Current Treatment Options in Neurology

, Volume 14, Issue 1, pp 36–49 | Cite as

Posttraumatic Headache in Military Personnel and Veterans of the Iraq and Afghanistan Conflicts

Headache (JR Couch, Section Editor)

Opinion statement

Headaches, particularly migraine, are common in US servicemembers (SMs) who are deployed to or have returned from theaters of combat operations in Iraq and Afghanistan. Concussions and exposure to explosive blasts may be a significant contributor to the increased prevalence of headaches in military veterans. Concussions, usually due to blast exposure, occur in approximately 20% of deployed SMs, and headaches are a common symptom after a deployment-related concussion. Posttraumatic headaches (PTHAs) in US SMs usually resemble migraines, and posttraumatic stress disorder (PTSD) and depression are common comorbidities. Treatment of PTHAs in SMs is based upon the treatment setting, whether the headaches are acute or chronic, the headache phenotype, and associated comorbidities. No randomized, controlled clinical trials evaluating the efficacy of therapies for PTHAs have been completed. Pharmacologic and nonpharmacologic management strategies should be selected on an individual basis. Acute therapy with NSAIDs or triptans and prophylactic therapy in acute and chronic settings using valproate, nortriptyline, amitriptyline, propranolol, topiramate, or botulinum toxin are discussed. Triptans and topiramate may be particularly effective in SMs with PTHA. Management of PTHA and other features of the posttraumatic syndrome should be multidisciplinary whenever possible.

Keywords

Headache disorders Military personnel Traumatic brain injury Concussion Treatment Management Assessment Headaches Migraine Posttraumatic headache NSAIDs Triptans Topiramate Prophylaxis 

Introduction

Headache is a common symptom following mild traumatic brain injury (TBI), herein referred to as concussion. The second edition of the International Classification of Headache Disorders (ICHD-2) classifies headache disorders as either primary or secondary [1]. Secondary headache syndromes are attributable to a specific inciting event, exposure, or condition, such as traumatic, infectious, neoplastic, inflammatory, systemic, or toxic processes. Posttraumatic headaches (PTHAs) are classified as secondary headache syndromes, as they follow trauma affecting the head, face, or neck. Head trauma may result in headaches associated with a variety of structural lesions that may have serious sequelae, but most patients with PTHAs attributable to concussions have no identifiable structural lesion.

PTHAs lack defining clinical features other than onset following a traumatic event. According to ICHD-2, acute PTHAs must begin within 7 days after head trauma or after regaining consciousness. Headaches that persist longer than 90 days from the initial trauma are classified as chronic PTHAs. Primary headache syndromes that worsen within 7 days of head trauma can also be classified as PTHAs [1]. These time criteria have been criticized for being arbitrary and based on consensus opinion [2, 3]. Although 80% of PTHAs have features of primary headache, headache characteristics are not a part of the current classification scheme [1, 4]. The different causes and severities of head trauma, the variability of PTHA phenotypes, and an incomplete understanding of the natural history and pathophysiology of PTHAs challenge any classification system.

Chronic PTHAs contribute to disability, lost productivity, health care costs, and decreased quality of life. A review of 1,670 patients from 12 studies revealed that chronic headaches occur in 58% of patients with TBI of any severity [5]. PTHAs occur frequently and are more likely to persist after concussion than after moderate or severe traumatic brain injury [6, 7]. The incidence of acute PTHA following a concussion ranges from 31% to 96% [8, 9, 10, 11]. PTHAs persist in 32%–78% of patients at 2–3 months, 8%–35% at 1 year, and 20% at 3–4 years [8, 9, 10, 11, 12].

Head trauma appears to be an important contributor to headache chronification. Couch et al. found that an attributable fraction of 15% of chronic daily headaches in a large case–control study could be attributed to a lifetime history of head or neck injury. This association was not limited to head trauma proximate to headache onset, and a dose–response relationship appeared to be present [13]. Speculation exists that persistence of PTHA is related to cultural factors such as increased litigation in Western societies [9], though direct evidence confirming this link is lacking. Medication overuse headache (MOH) is seen in 19%–42% of PTHA patients and may contribute to chronicity [2, 14]. Other risk factors for developing chronic PTHA include female gender, lower socioeconomic status, and prior history of headaches [7, 8, 10, 11, 15]. Psychiatric disorders are increased in patients with PTHA and contribute to headache chronicity, headache frequency, and headache-related disability [16, 17, 18, 19].

Primary headache disorders, particularly migraine, are common in US servicemembers (SMs) [20, 21]. During the first 6 years of the current conflicts in Iraq and Afghanistan (2001–2007), the incident rate of migraine increased yearly among US SMs, with the most marked increase noted in the US Army [22]. In a US Army combat brigade, 36% of soldiers reported headaches meeting criteria for migraine or possible migraine after a 1-year deployment to Iraq, a prevalence far exceeding that expected from the general US population [21]. When deployed, US SMs have increased exposure to physical and psychological factors that can predispose to headache disorders [23, 24, 25]. Concussions and exposure to explosive blasts may be significant contributors to the increased prevalence of headache disorders seen in deployed SMs. This review focuses on PTHAs in US troops that are currently or recently deployed and includes management strategies.

