recall, back in the day, getting our “bell rung” from some form of sports-related head contact. If we could count the coach’s fingers clearly, run fast and straight, and know the plays, we could happily go back into the game. There was little additional thought given to short-term or lasting effects. I recall hearing tales from my grandfather, a boxing enthusiast, of retired punch-drunk fighters working as bouncers and greeters at sports-focused restaurants and clubs. I certainly didn’t draw any link to a few episodes of personally feeling spacey or dizzy after playing football.

But now, as parents, we are all highly tuned in to the issue of wrongly minimized “minor” head contact and concussion in our children playing sports. There is a growing research-based understanding of the mechanisms of concussion, which remains a clinical syndrome diagnosed on the basis of symptoms and sometimes subtle objective findings that occur in the appropriate environmental context. Intracranial brain impact sets the stage for locally spreading firing of neurons outside their usual pattern. This can result in a diffuse jamming of some normal electrochemical pathways of cognitive function, as well as create additional mismatch between neuronal metabolic needs and the local blood flow providing oxygen and nutrients. This disruption in autoregulation of blood flow sets the stage for enhanced brain sensitivity to any second injurious event, even a minimal one. Hence the aggressive implementation of enforced rest and recovery time for athletes and others with concussion.

It is critical to realize that the patient may not have had a loss of consciousness. Equally important is to consider the need for imaging and protection of patients who are not recovering as expected in 7 to 10 days, as well as for initial imaging of those with severe head impact or baseline neurologic disease, the aged, and those on anticoagulation.

Click here to download the PDF.

Click here to download the PDF.

Click here to download the PDF.

BOSTON—Among patients with primary restless legs syndrome (RLS) and without a history of psychiatric disorders, patients who receive de novo dopamine agonist treatment are approximately twice as likely to subsequently develop a mental disorder as those who do not receive dopamine agonist treatment, according to a large-scale retrospective study presented at the 31st Annual Meeting of the Associated Professional Sleep Societies.

Previous research has demonstrated an increased risk of mental disorders among patients with Parkinson’s disease who are treated with dopamine agonists. Many patients with RLS are also treated with dopamine agonists, although at lower doses than patients with Parkinson’s disease. Given these lower doses, clinicians assumed that the risk of dopamine agonist-induced mental disorders in RLS would be small. Clinical case studies suggest a higher-than-anticipated risk, however.

An Examination of Claims Data

To investigate whether dopamine agonists increase the risk of developing mental disorders in patients with RLS, Cheryl Hankin, PhD, President and Chief Scientific Officer of BioMedEcon, a health economics and outcomes research firm in Moss Beach, California, and colleagues examined Truven MarketScan Commercial and Medicare Supplemental databases of claims filed between July 1, 2008, and December 31, 2014. From a pool of 539,399 patients with a diagnosis of RLS, investigators identified adults with two or more years of claims data preceding and following their index RLS diagnosis dates.

Patients were excluded from the analysis if, in the two or more years preceding RLS diagnosis, they received a diagnosis of mental disorder or filled a prescription for an antidepressant or antipsychotic. Also excluded were patients who filled a prescription for a dopamine agonist in the two or more years preceding RLS diagnosis. Patients who were ever diagnosed with Parkinson’s disease, kidney disease, iron deficiency, or pregnancy were assumed to have secondary RLS and were also excluded.

The investigators identified 5,419 eligible participants. Of this group, 1,649 patients received dopamine agonists after RLS diagnosis. Specifically, 571 participants received pramipexole, 915 received ropinirole, and 163 received both. Approximately 65% of patients were female. Patients residing in the Northeast were significantly less likely to receive dopamine agonists, compared with patients residing in the Midwest or the South. The investigators found no significant differences in treatment status by comorbid illness burden or by sex. The investigators also found no significant differences in demographic characteristics between patients receiving pramipexole and those receiving ropinirole.

Risk Was Significantly Greater in Patients Receiving Dopamine Agonist

Next, from this pool of eligible subjects, the researchers matched 1,080 patients treated with dopamine agonists with 1,080 dopamine agonist-naïve patients on sex, age at RLS diagnosis, region, employment, and illness burden. Dr. Hankin and colleagues found a significant increase in mental disorder diagnoses (eg, bipolar disorder, anxiety, depression, and substance abuse) among patients treated with dopamine agonists, compared with dopamine agonist-naïve patients. Among patients receiving dopamine agonists, the odds ratio for severe mental disorder (eg, psychoses and bipolar disorder) was 2.2, the odds ratio for moderate to severe mental disorder (eg, posttraumatic stress disorder and major depression) was 1.8, and the odds ratio for mild mental disorder (eg, anxiety disorders) was 1.9, compared with dopamine agonist-naïve patients.

“This is the first large-scale, real-world, claims-based study to examine the association between treatment of RLS with dopamine agonists and the development of psychiatric adverse events. Our findings are compelling, but need to be replicated in other patient populations,” said Dr. Hankin.

“Our retrospective analysis required careful consideration of matching,” said Daniel On-Fai Lee, MD, Clinical Professor of Neurology at the University of Kentucky College of Medicine in Lexington, who collaborated on the study. Although the investigators took care to match participants and to remove cases of secondary RLS from the analysis, they may have inadvertently overlooked one or more important matching variables that could affect the outcome, he added.

Arbor Pharmaceuticals provided funding for the study, but did not influence its methodology, analysis, results, or conclusion, said Dr. Lee.

—Erik Greb

Suggested Reading

Sierra M, Carnicella S, Strafella AP, et al. Apathy and impulse control disorders: yin & yang of dopamine dependent behaviors. J Parkinsons Dis. 2015;5(3):625-636.

Wilt TJ, MacDonald R, Ouellette J, et al. Pharmacologic therapy for primary restless legs syndrome: a systematic review and meta-analysis. JAMA Intern Med. 2013;173(7):496-505.

BOSTON—Among patients with primary restless legs syndrome (RLS) and without a history of psychiatric disorders, patients who receive de novo dopamine agonist treatment are approximately twice as likely to subsequently develop a mental disorder as those who do not receive dopamine agonist treatment, according to a large-scale retrospective study presented at the 31st Annual Meeting of the Associated Professional Sleep Societies.

Previous research has demonstrated an increased risk of mental disorders among patients with Parkinson’s disease who are treated with dopamine agonists. Many patients with RLS are also treated with dopamine agonists, although at lower doses than patients with Parkinson’s disease. Given these lower doses, clinicians assumed that the risk of dopamine agonist-induced mental disorders in RLS would be small. Clinical case studies suggest a higher-than-anticipated risk, however.

