Traumatic Brain Injury: Treatment of Post-traumatic Headaches
Increased attention to traumatic brain injury (TBI) has raised renewed interest in one of its consequences—post-traumatic headaches (PTH). Most often these have the characteristics of migraines, migrainous headaches, and mixed tension-type headaches (TTH) and migraines, as was discussed in Part 1 of this series.1 There have been a number of recent articles in medical journals that have renewed the debate about TBI, including an article by Robbins and Conidi on sports-related injuries. According to Seifert, there are approximately 3.8 million sports-related concussions occurring each year, providing unique treatment challenges for medical personnel.3 The presence of new onset or persistent headache following an injury often complicates return-to-play decisions.
The second part of this series specifically addresses the treatment of PTH and does not claim to be comprehensive. It consists of three parts: Acute treatment of post-TBI headaches using migraine-specific therapy, prophylactic therapy to suppress post-TBI headaches, and interventional treatments used in our outpatient headache clinic. Part 3 of the series will discuss evaluation, treatment, and rehabilitation.
Quite frankly, the "classic" migraine-specific abortive medications used for treatment of acute migraines and migrainous headaches—for example, dihydroergotamine (DHE-45) and triptans—are FDA indicated for moderate to severe migraines. A reformulated diclofenac potassium preparation (Cambia), with very rapid absorption kinetics, is also FDA indicated for mild to moderate migraine. The spectrum of abortive medications is covered extremely well in some of the comprehensive textbooks about headaches and migraines, including the role of opioids.4-6 A selective list of FDA-approved agents are highlighted in Table 1.
Migraine-specific abortive therapy centers on the triptan family of compounds. Theses agents primarily decrease neural activity in trigeminovascular afferent nerves that are sending signals from dural nerve endings to the trigeminal nucleus caudalis in the brainstem. They also have vasoconstrictive properties on blood vessels in this system, but the main effect is on neural firing. Triptans act specifically on serotonin (5HT)-1B and 1D receptors. They should be used for disabling migraines that are moderate to severe in intensity. If migraines are present >2 to 3 times per week, it may be wise to consider a suppressive or prophylactic medication (see next section).
Triptans can be used in conjunction with antiemetics (metoclopramide [Reglan], ondansetron [Zofran], promethazine [Phenergan], etc), and perhaps anti-inflammatory compounds. They are indicated for moderate to severe migraines, but early intervention in the migraine process is always desirable. Some of the triptans are available in faster delivery systems like injectable and nasal spray.
Nausea should always be treated alongside the migraine. Our preference is for the prescription of the more potent antiemetics, including ondansetron or metoclopramide. In the author's practice, we successfully have used these, as well as droperidol intravenously (IV) in the clinic (in small doses).
When TBI migraines become disabling to one's lifestyle and occur more frequently than 3 times per week despite successful treatment with triptans or other migraine-specific therapies, it may be time to think about suppressive or prophylactic therapy. Only four medications are FDA approved for this indication: topiramate (Topamax), valproate sodium, propranolol, and timolol (the last of which is available as an optic solution primarily, and is very hard to find in tablet form). In addition, Botox is currently the only medication approved for prophylactic treatment of chronic migraine (Table 2).
The first two medications were originally approved as anticonvulsants, but were found to be effective in managing migraine, chronic daily headaches, and cluster headaches. Sedation and cognitive side effects, such as confusion or memory problems, however, may limit the use of topiramate. Valproate sodium has been a popular migraine preventive. The agent is usually well tolerated in the lower doses used for headaches; however, the FDA recently issued a warning that valproate sodium can cause decreased IQ scores in children whose mothers took the medication during pregnancy. The agency now reports that these agents are contraindicated in pregnant women for the prevention of migraine headaches.7 The β-blocker propranolol is often tried as initial prophylaxis therapy. Originally, it was noted serendipitously to help migraine headaches when it was being used for management of blood pressure and cardiac rhythm disorders.
When we think of preventative therapy, it is wise to think about co-morbid post-concussion symptoms. This might include anxiety, depression, bipolar-like symptoms, seizures, high blood pressure, irritability, poor sleep, and mood swings. Besides these FDA-approved medications, virtually all of the anticonvulsants (we much prefer the phrase "neuronal stabilizing agents") have been tried in small trials, which are usually open label in nature. For example, the author published the first data on migraine and neuropathic pain management treated with oxcarbazepine, levetiracetam, and zonisamide8-10 soon after they were officially released as seizure medications. Other agents in this large group were also studied for migraines, chronic daily headaches, and neuropathic pain by the same author.11 Unfortunately, in the vast majority of these studies the industry chose not to study the medication formally in a double-blind, placebo-controlled fashion.
Similarly, many agents that are approved for other uses have been used off-label for their abilities to help migraine patterns. Post-TBI migraines, when accompanied by cognitive difficulties, have been shown to respond to the treatment memantine (Namenda), officially on the market only for management of dementia.12,13 However, many studies, primarily from Europe, have used this agent for various pain conditions off label, and we have used it as an agent to help with cognition after TBI.14
Antidepressants, particularly the serotonin-norepinephrine reuptake inhibitors, can help depression and anxiety, but they can also reduce pain and migraines post-TBI. The author has used venlafaxine (Effexor), duloxetine (Cymbalta), and milnacipran (Savella) off-label in his clinical practice. Medication in other categories (so-called antipsychotic agents) have also been used to suppress migraines (eg, ziprasidone) and can be very useful in post-concussion headaches accompanied by irritability, mood instability, and sleep disorders.15