Posttraumatic headaches in US service members

Concussions occur in 15%–23% of US SMs deployed in support of combat operations in Iraq and Afghanistan [26, 27, 28]. From 1999 to 2009, 137,029 active component members of the Army, Navy, Air Force, Marine Corps, and Coast Guard met the Department of Defense (DOD) surveillance case definition for traumatic brain injury [29]. Explosive blast is the trauma mechanism in at least 80% of deployed SMs, whereas common mechanisms in the general population are motor vehicle accidents, falls, assaults, and sports [26, 27, 28]. Blast-induced neurotrauma has multiple potential mechanisms, including the primary effects from the blast wave, secondary effects caused by fragments or debris, tertiary effects of rapid acceleration and deceleration, and quaternary effects from flash burns and toxic fumes [30•, 31].

Headaches are a common feature of the acute posttraumatic syndrome in deployed US SMs. Terrio et al. found that 81.3% of soldiers from a US Army Brigade Combat Team with a deployment-related concussion reported headache immediately after the injury [28]. In the seminal study by Hoge et al., headache was the only symptom significantly associated with concussion in 2,525 infantry soldiers screened 3–4 months after returning from a 1-year deployment to Iraq, after controlling for posttraumatic stress disorder (PTSD) and depression [26]. Studies by Hoge and others, which used multi-symptom questionnaires, have found that 22%–40% of returning SMs with a history of a deployment-related concussion reported ongoing headaches [26, 27, 28]. In contrast, a study of a cohort of 978 returning soldiers with deployment-related concussion that used a headache-specific questionnaire found a 98% prevalence of headaches [32••].

Although headaches are common following concussion in returning US troops, not all of these headaches meet ICHD-2 criteria for PTHA. In a small series of 81 US Army soldiers from a single combat brigade who were referred to a military headache clinic for chronic headaches, 36% of soldiers with concussion had headaches meeting criteria for PTHA [25]. Similarly, in a study from the Madigan Traumatic Brain Injury Program, 37% of 978 soldiers with deployment-related concussion had headaches meeting ICHD-2 criteria for PTHA. An additional 19% of soldiers in this study had their headaches begin in the period from 1 to 4 weeks after a concussion [32••]. Many headaches in troops with a history of deployment-related concussion are actually primary headache disorders, most commonly migraine. A study using the military-wide electronic medical record found that the incidence of migraine after deployment was five times greater among SMs with a concussion during deployment [33•].

A large majority of PTHAs in SMs have a migraine phenotype. Migraine-like headaches occur in 60%–89% of US troops with PTHAs [25, 32••, 34]. In a neurology clinic–based series of 100 US Army soldiers with PTHA, 95% had headaches that otherwise would have met criteria for migraine had they not started immediately after head trauma [35]. In contrast, tension-type headache (TTHA) is usually reported as the most common headache phenotype for PTHAs in the general population, although there is significant variation from study to study, with percentages ranging from 6% to 85% [36]. A recent study in a civilian population suggests that migraine actually may be more common than previously recognized [37]. Combining multiple studies, Lew et al. found that 33.8% of PTHAs had characteristics of TTHA and 28.6% had migrainous features [36]. Why military PTHAs differ from civilian PTHAs with regard to headache characteristics has not been explained. The mechanism, particularly exposure to explosive blasts, may play a role in the onset of migraine headaches in deployed US troops. A combination of environmental, psychologic, traumatic, and genetic factors likely contributes to the onset of PTHAs with migrainous features in deployed US SMs.

Psychologic comorbidities frequently occur in SMs with a history of deployment-related concussion. In the study by Hoge et al., 33% of returning soldiers with deployment-related concussion met screening criteria for PTSD, and 13% screened positive for major depression [26]. Other studies have shown an even higher prevalence of psychologic comorbidities among soldiers with PTHA, with PTSD symptoms occurring in 45%–97% and depression symptoms occurring in 38% [35, 38]. Psychiatric disorders are important comorbid conditions in patients with chronic headache syndromes and should be identified and treated. PTSD is associated with chronic daily headache and may be a risk factor for headache chronification [39, 40]. Comorbid PTSD does not appear to exert a significant effect on the responsiveness of headaches to treatment [41]. Notwithstanding the significant debate surrounding the attribution of symptoms after a concussion to traumatic or psychiatric sequelae [42, 43], the importance of recognizing and treating comorbid psychiatric conditions in US SMs with PTHA cannot be understated.

Treatment

  • No randomized, controlled clinical trials evaluating the efficacy of therapies for PTHAs have yet been carried out. No treatments have been developed specifically for PTHA, nor has the US Food and Drug Administration (FDA) approved any medications for this indication. Treatment of PTHA is based on treatments for the primary headache disorder(s) most similar to the semiology of the patient’s headache (Class IV). The goals of treatment are no different than the goals in managing other headache disorders: (1) abort headache attacks, (2) decrease headache frequency, (3) reduce disability, and (4) prevent chronicity.

  • The evaluation and treatment of PTHAs differ somewhat in the acute and chronic settings. This is of particular importance when considering PTHAs in the US military. Acute PTHAs in US SMs are likely to occur in austere environments and clandestine circumstances. Subacute to chronic PTHAs are more likely to be managed at a fixed medical facility in theater or after the return from deployment. Patients with PTHA must also undergo evaluation and management of other symptoms of the posttrauma syndrome. A full discussion of all aspects of the multidisciplinary evaluation and management of concussion is outside the scope of this review. Guidelines for management of head trauma in the deployed and nondeployed settings are available from the Veterans Administration (VA), DOD, and Defense and Veterans Brain Injury Center (DVBIC) [44, 45, 46].