An Examination of Claims Data

To investigate whether dopamine agonists increase the risk of developing mental disorders in patients with RLS, Cheryl Hankin, PhD, President and Chief Scientific Officer of BioMedEcon, a health economics and outcomes research firm in Moss Beach, California, and colleagues examined Truven MarketScan Commercial and Medicare Supplemental databases of claims filed between July 1, 2008, and December 31, 2014. From a pool of 539,399 patients with a diagnosis of RLS, investigators identified adults with two or more years of claims data preceding and following their index RLS diagnosis dates.

Patients were excluded from the analysis if, in the two or more years preceding RLS diagnosis, they received a diagnosis of mental disorder or filled a prescription for an antidepressant or antipsychotic. Also excluded were patients who filled a prescription for a dopamine agonist in the two or more years preceding RLS diagnosis. Patients who were ever diagnosed with Parkinson’s disease, kidney disease, iron deficiency, or pregnancy were assumed to have secondary RLS and were also excluded.

The investigators identified 5,419 eligible participants. Of this group, 1,649 patients received dopamine agonists after RLS diagnosis. Specifically, 571 participants received pramipexole, 915 received ropinirole, and 163 received both. Approximately 65% of patients were female. Patients residing in the Northeast were significantly less likely to receive dopamine agonists, compared with patients residing in the Midwest or the South. The investigators found no significant differences in treatment status by comorbid illness burden or by sex. The investigators also found no significant differences in demographic characteristics between patients receiving pramipexole and those receiving ropinirole.

Risk Was Significantly Greater in Patients Receiving Dopamine Agonist

Next, from this pool of eligible subjects, the researchers matched 1,080 patients treated with dopamine agonists with 1,080 dopamine agonist-naïve patients on sex, age at RLS diagnosis, region, employment, and illness burden. Dr. Hankin and colleagues found a significant increase in mental disorder diagnoses (eg, bipolar disorder, anxiety, depression, and substance abuse) among patients treated with dopamine agonists, compared with dopamine agonist-naïve patients. Among patients receiving dopamine agonists, the odds ratio for severe mental disorder (eg, psychoses and bipolar disorder) was 2.2, the odds ratio for moderate to severe mental disorder (eg, posttraumatic stress disorder and major depression) was 1.8, and the odds ratio for mild mental disorder (eg, anxiety disorders) was 1.9, compared with dopamine agonist-naïve patients.

“This is the first large-scale, real-world, claims-based study to examine the association between treatment of RLS with dopamine agonists and the development of psychiatric adverse events. Our findings are compelling, but need to be replicated in other patient populations,” said Dr. Hankin.

“Our retrospective analysis required careful consideration of matching,” said Daniel On-Fai Lee, MD, Clinical Professor of Neurology at the University of Kentucky College of Medicine in Lexington, who collaborated on the study. Although the investigators took care to match participants and to remove cases of secondary RLS from the analysis, they may have inadvertently overlooked one or more important matching variables that could affect the outcome, he added.

Arbor Pharmaceuticals provided funding for the study, but did not influence its methodology, analysis, results, or conclusion, said Dr. Lee.

—Erik Greb

Suggested Reading

Sierra M, Carnicella S, Strafella AP, et al. Apathy and impulse control disorders: yin & yang of dopamine dependent behaviors. J Parkinsons Dis. 2015;5(3):625-636.

Wilt TJ, MacDonald R, Ouellette J, et al. Pharmacologic therapy for primary restless legs syndrome: a systematic review and meta-analysis. JAMA Intern Med. 2013;173(7):496-505.

BOSTON—Among patients with primary restless legs syndrome (RLS) and without a history of psychiatric disorders, patients who receive de novo dopamine agonist treatment are approximately twice as likely to subsequently develop a mental disorder as those who do not receive dopamine agonist treatment, according to a large-scale retrospective study presented at the 31st Annual Meeting of the Associated Professional Sleep Societies.

Previous research has demonstrated an increased risk of mental disorders among patients with Parkinson’s disease who are treated with dopamine agonists. Many patients with RLS are also treated with dopamine agonists, although at lower doses than patients with Parkinson’s disease. Given these lower doses, clinicians assumed that the risk of dopamine agonist-induced mental disorders in RLS would be small. Clinical case studies suggest a higher-than-anticipated risk, however.

An Examination of Claims Data

To investigate whether dopamine agonists increase the risk of developing mental disorders in patients with RLS, Cheryl Hankin, PhD, President and Chief Scientific Officer of BioMedEcon, a health economics and outcomes research firm in Moss Beach, California, and colleagues examined Truven MarketScan Commercial and Medicare Supplemental databases of claims filed between July 1, 2008, and December 31, 2014. From a pool of 539,399 patients with a diagnosis of RLS, investigators identified adults with two or more years of claims data preceding and following their index RLS diagnosis dates.

Patients were excluded from the analysis if, in the two or more years preceding RLS diagnosis, they received a diagnosis of mental disorder or filled a prescription for an antidepressant or antipsychotic. Also excluded were patients who filled a prescription for a dopamine agonist in the two or more years preceding RLS diagnosis. Patients who were ever diagnosed with Parkinson’s disease, kidney disease, iron deficiency, or pregnancy were assumed to have secondary RLS and were also excluded.

The investigators identified 5,419 eligible participants. Of this group, 1,649 patients received dopamine agonists after RLS diagnosis. Specifically, 571 participants received pramipexole, 915 received ropinirole, and 163 received both. Approximately 65% of patients were female. Patients residing in the Northeast were significantly less likely to receive dopamine agonists, compared with patients residing in the Midwest or the South. The investigators found no significant differences in treatment status by comorbid illness burden or by sex. The investigators also found no significant differences in demographic characteristics between patients receiving pramipexole and those receiving ropinirole.

Risk Was Significantly Greater in Patients Receiving Dopamine Agonist

Next, from this pool of eligible subjects, the researchers matched 1,080 patients treated with dopamine agonists with 1,080 dopamine agonist-naïve patients on sex, age at RLS diagnosis, region, employment, and illness burden. Dr. Hankin and colleagues found a significant increase in mental disorder diagnoses (eg, bipolar disorder, anxiety, depression, and substance abuse) among patients treated with dopamine agonists, compared with dopamine agonist-naïve patients. Among patients receiving dopamine agonists, the odds ratio for severe mental disorder (eg, psychoses and bipolar disorder) was 2.2, the odds ratio for moderate to severe mental disorder (eg, posttraumatic stress disorder and major depression) was 1.8, and the odds ratio for mild mental disorder (eg, anxiety disorders) was 1.9, compared with dopamine agonist-naïve patients.