Acute posttraumatic headache

  • Initial assessment of acute PTHA begins with the history and physical examination. Moderate and severe traumatic brain injuries require urgent neuroimaging to rule out intracranial hemorrhage, skull fracture, or vascular injury. The presence of red flags such as alteration of consciousness, unusual behavior, neurologic deficits, seizures, or worsening headaches (or others listed fully elsewhere [45, 46]) in a patient with a concussion requires immediate evaluation and takes precedence over headache management. In theater, medical evacuation to a combat support hospital or higher level of care will be required if red flags, neurologic deficits, or suspicion of a moderate to severe TBI is present. The circumstances in which the acute PTHA occurs may influence the availability and feasibility of initial treatments. Triptan medications and several headache prophylactic medications are available in theater.

  • Table 1 is an algorithm for management of acute posttraumatic headache in the first 90 days after injury. (This is a proposed algorithm, and this approach has not been studied prospectively.) This algorithm specifically addresses headache management and does not include the treatment of other injuries or comorbidities. Treatment in the first 3 days focuses on rest and analgesic medications as needed. Management during days 4–14 begins to focus on aborting ongoing, recurrent headaches. Management from days 15–90 focuses on recognizing the headache type (e.g., migraine), with the goal of providing headache relief and preventing chronicity. Early use of prophylactic agents has not been studied in PTHA and has not been proven to prevent the development of chronic headaches. In our opinion, it is reasonable to initiate prophylactic medications in the first month in selected SMs with continuous or recurring headache syndromes of moderate to severe intensity, particularly if headache-related disability is significant.
    Table 1

    Treatment of deployment-related, acute posttraumatic headache

    0–72 h after concussion:

     Initial assessment:

     • History focused on headache red flags and neurologic examination. Refer to Defense and Veterans Brain Injury Center (DVBIC) guidelines [46] for evaluation of concussion in a deployed setting.

     • Neuroimaging if red flags or abnormal neurologic examination; consider medical evacuation.

     • Treat patient as follows if there are no red flags and/or secondary etiologies are excluded.

     Treatment:

     • Allow patient to rest in a quiet, dimly lit room.

     • Provide oral or IV hydration if needed.

     • Provide treatment for any minor physical injuries.

     • For headaches, initiate one of the following:

      ○ Acetaminophen 325–1000 mg up to four times per day. Do not exceed 4,000 mg in 1 day in healthy adults or 2,000 mg in elderly patients.

      ○ Ibuprofen 200–800 mg three times a day; do not exceed 2,400 mg per day.

      ○ Naproxen 250–500 mg twice a day; do not exceed 1,000 mg per day.

    Days 4–14 after concussion:

     Assessment:

     • Continue to encourage rest as needed and treat other injuries as appropriate.

     • Screen for and manage comorbidities, including acute stress disorder and sleep problems.

     • Treat patient as follows if there are no red flags and/or secondary etiologies are excluded.

     Treatment:

     • Continue acetaminophen, ibuprofen, or naproxen as above if effective. If not effective, consider treatment options below for abortive therapy.

     • Ketorolac 30 mg IV every 6–8 h; ensure no significant risk of systemic or intracranial bleeding.

     • Prochlorperazine or metoclopramide (oral or IV) or similar antiemetic, dosed every 6–8 h.

     • If refractory headache has migrainous features, consider the following:

      ○ Sumatriptan 50–100 mg orally (1 pill per day) or another triptan, for up to 5 days or until headache resolves

      ○ Prednisone 50–80 mg per day orally for 5–7 days; alternatively, use oral dexamethasone

     • If headache is refractory, consider occipital nerve blockade or trigger point injections in cervico-occipital region.

    Days 15–90 after concussion:

     Assessment:

     • Follow assessment steps as above, following DVBIC guidelines for evaluation of concussion in a subacute/chronic setting [44].

     Treatment:

     • Initiate trial of treatment as indicated for days 4–14, if not already done.

     • Initiate triptan medication for acute therapy if episodic headache has migrainous features.

     • If headache occurs 3 or more days per week or is particularly severe or prolonged, consider prophylactic medication, starting at lowest recommended dose and titrating gradually:

      ○ Topiramate, titrate to 50 mg twice daily

      ○ Amitriptyline, titrate to 50–75 mg daily

      ○ Propranolol, titrate to 80–120 mg total daily dose

      ○ Valproic acid, titrate to 1,000 mg daily

     • Consider 3–6 month trial of prophylaxis. If headache resolves, consider discontinuing medication, but restart if headaches recur.

     • Consider trial of botulinum toxin injections if oral prophylaxis is ineffective, not tolerated, or contraindicated.

     • Consider initiating trial of prazosin if patient with headaches has comorbid insomnia and/or nightmares. Titrate slowly (beginning with 1 mg nightly and increasing no more than 1 mg per week) up to 10 mg at night.

Chronic posttraumatic headache

  • The initial evaluation of chronic PTHAs in US troops may occur in varied settings, either during deployment, during post-deployment screening, or months after returning to the United States. The circumstances of individual SMs during deployment may have precluded headache evaluation and treatment other than the use of readily available over-the-counter analgesics, hydration, and rest. Because all returning SMs are screened for concussions, many soldiers with chronic PTHAs begin treatment within 3 months of returning home. In our experience, many soldiers have worsening of their headaches in the first weeks to months after returning from deployment.