“This is the first large-scale, real-world, claims-based study to examine the association between treatment of RLS with dopamine agonists and the development of psychiatric adverse events. Our findings are compelling, but need to be replicated in other patient populations,” said Dr. Hankin.

“Our retrospective analysis required careful consideration of matching,” said Daniel On-Fai Lee, MD, Clinical Professor of Neurology at the University of Kentucky College of Medicine in Lexington, who collaborated on the study. Although the investigators took care to match participants and to remove cases of secondary RLS from the analysis, they may have inadvertently overlooked one or more important matching variables that could affect the outcome, he added.

Arbor Pharmaceuticals provided funding for the study, but did not influence its methodology, analysis, results, or conclusion, said Dr. Lee.

—Erik Greb

Suggested Reading

Sierra M, Carnicella S, Strafella AP, et al. Apathy and impulse control disorders: yin & yang of dopamine dependent behaviors. J Parkinsons Dis. 2015;5(3):625-636.

Wilt TJ, MacDonald R, Ouellette J, et al. Pharmacologic therapy for primary restless legs syndrome: a systematic review and meta-analysis. JAMA Intern Med. 2013;173(7):496-505.

BOSTON—Objective sleep duration moderates the probability of remission among patients with comorbid depression and insomnia, according to research presented at the 31st Annual Meeting of the Associated Professional Sleep Societies. Sleep durations of greater than five to six hours increase the likelihood that these patients will achieve insomnia remission with cognitive behavioral therapy for insomnia (CBT-I), but do not affect the likelihood of depression remission. Sleep durations of seven or more hours optimize the likelihood of insomnia remission and depression remission in response to CBT-I.

In a 2015 consensus statement, the Sleep Research Society recommended seven or more hours of sleep per night for adults younger than 60. Investigations by Vgontzas and colleagues indicate that sleep durations of less than five hours and less than six hours are associated with increased morbidity and poor treatment response among patients with insomnia. “We wanted to know what [sleep-duration] cutoffs … might be better predictors of eventual insomnia and depression remission through treatment,” said Jack Edinger, PhD, Professor of Medicine at National Jewish Health in Denver.

An Analysis of the TRIAD Study

Dr. Edinger and colleagues conducted a secondary analysis of the TRIAD study, which examined whether combined treatment of depression and insomnia improves depression and sleep outcomes in participants with both disorders. Eligible participants met Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria for major depression and primary insomnia, had a Hamilton Rating Scale for Depression (HAMD-17) score of 16 or greater, and had an Insomnia Severity Index (ISI) score of 11 or greater. People who had had psychotherapy in the previous four months, or had failed or could not tolerate previous adequate trials of the study medications, were excluded. Participants completed one night of baseline polysomnography before entering the treatment phase of the study.

The study population included 104 participants (75 women) with a mean age of 47. Mean baseline HAMD-17 score was 22, and mean baseline ISI score was 20.6. All participants received antidepressant medication (ie, citalopram, sertraline, or venlafaxine). Patients were randomized to CBT-I or sham (ie, a pseudo desensitization condition with sleep education). The investigators assessed participants biweekly with the HAMD-17 and the ISI. The treatment period lasted for 16 weeks.

CBT-I Provided Benefits

Participants with five or more hours of sleep were more likely to respond to CBT-I than participants with fewer than five hours of sleep. Among participants with sleep duration of five or more hours, insomnia remission was more likely with CBT-I than with the control condition. The five-hour cutoff had no association with depression remission.

Among participants with six or more hours of sleep, those who received CBT-I were more likely to achieve insomnia remission than controls. The six-hour cutoff did not affect the likelihood of depression remission, however.

Among participants with seven or more hours of sleep, those randomized to CBT-I were more likely to achieve insomnia remission and depression remission than controls.

“More research is needed to determine how best to achieve depression remission in those patients with less than seven hours of objective sleep duration prior to starting treatment,” Dr. Edinger concluded.

—Erik Greb

Suggested Reading

Bathgate CJ, Edinger JD, Krystal AD. Insomnia patients with objective short sleep duration have a blunted response to cognitive behavioral therapy for insomnia. Sleep. 2017;40(1).

Vgontzas AN, Liao D, Bixler EO, et al. Insomnia with objective short sleep duration is associated with a high risk for hypertension. Sleep. 2009;32(4):491-497.

Watson NF, Badr MS, Belenky G, et al. Recommended amount of sleep for a healthy adult: A joint consensus statement of the American Academy of Sleep Medicine and Sleep Research Society. Sleep. 2015;38(6):843-844.

BOSTON—Objective sleep duration moderates the probability of remission among patients with comorbid depression and insomnia, according to research presented at the 31st Annual Meeting of the Associated Professional Sleep Societies. Sleep durations of greater than five to six hours increase the likelihood that these patients will achieve insomnia remission with cognitive behavioral therapy for insomnia (CBT-I), but do not affect the likelihood of depression remission. Sleep durations of seven or more hours optimize the likelihood of insomnia remission and depression remission in response to CBT-I.

In a 2015 consensus statement, the Sleep Research Society recommended seven or more hours of sleep per night for adults younger than 60. Investigations by Vgontzas and colleagues indicate that sleep durations of less than five hours and less than six hours are associated with increased morbidity and poor treatment response among patients with insomnia. “We wanted to know what [sleep-duration] cutoffs … might be better predictors of eventual insomnia and depression remission through treatment,” said Jack Edinger, PhD, Professor of Medicine at National Jewish Health in Denver.

An Analysis of the TRIAD Study

Dr. Edinger and colleagues conducted a secondary analysis of the TRIAD study, which examined whether combined treatment of depression and insomnia improves depression and sleep outcomes in participants with both disorders. Eligible participants met Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria for major depression and primary insomnia, had a Hamilton Rating Scale for Depression (HAMD-17) score of 16 or greater, and had an Insomnia Severity Index (ISI) score of 11 or greater. People who had had psychotherapy in the previous four months, or had failed or could not tolerate previous adequate trials of the study medications, were excluded. Participants completed one night of baseline polysomnography before entering the treatment phase of the study.

The study population included 104 participants (75 women) with a mean age of 47. Mean baseline HAMD-17 score was 22, and mean baseline ISI score was 20.6. All participants received antidepressant medication (ie, citalopram, sertraline, or venlafaxine). Patients were randomized to CBT-I or sham (ie, a pseudo desensitization condition with sleep education). The investigators assessed participants biweekly with the HAMD-17 and the ISI. The treatment period lasted for 16 weeks.