  • It is imperative to recognize comorbidities such as cognitive impairment, sleep disorders, vestibular and balance disorders, psychosocial stressors, PTSD, depression, anxiety, alcohol or drug abuse, or concurrent physical injuries. As recommended by the VA and DOD, care of SMs with concussion should occur in a multidisciplinary setting where all symptoms and comorbidities can be addressed [44, Class IV].

Pharmacologic treatment

  • Figure 1 contains a treatment guideline for SMs with chronic PTHA. A detailed description of the headache should be obtained, including onset, location, quality, frequency, severity, duration, associated symptoms, triggers, functional impact, and changes in pattern over time. The specific characteristics of PTHAs have treatment implications, as shown in Figure 1. A patient may have more than one type of headache, so it is important to obtain a detailed description of each headache type. It also important to ask about headaches prior to the traumatic injury and whether there has been a marked change in the pattern of preexisting headaches. Similar to acute PTHA, the history and neurologic examination are used to identify any red flags or indications for neuroimaging. Careful documentation of the mechanism and circumstances related to the trauma may help guide further management of the PTHA and associated comorbidities. Headache disability scales such as the Headache Impact Test (HIT-6) [47] may help guide treatment over time, though they have not been validated in chronic PTHA.
    Figure 1

    Guidelines for management of chronic posttraumatic headache (HA). Adapted with permission from Erickson JC, Neely ET, Theeler BJ. Posttraumatic headache. Continuum Lifelong Learning Neurol 2010;16(6):55–78. Copyright ©2010, American Academy of Neurology. All rights reserved.

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) are a reasonable first option for abortive therapy of most types of PTHAs. Ibuprofen and naproxen are the most frequently used. Naproxen, with a longer half-life and a relative lack of association with MOH, may be the best choice. Because most PTHAs in US SMs have migrainous features, triptans should be strongly considered as first-line, abortive agents. In a retrospective series of US Army soldiers with PTHA, triptans were effective in 70% of cases, whereas NSAIDs were effective in 39% [35, Class IV]. The choice of triptan is based on patient preference, the preferred route (oral, nasal, or subcutaneous), and associated headache features such as nausea, which may preclude oral administration. Overall, triptans have an excellent safety record.

  • Antiemetics such as prochlorperazine, metoclopramide, or promethazine can be used as adjunctive therapies if significant nausea is present during the headache attack. If these dopamine-blocking agents are used regularly, extrapyramidal side effects may be of concern, requiring counseling and monitoring. We generally avoid combination analgesics and opioid or opioid-like medications whenever possible because of their association with MOH.

  • SMs with frequent, prolonged, or severe chronic PTHAs may benefit from headache prophylaxis. SMs with two or more moderate to severe headache attacks per week or 3 or more days of impaired activities per month over a period of several months despite the use of abortive medications are good candidates for headache prophylaxis. A practical therapeutic goal of a reduction of at least 50% in headache frequency should be set prior to initiation. Prophylactic medications require 4 weeks or longer to take effect, and the dose should be gradually increased. No prophylactic medication has been proven to be effective in chronic PTHA. Amitriptyline, valproate, and propranolol have shown some benefit in uncontrolled studies in civilians with PTHA [48, 49, 50, Class IV].

  • In a retrospective study of 100 US Army soldiers with PTHA, treatment with topiramate was associated with a significant reduction in headache frequency [35, Class IV]. The effectiveness of topiramate may have been due to the frequency of chronic daily headache, migraine features, and MOH. In contrast, amitriptyline was not associated with a reduction in headache frequency, possibly because of the low doses used by most patients (25–50 mg) [35, Class IV]. Notably, PTHAs triggered by an explosive blast were less responsive to treatment than PTHAs caused by a nonblast mechanism, suggesting that the mechanism of injury may have implications for treatment and prognosis. Valproate or propranolol are other options for treating PTHAs with migraine features, but their effectiveness has not been specifically studied in SMs. For prophylaxis of PTHAs with TTHA features, a low dose of amitriptyline or nortriptyline is recommended.

  • Choosing headache prophylactic medications that have secondary benefits for comorbid sleep, mood, or other pain disorders may be appropriate. However, treatment of each of the patient’s comorbidities (especially psychiatric comorbidities) should be rendered by an appropriate specialist. For example, initiating a low dose of a tricyclic antidepressant with the intention of adequately treating both PTHA and PTSD, while foregoing a mental health evaluation, is not recommended. An observational study in veterans with mild TBI found that sleep hygiene counseling and prazosin, an α-1 noradrenergic antagonist, were associated with improvements in both sleep and headaches [51, Class IV].

  • Occipital neuralgia and other neuralgiform pain disorders are commonly reported as important phenotypes of PTHA, although evidence from large studies is lacking. PTHAs with neuralgiform pain such as occipital or trigeminal neuralgia may benefit from treatment with an anticonvulsant such as carbamazepine, gabapentin, or lamotrigine. Occipital nerve blocks, consisting of injection of an anesthetic agent with or without corticosteroids, are used to treat a wide variety of headache syndromes [52]. A small case series of 10 patients with PTHA reported an 80% response rate with occipital nerve blockade [53, Class IV]. It is reasonable to initiate a trial of occipital nerve blockade in SMs whose head pain is reproduced with palpation over the greater or lesser occipital nerves. Occipital nerve blockade may also have utility as an abortive measure in SMs with PTHA with migraine or cervicogenic features.

  • Botulinum toxin injections may be considered for chronic PTHA, especially PTHAs resembling chronic migraine. Botulinum toxin is effective for chronic migraine and may have some benefit in patients with other chronic headache disorders [54, 55, 56]. By extrapolation, it may benefit some SMs with chronic PTHA syndromes after failure of prophylactic medications. Patient selection, dosing, and the technique of injecting botulinum toxin have not been systematically studied in PTHA.

Abortive agents

NSAIDs

NSAIDs, including ibuprofen, naproxen sodium, diclofenac, tolfenamic acid, and piroxicam, have Class IV evidence for benefit in acute headache disorders [57, Class IV]. These medications are reasonable first-line agents for abortive therapy for PTHAs. These agents inhibit cyclooxygenase (COX) 1 and 2 and inhibit prostaglandin synthesis. Ketorolac comes in intramuscular and intravenous formulations and may be beneficial to abort moderate to severe acute PTHAs. Combinations of NSAIDs and triptans may be considered in selected SMs with PTHA, and a combination agent containing sumatriptan and naproxen sodium is available.
Main side effects

The most common side effects of NSAIDs are gastrointestinal, including dyspepsia. Easy bleeding and bruising are uncommon side effects, although patients taking warfarin or other anticoagulants should probably avoid NSAIDs. Serious adverse events include esophagitis, gastrointestinal bleeding, renal failure, hepatic impairment, and increased risk of cardiovascular events.

Contraindications

The only absolute contraindication is hypersensitivity to NSAIDs, but NSAIDs should be used in caution in asthmatics and in patients with impaired cardiac, renal, or hepatic function.

Triptans

These agents bind to serotonin receptors on smooth muscle (5-HT1B) and trigeminal and dorsal root nerve terminals (5-HT1D) [58]. These drugs are FDA-approved for use as abortive agents for acute migraine attacks, but they have not been studied specifically in PTHAs. The ideal agent for use in SMs with PTHA depends on the desired formulation, drug interactions, half-life, and concurrent medications.

Available agents include sumatriptan, eletriptan, zolmitriptan, naratriptan, rizatriptan, frovatriptan, and almotriptan. All of these agents come in oral formulations. Sumatriptan has injectable formulations and also comes in a combination tablet with naproxen sodium. Sumatriptan and zolmitriptan have nasal formulations.
Contraindications

Triptans are contraindicated in the setting of ischemic cardiac, cerebrovascular, or peripheral vascular disease, uncontrolled hypertension, and hemiplegic or basilar-type migraines. Eletriptan is contraindicated in patients with arrhythmias or heart failure. Eletriptan and naratriptan are contraindicated in severe renal impairment. Naratriptan and almotriptan contain sulfonamide components and therefore should be used with caution in sulfa-allergic patients.

Main drug interactions

Triptans as a class should not be given within 24 h of ergot-type medications. The use of sumatriptan, zolmitriptan, or rizatriptan is contraindicated within 2 weeks of taking a monoamine oxidase inhibitor (MAOI). Eletriptan, frovatriptan, and almotriptan should be avoided in patients taking potent inhibitors of CYP3A4. The rizatriptan dose should be reduced to 5 mg in patients taking propranolol. There is a theoretical risk of serotonin syndrome if triptans are used by patients already taking selective serotonin or serotonin norepinephrine reuptake inhibitors, or with triptan monotherapy.

Main side effects

Sensations including tightness of the chest, jaw, or throat, limb heaviness, and fatigue are common and should not be construed as significant safety concerns.

Prophylactic agents

  • Whether an SM is a candidate for prophylaxis is based on the frequency and severity of the PTHA as well as the headache type (Fig. 1). Other agents that may be of benefit in PTHA but are not included in Figure 1 include gabapentin, zonisamide, and memantine.

  • Botulinum toxin injection may be a consideration for refractory cases of PTHA and for patients who cannot take or tolerate prophylactic medications.

Amitriptyline and nortriptyline

We use nortriptyline frequently in the place of amitriptyline in treating SMs with PTHA.
Standard dosage

Typical dosing is from 10 to 100 mg. The dose usually can be increased every 7–14 days in increments of 10–25 mg without significant side effects. Higher doses (up to 200 mg) may be considered for select patients still experiencing benefit with minimal adverse effects, but we do not routinely use doses above 100 mg.

Contraindications

These medications should not be given to patients with cardiac disease and should be used with caution in patients over the age of 60.

Main side effects

Drowsiness, dry mouth, constipation, and weight gain are common adverse effects. Serious effects include cardiac arrhythmias, lowered seizure threshold, and worsening of closed-angle glaucoma. Caution must be exercised when adding these to other serotonergic and noradrenergic medications because of a theoretical risk of serotonin syndrome.

Valproate

Standard dosage

We recommend starting at 250–500 mg per day. The dose can be increased in increments of 250–500 mg, to 750 mg twice a day. Higher doses can be used with careful monitoring. We typically do not exceed 1,500–2,000 mg per day.

Contraindications

This drug should not be used by women planning on getting pregnant or at risk of getting pregnant.

Main side effects

Side effects of valproate include tremor, hair loss, sedation, hepatic dysfunction, hyperammonemia, and weight gain. Ovarian dysfunction and polycystic ovary syndrome may be seen in younger women.