CBT-I Provided Benefits

Participants with five or more hours of sleep were more likely to respond to CBT-I than participants with fewer than five hours of sleep. Among participants with sleep duration of five or more hours, insomnia remission was more likely with CBT-I than with the control condition. The five-hour cutoff had no association with depression remission.

Among participants with six or more hours of sleep, those who received CBT-I were more likely to achieve insomnia remission than controls. The six-hour cutoff did not affect the likelihood of depression remission, however.

Among participants with seven or more hours of sleep, those randomized to CBT-I were more likely to achieve insomnia remission and depression remission than controls.

“More research is needed to determine how best to achieve depression remission in those patients with less than seven hours of objective sleep duration prior to starting treatment,” Dr. Edinger concluded.

—Erik Greb

Suggested Reading

Bathgate CJ, Edinger JD, Krystal AD. Insomnia patients with objective short sleep duration have a blunted response to cognitive behavioral therapy for insomnia. Sleep. 2017;40(1).

Vgontzas AN, Liao D, Bixler EO, et al. Insomnia with objective short sleep duration is associated with a high risk for hypertension. Sleep. 2009;32(4):491-497.

Watson NF, Badr MS, Belenky G, et al. Recommended amount of sleep for a healthy adult: A joint consensus statement of the American Academy of Sleep Medicine and Sleep Research Society. Sleep. 2015;38(6):843-844.

BOSTON—Objective sleep duration moderates the probability of remission among patients with comorbid depression and insomnia, according to research presented at the 31st Annual Meeting of the Associated Professional Sleep Societies. Sleep durations of greater than five to six hours increase the likelihood that these patients will achieve insomnia remission with cognitive behavioral therapy for insomnia (CBT-I), but do not affect the likelihood of depression remission. Sleep durations of seven or more hours optimize the likelihood of insomnia remission and depression remission in response to CBT-I.

In a 2015 consensus statement, the Sleep Research Society recommended seven or more hours of sleep per night for adults younger than 60. Investigations by Vgontzas and colleagues indicate that sleep durations of less than five hours and less than six hours are associated with increased morbidity and poor treatment response among patients with insomnia. “We wanted to know what [sleep-duration] cutoffs … might be better predictors of eventual insomnia and depression remission through treatment,” said Jack Edinger, PhD, Professor of Medicine at National Jewish Health in Denver.

An Analysis of the TRIAD Study

Dr. Edinger and colleagues conducted a secondary analysis of the TRIAD study, which examined whether combined treatment of depression and insomnia improves depression and sleep outcomes in participants with both disorders. Eligible participants met Diagnostic and Statistical Manual of Mental Disorders (4th ed.) criteria for major depression and primary insomnia, had a Hamilton Rating Scale for Depression (HAMD-17) score of 16 or greater, and had an Insomnia Severity Index (ISI) score of 11 or greater. People who had had psychotherapy in the previous four months, or had failed or could not tolerate previous adequate trials of the study medications, were excluded. Participants completed one night of baseline polysomnography before entering the treatment phase of the study.

The study population included 104 participants (75 women) with a mean age of 47. Mean baseline HAMD-17 score was 22, and mean baseline ISI score was 20.6. All participants received antidepressant medication (ie, citalopram, sertraline, or venlafaxine). Patients were randomized to CBT-I or sham (ie, a pseudo desensitization condition with sleep education). The investigators assessed participants biweekly with the HAMD-17 and the ISI. The treatment period lasted for 16 weeks.

CBT-I Provided Benefits

Participants with five or more hours of sleep were more likely to respond to CBT-I than participants with fewer than five hours of sleep. Among participants with sleep duration of five or more hours, insomnia remission was more likely with CBT-I than with the control condition. The five-hour cutoff had no association with depression remission.

Among participants with six or more hours of sleep, those who received CBT-I were more likely to achieve insomnia remission than controls. The six-hour cutoff did not affect the likelihood of depression remission, however.

Among participants with seven or more hours of sleep, those randomized to CBT-I were more likely to achieve insomnia remission and depression remission than controls.

“More research is needed to determine how best to achieve depression remission in those patients with less than seven hours of objective sleep duration prior to starting treatment,” Dr. Edinger concluded.

—Erik Greb

Suggested Reading

Bathgate CJ, Edinger JD, Krystal AD. Insomnia patients with objective short sleep duration have a blunted response to cognitive behavioral therapy for insomnia. Sleep. 2017;40(1).

Vgontzas AN, Liao D, Bixler EO, et al. Insomnia with objective short sleep duration is associated with a high risk for hypertension. Sleep. 2009;32(4):491-497.

Watson NF, Badr MS, Belenky G, et al. Recommended amount of sleep for a healthy adult: A joint consensus statement of the American Academy of Sleep Medicine and Sleep Research Society. Sleep. 2015;38(6):843-844.

Light therapy may reduce excessive daytime sleepiness and improve sleep quality in patients with Parkinson’s disease, according to trial results published in the April issue of JAMA Neurology. The treatment modality is well tolerated, widely available, and “relatively easy to prescribe and incorporate into a clinical practice,” said Aleksandar Videnovic, MD, a neurologist at Massachusetts General Hospital in Boston, and colleagues.

Impaired sleep and alertness are common nonmotor manifestations of Parkinson’s disease with limited treatment options. Patients’ sleep disturbances have been attributed to Parkinson’s disease symptoms, adverse medication effects, and neurodegeneration of central sleep regulatory areas. Altered circadian rhythms also may play a role. Supplemental exposure to bright light improves sleep quality and daytime vigilance in healthy older people and patients with dementia, but the treatment modality has not been studied systematically in patients with Parkinson’s disease, the researchers said.

One-Hour Treatment Intervals

To determine the safety and efficacy of light therapy on excessive daytime sleepiness associated with Parkinson’s disease, Dr. Videnovic and colleagues conducted a randomized, placebo-controlled trial.

They enrolled 31 patients with Parkinson’s disease and excessive daytime sleepiness (ie, an Epworth Sleepiness Scale score of 12 or greater). Patients were receiving stable dopaminergic therapy and did not have cognitive impairment or a primary sleep disorder. Investigators randomized participants 1:1 to receive bright light therapy (10,000 lux) or a control condition of dim-red light therapy (less than 300 lux). After a two-week baseline phase, participants received light therapy in one-hour intervals twice daily—in the morning (between 9 am and 11 am) and in the afternoon (between 5 pm and 7 pm)—for 14 days. The primary outcome measure was change in Epworth Sleepiness Scale score from baseline. During the study, each patient wore an actigraphy monitor and completed a daily sleep log and various other assessments.