Special point

An intravenous formulation exists, which may be effective as an abortive therapy for prolonged or refractory PTHAs.

Propranolol

Standard dosage

The dosing of propranolol usually begins at 20 mg per day, with a gradual increase in dose by 20 mg every 5 days to a maximum total dose of 240 mg. Typical effective doses are 80–120 mg daily. After titration with a shorter-acting formulation, a long-acting formulation can be substituted.

Main side effects

Side effects include sedation, decreased energy, difficulty with digestion, hypotension, tachycardia, and worsening of depression.

Special point

Use with caution in SMs with comorbid depression.

Topiramate

Standard dosage

Start at 25 mg per day and advance by 25–50 mg per day every 5–7 days. The initial target maintenance dose is 100 mg daily, taken in two divided doses. If side effects are manageable and the SM is still experiencing benefit, the dose can be increased further, up to 200 mg per day if needed. Higher doses can be used in select cases.

Contraindications

Do not use in patients with a history of renal stones or acute glaucoma.

Main side effects

Side effects include sedation, anxiety, tremor, renal stones, numbness and tingling in the fingers and toes, and difficulty with finding words or thinking. Topiramate may be associated with hypohidrosis. Symptoms of acute glaucoma should prompt immediate ophthalmologic referral.

Other treatments

  • A number of nonpharmacologic measures, including behavioral and physical therapy, may be beneficial for SMs with chronic PTHA, particularly soldiers with other traumatic injuries, cognitive deficits, or psychiatric disorders, for whom they may serve an adjunctive role to pharmacologic management.

  • Uncontrolled studies have shown some benefit of cognitive behavioral therapy, biofeedback, and relaxation therapy in patients with PTHA [59, 60, Class IV]. In our experience, these therapies may benefit SMs with comorbidities including PTSD and insomnia.

  • Physical therapy, osteopathic manipulation, and acupuncture also may be beneficial and may be best used when a cervicogenic source of pain is suspected.

  • Counseling on lifestyle modification, identification of headache triggers, and headache education are other important parts of multidisciplinary management that should not be overlooked.

  • Another important component is screening and counseling for medication overuse, as 35% of soldiers with headaches after deployment-related concussions reported using a headache medication on 15 or more days per month, suggesting that MOH may contribute to chronicity in some soldiers with PTHA [32••].

Notes

Disclaimer

The views expressed are those of the authors and are not the official policies of the Department of the Army, the Department of Defense, or the US Government.

Disclosure

No potential conflicts of interest relevant to this article were reported.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders: 2nd edition. Cephalalgia. 2004;24 Suppl 1:9–160.Google Scholar
  2. 2.
    Haas DC. Chronic post-traumatic headaches classified and compared with natural headaches. Cephalalgia. 1996;16(7):486–93.PubMedCrossRefGoogle Scholar
  3. 3.
    Evans RW. Expert opinion: post-traumatic headaches among United States soldiers injured in Afghanistan and Iraq. Headache. 2008;48:1216–25.PubMedCrossRefGoogle Scholar
  4. 4.
    Couch JR, Lipton R, Stewart WF. Is post-traumatic headache classifiable and does it exist? Eur J Neurol. 2009;16:12–3.PubMedCrossRefGoogle Scholar
  5. 5.
    Nampiaparampil DE. Prevalence of chronic pain after traumatic brain injury: a systematic review. JAMA. 2008;300:711–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Yamaguchi M. Incidence of headache and severity of head injury. Headache. 1992;32(9):427–31.PubMedCrossRefGoogle Scholar
  7. 7.
    Couch JR, Bearss C. Chronic daily headache in the posttraumatic syndrome: relation to extent of head injury. Headache. 2001;41(6):559–64.PubMedCrossRefGoogle Scholar
  8. 8.
    Packard RC. Epidemiology and pathogenesis of posttraumatic headache. J Head Trauma Rehabil. 1999;14(1):9–21.PubMedCrossRefGoogle Scholar
  9. 9.
    Solomon S. Chronic post-traumatic neck and head pain. Headache. 2005;45(1):53–67.PubMedCrossRefGoogle Scholar
  10. 10.
    Faux S, Sheedy J. A prospective controlled study in the prevalence of posttraumatic headache following mild traumatic brain injury. Pain Med. 2008;9(8):1001–11.PubMedCrossRefGoogle Scholar
  11. 11.
    Stovner LJ, Schrader H, Mickeviciene D, et al. Headache after concussion. Eur J Neurol. 2009;16(1):112–20.PubMedCrossRefGoogle Scholar
  12. 12.
    Packard RC, Ham LP. Posttraumatic headache: determining chronicity. Headache. 1993;33(3):133–4.PubMedCrossRefGoogle Scholar
  13. 13.
    Couch JR, Lipton RB, Stewart WF, Scher AI. Head or neck injury increases the risk of chronic daily headache: a population-based study. Neurology. 2007;69:1169–77.PubMedCrossRefGoogle Scholar
  14. 14.
    Baandrup L, Jensen R. Chronic post-traumatic headache: a clinical analysis in relation to the International Headache Classification 2nd edition. Cephalalgia. 2005;25(2):132–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Jensen OK, Nielsen FF. The influence of sex and pre-traumatic headache on the incidence and severity of headache after head injury. Cephalalgia. 1990;10(6):285–93.PubMedCrossRefGoogle Scholar
  16. 16.
    Duckro PN, Chibnall JT, Tomazic TJ. Anger, depression, and disability: a path analysis of relationships in a sample of chronic posttraumatic headache patients. Headache. 1995;35(1):7–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Branca B. Neuropsychologic aspects of post-traumatic headache and chronic daily headache. Curr Pain Headache Rep. 2006;10(1):54–66.PubMedCrossRefGoogle Scholar
  18. 18.
    TTatrow K, Blanchard EB, Hickling EJ, Silverman DJ. Posttraumatic headache: biopsychosocial comparisons with multiple control groups. Headache. 2003;43(7):755–66.PubMedCrossRefGoogle Scholar
  19. 19.
    Gfeller JD, Chibnall JT, Duckro PN. Postconcussion symptoms and cognitive functioning in posttraumatic headache patients. Headache. 1994;34(9):503–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Helseth EK, Erickson JC. The prevalence and impact of migraine on US military officer trainees. Headache. 2008;48:883–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Theeler BJ, Mercer R, Erickson JC. Prevalence and impact of migraine among U.S. Army soldiers deployed in support of Operation Iraqi Freedom. Headache. 2008;48:876–82.PubMedCrossRefGoogle Scholar
  22. 22.
    Migraines and other headaches, active components, U.S. Armed Forces, 2001–2007. MSMR Med Surveill Mon Rep. 2008;15(4):6–10.Google Scholar
  23. 23.
    Theeler BJ, Kenney K, Prokhorenko OA, Fideli US, Campbell W, Erickson JC. Headache triggers in the US Military. Headache. 2010;50:790–4.PubMedCrossRefGoogle Scholar
  24. 24.
    Afari N, Harder LH, Madra NJ, et al. PTSD, combat injury, and headache in veterans returning from Iraq/Afghanistan. Headache. 2009;49:1267–76.PubMedCrossRefGoogle Scholar
  25. 25.
    Theeler BJ, Erickson JC. Mild head trauma and chronic headaches in returning US soldiers. Headache. 2009;49:529–34.PubMedCrossRefGoogle Scholar
  26. 26.
    Hoge CW, McGurk D, Thomas JL, Cox AL, Engel CC, Castro CA. Mild traumatic brain injury in U.S. soldier returning from Iraq. N Engl J Med. 2008;358:453–63.PubMedCrossRefGoogle Scholar
  27. 27.
    Schwab KA, Ivins B, Cramer G, et al. Screening for traumatic brain injury in troops returning from deployment in Afghanistan and Iraq: Initial investigation of the usefulness of a short screening tool for traumatic brain injury. J Head Trauma Rehabil. 2007;22:377–89.PubMedCrossRefGoogle Scholar
  28. 28.
    Terrio H, Brenner LA, Ivins BJ, Cho JM, Helmick K, Schwab K, Scally K, Bretthauer R, Warden D. Traumatic brain injury screening: preliminary findings in a US Army Brigade Combat Team. J Head Trauma Rehabil. 2009;24(1):14–23.PubMedCrossRefGoogle Scholar
  29. 29.
    Deriving case counts from medical encounter data: considerations when interpreting health surveillance reports. MSMR Med Surveill Mon Rep. 2009;16(12):2–8.Google Scholar
  30. 30.•
    Cernak I. The importance of systemic response in the pathobiology of blast-induced neurotrauma. Front Neurol. 2010;1:151.PubMedGoogle Scholar
  31. 31.
    Ling G, Bandak F, Armonda R, Grant G, Ecklund J. Explosive blast neurotrauma. J Neurotrauma. 2009;26(6):815–25.PubMedCrossRefGoogle Scholar
  32. 32.••