During treatment, a light box was placed 86.4 cm away from the patient. Participants were instructed to sit quietly and not nap. They could listen to music or audiobooks.

The 31 patients (18 females) had an average age of about 63 (range, 32 to 77) and an average disease duration of about six years. Among patients who received bright light therapy, mean Epworth Sleepiness Scale score significantly improved from 15.81 at baseline to 11.19 post intervention. The improvement was significantly greater than that for patients in the control group, who had a mean Epworth Sleepiness Scale score of 15.47 at baseline and 13.67 post intervention.

Improvements in sleep quality, latency, and fragmentation were significantly greater in the bright light therapy group than in the control group. In both treatment arms, light therapy was associated with increased daily physical activity, as assessed by actigraphy, and reduced disease severity, as assessed by the Unified Parkinson’s Disease Rating Scale. Light therapy was not associated with significant changes in depression, anxiety, or quality of life.

In the active treatment group, one patient reported headache, and another patient reported sleepiness. One participant in the control group reported itchy eyes. The adverse events resolved spontaneously, and adherence to the study protocol was excellent, the researchers said.

Although improvement in the control arm may have been due to the placebo effect, it is also possible that “anchoring the light therapy to a strict twice-daily regimen provided means for structuring daily activities, which itself may be an interesting possible mechanism underlying the beneficial effects of … light therapy,” Dr. Videnovic and colleagues said. Future studies should address the optimal treatment parameters for light therapy in Parkinson’s disease, they added.

Whether light therapy produces direct alerting effects, influences the circadian system, or works through another mechanism is not clear. A limitation of the study was that light levels were not measured throughout the day, so patients in the control group could have received more light from other sources overall, compared with patients in the active treatment group, the investigators noted.

Chronobiologic Interventions

The study shows that chronobiologic interventions “can be used therapeutically in patients with Parkinson’s disease” and “introduce a new concept into the much-studied phenomenon of disturbed sleep and wakefulness in Parkinson’s disease,” said Birgit Högl, MD, of the Department of Neurology at the Medical University of Innsbruck in Austria, in an accompanying editorial. Although the study of chronobiology is complex, certain aspects of chronobiology can be “integrated into routine medical practice and improve outcomes for patients,” Dr. Högl said.

—Jake Remaly

Suggested Reading

Högl B. Circadian rhythms and chronotherapeutics-Underappreciated approach to improving sleep and wakefulness in Parkinson disease. JAMA Neurol. 2017;74(4):387-388.

Videnovic A, Klerman EB, Wang W, et al. Timed light therapy for sleep and daytime sleepiness associated with Parkinson disease: A randomized clinical trial. JAMA Neurol. 2017;74(4):411-418.

Light therapy may reduce excessive daytime sleepiness and improve sleep quality in patients with Parkinson’s disease, according to trial results published in the April issue of JAMA Neurology. The treatment modality is well tolerated, widely available, and “relatively easy to prescribe and incorporate into a clinical practice,” said Aleksandar Videnovic, MD, a neurologist at Massachusetts General Hospital in Boston, and colleagues.

Impaired sleep and alertness are common nonmotor manifestations of Parkinson’s disease with limited treatment options. Patients’ sleep disturbances have been attributed to Parkinson’s disease symptoms, adverse medication effects, and neurodegeneration of central sleep regulatory areas. Altered circadian rhythms also may play a role. Supplemental exposure to bright light improves sleep quality and daytime vigilance in healthy older people and patients with dementia, but the treatment modality has not been studied systematically in patients with Parkinson’s disease, the researchers said.

One-Hour Treatment Intervals

To determine the safety and efficacy of light therapy on excessive daytime sleepiness associated with Parkinson’s disease, Dr. Videnovic and colleagues conducted a randomized, placebo-controlled trial.

They enrolled 31 patients with Parkinson’s disease and excessive daytime sleepiness (ie, an Epworth Sleepiness Scale score of 12 or greater). Patients were receiving stable dopaminergic therapy and did not have cognitive impairment or a primary sleep disorder. Investigators randomized participants 1:1 to receive bright light therapy (10,000 lux) or a control condition of dim-red light therapy (less than 300 lux). After a two-week baseline phase, participants received light therapy in one-hour intervals twice daily—in the morning (between 9 am and 11 am) and in the afternoon (between 5 pm and 7 pm)—for 14 days. The primary outcome measure was change in Epworth Sleepiness Scale score from baseline. During the study, each patient wore an actigraphy monitor and completed a daily sleep log and various other assessments.

During treatment, a light box was placed 86.4 cm away from the patient. Participants were instructed to sit quietly and not nap. They could listen to music or audiobooks.

The 31 patients (18 females) had an average age of about 63 (range, 32 to 77) and an average disease duration of about six years. Among patients who received bright light therapy, mean Epworth Sleepiness Scale score significantly improved from 15.81 at baseline to 11.19 post intervention. The improvement was significantly greater than that for patients in the control group, who had a mean Epworth Sleepiness Scale score of 15.47 at baseline and 13.67 post intervention.

Improvements in sleep quality, latency, and fragmentation were significantly greater in the bright light therapy group than in the control group. In both treatment arms, light therapy was associated with increased daily physical activity, as assessed by actigraphy, and reduced disease severity, as assessed by the Unified Parkinson’s Disease Rating Scale. Light therapy was not associated with significant changes in depression, anxiety, or quality of life.

In the active treatment group, one patient reported headache, and another patient reported sleepiness. One participant in the control group reported itchy eyes. The adverse events resolved spontaneously, and adherence to the study protocol was excellent, the researchers said.

Although improvement in the control arm may have been due to the placebo effect, it is also possible that “anchoring the light therapy to a strict twice-daily regimen provided means for structuring daily activities, which itself may be an interesting possible mechanism underlying the beneficial effects of … light therapy,” Dr. Videnovic and colleagues said. Future studies should address the optimal treatment parameters for light therapy in Parkinson’s disease, they added.

Whether light therapy produces direct alerting effects, influences the circadian system, or works through another mechanism is not clear. A limitation of the study was that light levels were not measured throughout the day, so patients in the control group could have received more light from other sources overall, compared with patients in the active treatment group, the investigators noted.

Chronobiologic Interventions

The study shows that chronobiologic interventions “can be used therapeutically in patients with Parkinson’s disease” and “introduce a new concept into the much-studied phenomenon of disturbed sleep and wakefulness in Parkinson’s disease,” said Birgit Högl, MD, of the Department of Neurology at the Medical University of Innsbruck in Austria, in an accompanying editorial. Although the study of chronobiology is complex, certain aspects of chronobiology can be “integrated into routine medical practice and improve outcomes for patients,” Dr. Högl said.

—Jake Remaly

Suggested Reading

Högl B. Circadian rhythms and chronotherapeutics-Underappreciated approach to improving sleep and wakefulness in Parkinson disease. JAMA Neurol. 2017;74(4):387-388.

Videnovic A, Klerman EB, Wang W, et al. Timed light therapy for sleep and daytime sleepiness associated with Parkinson disease: A randomized clinical trial. JAMA Neurol. 2017;74(4):411-418.

Light therapy may reduce excessive daytime sleepiness and improve sleep quality in patients with Parkinson’s disease, according to trial results published in the April issue of JAMA Neurology. The treatment modality is well tolerated, widely available, and “relatively easy to prescribe and incorporate into a clinical practice,” said Aleksandar Videnovic, MD, a neurologist at Massachusetts General Hospital in Boston, and colleagues.

Impaired sleep and alertness are common nonmotor manifestations of Parkinson’s disease with limited treatment options. Patients’ sleep disturbances have been attributed to Parkinson’s disease symptoms, adverse medication effects, and neurodegeneration of central sleep regulatory areas. Altered circadian rhythms also may play a role. Supplemental exposure to bright light improves sleep quality and daytime vigilance in healthy older people and patients with dementia, but the treatment modality has not been studied systematically in patients with Parkinson’s disease, the researchers said.

One-Hour Treatment Intervals

To determine the safety and efficacy of light therapy on excessive daytime sleepiness associated with Parkinson’s disease, Dr. Videnovic and colleagues conducted a randomized, placebo-controlled trial.

They enrolled 31 patients with Parkinson’s disease and excessive daytime sleepiness (ie, an Epworth Sleepiness Scale score of 12 or greater). Patients were receiving stable dopaminergic therapy and did not have cognitive impairment or a primary sleep disorder. Investigators randomized participants 1:1 to receive bright light therapy (10,000 lux) or a control condition of dim-red light therapy (less than 300 lux). After a two-week baseline phase, participants received light therapy in one-hour intervals twice daily—in the morning (between 9 am and 11 am) and in the afternoon (between 5 pm and 7 pm)—for 14 days. The primary outcome measure was change in Epworth Sleepiness Scale score from baseline. During the study, each patient wore an actigraphy monitor and completed a daily sleep log and various other assessments.

During treatment, a light box was placed 86.4 cm away from the patient. Participants were instructed to sit quietly and not nap. They could listen to music or audiobooks.

The 31 patients (18 females) had an average age of about 63 (range, 32 to 77) and an average disease duration of about six years. Among patients who received bright light therapy, mean Epworth Sleepiness Scale score significantly improved from 15.81 at baseline to 11.19 post intervention. The improvement was significantly greater than that for patients in the control group, who had a mean Epworth Sleepiness Scale score of 15.47 at baseline and 13.67 post intervention.

Improvements in sleep quality, latency, and fragmentation were significantly greater in the bright light therapy group than in the control group. In both treatment arms, light therapy was associated with increased daily physical activity, as assessed by actigraphy, and reduced disease severity, as assessed by the Unified Parkinson’s Disease Rating Scale. Light therapy was not associated with significant changes in depression, anxiety, or quality of life.

In the active treatment group, one patient reported headache, and another patient reported sleepiness. One participant in the control group reported itchy eyes. The adverse events resolved spontaneously, and adherence to the study protocol was excellent, the researchers said.

Although improvement in the control arm may have been due to the placebo effect, it is also possible that “anchoring the light therapy to a strict twice-daily regimen provided means for structuring daily activities, which itself may be an interesting possible mechanism underlying the beneficial effects of … light therapy,” Dr. Videnovic and colleagues said. Future studies should address the optimal treatment parameters for light therapy in Parkinson’s disease, they added.

Whether light therapy produces direct alerting effects, influences the circadian system, or works through another mechanism is not clear. A limitation of the study was that light levels were not measured throughout the day, so patients in the control group could have received more light from other sources overall, compared with patients in the active treatment group, the investigators noted.

Chronobiologic Interventions

The study shows that chronobiologic interventions “can be used therapeutically in patients with Parkinson’s disease” and “introduce a new concept into the much-studied phenomenon of disturbed sleep and wakefulness in Parkinson’s disease,” said Birgit Högl, MD, of the Department of Neurology at the Medical University of Innsbruck in Austria, in an accompanying editorial. Although the study of chronobiology is complex, certain aspects of chronobiology can be “integrated into routine medical practice and improve outcomes for patients,” Dr. Högl said.

—Jake Remaly

Suggested Reading

Högl B. Circadian rhythms and chronotherapeutics-Underappreciated approach to improving sleep and wakefulness in Parkinson disease. JAMA Neurol. 2017;74(4):387-388.

Videnovic A, Klerman EB, Wang W, et al. Timed light therapy for sleep and daytime sleepiness associated with Parkinson disease: A randomized clinical trial. JAMA Neurol. 2017;74(4):411-418.

SAN DIEGO – A new study of medical records offers insights into the persistence of opioid use: Most patients who were prescribed opioid painkillers did not go back for a refill right away, but nearly half of patients who stopped taking the drugs for at least 6 months ended up using them again over a 3-year period.

“This key finding indicates that programs that address opioid use need to focus on long-term support and education to ensure that individuals do not become long-term users,” psychiatrist and lead author Shareh Ghani, MD, vice president and medical director of Magellan Health Services, San Francisco, said in an interview.

Researchers also found that opioid use appeared linked to three unexpected conditions – lipid disorders, hypertension, and sleep-wake disorders – and found that more than half of those who had at least two prescriptions for high-dose opioids kept taking the drugs over 18 months after an initial 90-day period.

SAN DIEGO – A new study of medical records offers insights into the persistence of opioid use: Most patients who were prescribed opioid painkillers did not go back for a refill right away, but nearly half of patients who stopped taking the drugs for at least 6 months ended up using them again over a 3-year period.

“This key finding indicates that programs that address opioid use need to focus on long-term support and education to ensure that individuals do not become long-term users,” psychiatrist and lead author Shareh Ghani, MD, vice president and medical director of Magellan Health Services, San Francisco, said in an interview.

Researchers also found that opioid use appeared linked to three unexpected conditions – lipid disorders, hypertension, and sleep-wake disorders – and found that more than half of those who had at least two prescriptions for high-dose opioids kept taking the drugs over 18 months after an initial 90-day period.