    Theeler BJ, Flynn FG, Erickson JC. Headaches after concussion in US soldiers returning from Iraq or Afghanistan. Headache. 2010;50(8):1262–72.PubMedCrossRefGoogle Scholar
  33. 33.•
    Risk factors for migraine after OEF/OIF deployment, active component, U.S. Armed Forces. MSMR Med Surveill Mon Rep. 2009;16(12):10–13. This study used the military-wide electronic medical record to determine risk factors associated with migraine after return from deployment to Iraq or Afghanistan.Google Scholar
  34. 34.
    Ruff RL, Ruff SS, Wang XF. Headaches among Operation Iraqi Freedom/Operation Enduring Freedom veterans with mild traumatic brain injury associated with exposures to explosions. J Rehabil Res Dev. 2008;45:941–52.PubMedCrossRefGoogle Scholar
  35. 35.
    Erickson JC. Treatment outcomes of chronic post-traumatic headaches after mild head trauma in US soldiers: an observational study. Headache. 2011;51(6):932–44.PubMedCrossRefGoogle Scholar
  36. 36.
    Lew HL, Lin PH, Fuh JL, Wang SJ, Clark DJ, Walker WC. Characteristics and treatment of headache after traumatic brain injury: a focused review. Am J Phys Med Rehabil. 2006;85:619–27.PubMedCrossRefGoogle Scholar
  37. 37.
    Lucas S, Hoffman JM, Bell K, Dikmen S. Natural history of headache in the first year after traumatic brain injury. Neurology. 2011; 76(9) supplement 4:A161.Google Scholar
  38. 38.
    Kozminski M. Combat-related posttraumatic headache: diagnosis, mechanisms of injury, and challenges to treatment. J Am Osteopath Assoc. 2010;110(9):514–9.PubMedGoogle Scholar
  39. 39.
    Peterlin BL, Tietjen G, Meng S, Lidicker J, Bigal M. Post-traumatic stress disorder in episodic and chronic migraine. Headache. 2008;48(4):517–22.PubMedCrossRefGoogle Scholar
  40. 40.
    de Leeuw R, Schmidt JE, Carlson CR. Traumatic stressors and post-traumatic stress disorder symptoms in headache patients. Headache. 2005;45(10):1365–74.PubMedCrossRefGoogle Scholar
  41. 41.
    Rosenthal J, Erickson JC. Post-traumatic stress disorder in US soldiers with migraine and post-traumatic headache. Headache. 2011;51(S1):3–4.Google Scholar
  42. 42.
    Hoge CW, Goldberg HM, Castro CA. Care of war veterans with mild traumatic brain injury–flawed perspectives. N Engl J Med. 2009;360(16):1588–91.PubMedCrossRefGoogle Scholar
  43. 43.
    Ruff RL, Riechers RG, Ruff SS. Relationships between mild traumatic brain injury sustained in combat and post-traumatic stress disorder. F1000 Med Rep. 2010;2:64.PubMedGoogle Scholar
  44. 44.
    VA/DoD Evidence Based Guideline: Evaluation and Management of Concussion/mTBI - Subacute/Chronic (CONUS). http://www.dvbic.org/. Accessed November 2011.
  45. 45.
    Clinical Guidance for Evaluation and Management of Concussion/mTBI - Acute/Subacute (CONUS). http://www.dvbic.org/. Accessed November 2011.
  46. 46.
    Clinical Guidance for Evaluation and Management of Concussion/mTBI - Acute/Subacute. Deployed Setting Version. http://www.dvbic.org/.
  47. 47.
    Kosinski M, Bayliss MS, Bjorner JB, et al. A six-item short-form survey for measuring headache impact: the HIT-6. Qual Life Res. 2003;12(8):963–74.PubMedCrossRefGoogle Scholar
  48. 48.
    Packard RC. Treatment of chronic daily posttraumatic headache with divalproex sodium. Headache. 2000;40(9):736–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Weiss HD, Stern BJ, Goldberg J. Post-traumatic migraine: chronic migraine precipitated by minor head or neck trauma. Headache. 1991;31(7):451–6.PubMedCrossRefGoogle Scholar
  50. 50.
    Tyler GS, McNeely HE, Dick ML. Treatment of post traumatic headache with amitriptyline. Headache. 1980;20(4):213–6.PubMedCrossRefGoogle Scholar
  51. 51.
    Ruff RL, Ruff SS, Wang XF. Improving sleep: initial headache treatment in OIF/OEF veterans with blast-induced mild traumatic brain injury. J Rehabil Res Dev. 2009;46:1071–84.PubMedCrossRefGoogle Scholar
  52. 52.
    Tobin J, Flitman S. Occipital nerve blocks: when and what to inject? Headache. 2009;49(10):1521–33.PubMedCrossRefGoogle Scholar
  53. 53.
    Hecht JS. Occipital nerve blocks in postconcussive headaches: a retrospective review and report of ten patients. J Head Trauma Rehabil. 2004;19(1):58–71.PubMedCrossRefGoogle Scholar
  54. 54.
    Freitag FG, Diamond S, Diamond M, Urban G. Botulinum toxin type A in the treatment of chronic migraine without medication overuse. Headache. 2008;48(2):201–9.PubMedGoogle Scholar
  55. 55.
    Mathew N, Kailasam J, Meadors L. Predictors of response to botulinum toxin type A (BoNTA) in chronic daily headache. Headache. 2007;48(2):194–200.PubMedGoogle Scholar
  56. 56.
    Matthew NT, Jaffri SF. A double-blind comparison of onabotulinum toxin A (BOTOX) and topiramate (TOPAMAX) for the prophylactic treatment of chronic migraine. Headache. 2009;49(10):1466–78.CrossRefGoogle Scholar
  57. 57.
    Whyte C, Tepper SJ, Evans RW. Expert Opinion: Rescue me: rescue medication for migraine. Headache. 2010;50:307–13.PubMedCrossRefGoogle Scholar
  58. 58.
    Levy D, Jakubowski M, Burstein R. Disruption of communication between peripheral and central trigeminovascular neurons mediates the antimigraine action of 5HT 1B/1D receptor agonists. Proc Natl Acad Sci U S A. 2004;101:4274–9.PubMedCrossRefGoogle Scholar
  59. 59.
    Gurr B, Coetzer BR. The effectiveness of cognitive-behavioral therapy for post-traumatic headaches. Brain Inj. 2005;19(7):481–91.PubMedCrossRefGoogle Scholar
  60. 60.
    Tatrow K, Blanchard EB, Silverman DJ. Post-traumatic headache: an exploratory treatment study. Appl Psychophysiol Biofeedback. 2003;28(4):2670–8.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Medical Corps, United States ArmyFort Sam HoustonUSA
  2. 2.187th Medical Battalion, AMEDD Student DetachmentFort Sam HoustonUSA
  3. 3.Department of Medicine, Neurology ServiceMadigan Army Medical CenterFort LewisUSA

Personalised recommendations