SAN DIEGO – A new study of medical records offers insights into the persistence of opioid use: Most patients who were prescribed opioid painkillers did not go back for a refill right away, but nearly half of patients who stopped taking the drugs for at least 6 months ended up using them again over a 3-year period.

“This key finding indicates that programs that address opioid use need to focus on long-term support and education to ensure that individuals do not become long-term users,” psychiatrist and lead author Shareh Ghani, MD, vice president and medical director of Magellan Health Services, San Francisco, said in an interview.

Researchers also found that opioid use appeared linked to three unexpected conditions – lipid disorders, hypertension, and sleep-wake disorders – and found that more than half of those who had at least two prescriptions for high-dose opioids kept taking the drugs over 18 months after an initial 90-day period.

Positive airway pressure, whether delivered continuously (CPAP) or as adaptive servoventilation, doesn’t reduce the rate of cardiovascular (CV) events or death in patients who have sleep apnea, according to a report published online July 11 in JAMA.

Positive airway pressure (PAP) relieves the symptoms of sleep apnea and has been reported to improve cardiovascular risk factors such as hypertension, insulin resistance, and endothelial dysfunction. However, whether the treatment improves “hard” vascular outcomes such as stroke and MI has never been established, said Jie Yu, MD, of the department of cardiology, Peking University and the Ministries of Health and Education, Beijing, and his associates.

They performed a systematic review of the literature and a meta-analysis of 10 randomized clinical trials that compared PAP against standard care or a sham treatment and had at least 6 months of follow-up for CV events. The meta-analysis involved 7,266 participants who had either obstructive (5,683 patients) or central (1,583 patients) sleep apnea. There were 356 major adverse CV events and 613 deaths during a median follow-up of 6-68 months.

The use of PAP showed no significant association with a range of outcomes: major adverse CV events (relative risk, 0.77; P = .19), major adverse CV events plus hospitalization for unstable angina (RR, 0.92; P = .54), cardiovascular death (RR, 1.15; P = .30), all-cause mortality (RR, 1.13; P = .08), noncardiovascular death (RR, 0.85; P = .33), acute coronary syndromes (RR, 1.00; P = .99), stroke (RR, 0.90; P = .47), and heart failure (RR, 1.03; P = .60). This lack of treatment benefit persisted regardless of length of follow-up, adherence to treatment, or baseline score on the apnea-hypopnea index, the investigators said (JAMA. 2017 July 11. doi: 10.1001/jama.2017.7967).

PAP also failed to improve blood pressure, body mass index, any lipid parameter, glycemia, or quality-of-life scores on the EQ-5D. It did improve sleepiness and some measures of physical and mental well-being.

“The evidence from these [randomized clinical trials] suggests that the association [between] sleep apnea and vascular outcomes and death ... may represent disease processes that cannot be ameliorated by PAP delivered at the average intensity achieved in these clinical trials or by currently feasible methods in clinical practice,” Dr. Yu and his associates said.

Their findings also “emphasize the importance of proven therapies, such as blood-pressure lowering, lipid lowering, and antiplatelet therapy, in patients with sleep apnea, who should be treated according to established guidelines for patients at elevated cardiovascular risk,” they added.

This study was supported by the National Health and Medical Research Council of Australia. Dr. Yu reported having no relevant financial disclosures. His associates reported ties to numerous industry sources.

Positive airway pressure, whether delivered continuously (CPAP) or as adaptive servoventilation, doesn’t reduce the rate of cardiovascular (CV) events or death in patients who have sleep apnea, according to a report published online July 11 in JAMA.

Positive airway pressure (PAP) relieves the symptoms of sleep apnea and has been reported to improve cardiovascular risk factors such as hypertension, insulin resistance, and endothelial dysfunction. However, whether the treatment improves “hard” vascular outcomes such as stroke and MI has never been established, said Jie Yu, MD, of the department of cardiology, Peking University and the Ministries of Health and Education, Beijing, and his associates.

They performed a systematic review of the literature and a meta-analysis of 10 randomized clinical trials that compared PAP against standard care or a sham treatment and had at least 6 months of follow-up for CV events. The meta-analysis involved 7,266 participants who had either obstructive (5,683 patients) or central (1,583 patients) sleep apnea. There were 356 major adverse CV events and 613 deaths during a median follow-up of 6-68 months.

The use of PAP showed no significant association with a range of outcomes: major adverse CV events (relative risk, 0.77; P = .19), major adverse CV events plus hospitalization for unstable angina (RR, 0.92; P = .54), cardiovascular death (RR, 1.15; P = .30), all-cause mortality (RR, 1.13; P = .08), noncardiovascular death (RR, 0.85; P = .33), acute coronary syndromes (RR, 1.00; P = .99), stroke (RR, 0.90; P = .47), and heart failure (RR, 1.03; P = .60). This lack of treatment benefit persisted regardless of length of follow-up, adherence to treatment, or baseline score on the apnea-hypopnea index, the investigators said (JAMA. 2017 July 11. doi: 10.1001/jama.2017.7967).

PAP also failed to improve blood pressure, body mass index, any lipid parameter, glycemia, or quality-of-life scores on the EQ-5D. It did improve sleepiness and some measures of physical and mental well-being.

“The evidence from these [randomized clinical trials] suggests that the association [between] sleep apnea and vascular outcomes and death ... may represent disease processes that cannot be ameliorated by PAP delivered at the average intensity achieved in these clinical trials or by currently feasible methods in clinical practice,” Dr. Yu and his associates said.

Their findings also “emphasize the importance of proven therapies, such as blood-pressure lowering, lipid lowering, and antiplatelet therapy, in patients with sleep apnea, who should be treated according to established guidelines for patients at elevated cardiovascular risk,” they added.

This study was supported by the National Health and Medical Research Council of Australia. Dr. Yu reported having no relevant financial disclosures. His associates reported ties to numerous industry sources.

Positive airway pressure, whether delivered continuously (CPAP) or as adaptive servoventilation, doesn’t reduce the rate of cardiovascular (CV) events or death in patients who have sleep apnea, according to a report published online July 11 in JAMA.

Positive airway pressure (PAP) relieves the symptoms of sleep apnea and has been reported to improve cardiovascular risk factors such as hypertension, insulin resistance, and endothelial dysfunction. However, whether the treatment improves “hard” vascular outcomes such as stroke and MI has never been established, said Jie Yu, MD, of the department of cardiology, Peking University and the Ministries of Health and Education, Beijing, and his associates.

They performed a systematic review of the literature and a meta-analysis of 10 randomized clinical trials that compared PAP against standard care or a sham treatment and had at least 6 months of follow-up for CV events. The meta-analysis involved 7,266 participants who had either obstructive (5,683 patients) or central (1,583 patients) sleep apnea. There were 356 major adverse CV events and 613 deaths during a median follow-up of 6-68 months.

The use of PAP showed no significant association with a range of outcomes: major adverse CV events (relative risk, 0.77; P = .19), major adverse CV events plus hospitalization for unstable angina (RR, 0.92; P = .54), cardiovascular death (RR, 1.15; P = .30), all-cause mortality (RR, 1.13; P = .08), noncardiovascular death (RR, 0.85; P = .33), acute coronary syndromes (RR, 1.00; P = .99), stroke (RR, 0.90; P = .47), and heart failure (RR, 1.03; P = .60). This lack of treatment benefit persisted regardless of length of follow-up, adherence to treatment, or baseline score on the apnea-hypopnea index, the investigators said (JAMA. 2017 July 11. doi: 10.1001/jama.2017.7967).

PAP also failed to improve blood pressure, body mass index, any lipid parameter, glycemia, or quality-of-life scores on the EQ-5D. It did improve sleepiness and some measures of physical and mental well-being.

“The evidence from these [randomized clinical trials] suggests that the association [between] sleep apnea and vascular outcomes and death ... may represent disease processes that cannot be ameliorated by PAP delivered at the average intensity achieved in these clinical trials or by currently feasible methods in clinical practice,” Dr. Yu and his associates said.

Their findings also “emphasize the importance of proven therapies, such as blood-pressure lowering, lipid lowering, and antiplatelet therapy, in patients with sleep apnea, who should be treated according to established guidelines for patients at elevated cardiovascular risk,” they added.

This study was supported by the National Health and Medical Research Council of Australia. Dr. Yu reported having no relevant financial disclosures. His associates reported ties to numerous industry sources.

Here are 6 articles in the July issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. High-dose Oral Vitamin D₃ Significantly Reduced Effects of Sunburn

To take the posttest, go to: http://bit.ly/2tmDiKc
Expires May 23, 2018

2. Women Less Likely to Be Diagnosed With Sleep Disorders

To take the posttest, go to: http://bit.ly/2rgLdne
Expires May 30, 2018

3. RA Treatment Delays Raise Risk for Long-term Disability

To take the posttest, go to: http://bit.ly/2tC0IGF
Expires May 30, 2018

4. Target Self-medication of Mood and Anxiety Symptoms

To take the posttest, go to: http://bit.ly/2vy5jel
Expires May 2, 2018

5. Two New Biomarkers for Breast Cancer Show Validity

To take the posttest, go to: http://bit.ly/2ve9H2L
Expires May 2, 2018

6. Time to Therapy for Gram-positive Bacteremia Reduced From 60 Hours to 4 Hours

To take the posttest, go to: http://bit.ly/2ssacIf​
Expires May 25, 2018

Here are 6 articles in the July issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. High-dose Oral Vitamin D₃ Significantly Reduced Effects of Sunburn

To take the posttest, go to: http://bit.ly/2tmDiKc
Expires May 23, 2018

2. Women Less Likely to Be Diagnosed With Sleep Disorders

To take the posttest, go to: http://bit.ly/2rgLdne
Expires May 30, 2018

3. RA Treatment Delays Raise Risk for Long-term Disability

To take the posttest, go to: http://bit.ly/2tC0IGF
Expires May 30, 2018

4. Target Self-medication of Mood and Anxiety Symptoms

To take the posttest, go to: http://bit.ly/2vy5jel
Expires May 2, 2018

5. Two New Biomarkers for Breast Cancer Show Validity

To take the posttest, go to: http://bit.ly/2ve9H2L
Expires May 2, 2018

6. Time to Therapy for Gram-positive Bacteremia Reduced From 60 Hours to 4 Hours

To take the posttest, go to: http://bit.ly/2ssacIf​
Expires May 25, 2018

Here are 6 articles in the July issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. High-dose Oral Vitamin D₃ Significantly Reduced Effects of Sunburn

To take the posttest, go to: http://bit.ly/2tmDiKc
Expires May 23, 2018

2. Women Less Likely to Be Diagnosed With Sleep Disorders

To take the posttest, go to: http://bit.ly/2rgLdne
Expires May 30, 2018

3. RA Treatment Delays Raise Risk for Long-term Disability

To take the posttest, go to: http://bit.ly/2tC0IGF
Expires May 30, 2018

4. Target Self-medication of Mood and Anxiety Symptoms

To take the posttest, go to: http://bit.ly/2vy5jel
Expires May 2, 2018

5. Two New Biomarkers for Breast Cancer Show Validity

To take the posttest, go to: http://bit.ly/2ve9H2L
Expires May 2, 2018

6. Time to Therapy for Gram-positive Bacteremia Reduced From 60 Hours to 4 Hours

To take the posttest, go to: http://bit.ly/2ssacIf​
Expires May 25, 2018

WASHINGTON – If patients have sleep disordered breathing with obstructive sleep apnea, will its treatment have cardiovascular disease benefits, especially in terms of the incidence or severity of atrial fibrillation?

Observational evidence suggests that apnea interventions may help these patients, but no clear case yet exists to prove that a breathing intervention works, experts say, and, as a result, U.S. practice is mixed when it comes to using treatment for obstructive sleep apnea (OSA), specifically continuous positive airway pressure (CPAP), to prevent or treat atrial fibrillation.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

This article was updated on 7/10/17.

WASHINGTON – If patients have sleep disordered breathing with obstructive sleep apnea, will its treatment have cardiovascular disease benefits, especially in terms of the incidence or severity of atrial fibrillation?

Observational evidence suggests that apnea interventions may help these patients, but no clear case yet exists to prove that a breathing intervention works, experts say, and, as a result, U.S. practice is mixed when it comes to using treatment for obstructive sleep apnea (OSA), specifically continuous positive airway pressure (CPAP), to prevent or treat atrial fibrillation.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

This article was updated on 7/10/17.

WASHINGTON – If patients have sleep disordered breathing with obstructive sleep apnea, will its treatment have cardiovascular disease benefits, especially in terms of the incidence or severity of atrial fibrillation?

Observational evidence suggests that apnea interventions may help these patients, but no clear case yet exists to prove that a breathing intervention works, experts say, and, as a result, U.S. practice is mixed when it comes to using treatment for obstructive sleep apnea (OSA), specifically continuous positive airway pressure (CPAP), to prevent or treat atrial fibrillation.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

This article was updated on 7/10/17.