Preemptive Therapy for Acute Migraine Headache: Treatment during the “prodrome”
As was discussed in a previous issue, a compleat migraine episode, one that produces all the courses from soup to nuts, includes 4 phases: a prodrome, aura, headache phase and a postdrome.
Not all migraineurs are “blessed” with this complete meal. Only about 25% will ever experience aura symptoms, and very few of those 25% will have aura with each and every migraine episode. In an individual migraineur, episodes may vary such that only a portion of the various phases are experienced in a given episode. For example, aura can occur independent of any temporally associated headache but may be followed by a postdrome. The migraineur may experience his or her typical prodromal symptoms even in the absence of aura or postdrome and with little or no headache. For those of us who have migraine – and especially for those with chronic migraine - these “prodromal days” are days when we describe ourselves as “feeling migrainous”. Even absent much in the way of headache, one is out of sorts, cognitively a bit foggy, fatigued or afflicted with one of other many vague but unpleasant prodromal symptoms.
In other words, any permutation of the 4 phases may occur, and to complicate matters further the phases may not necessarily occur neatly, one after the other in the order described (eg, aura may persist into and even beyond the headache phase). As we have emphasized many times in this magazine, migraine is the “Baskin Robbins” of headache; migraine episodes come in many different flavors, and it is much more common for migraine episodes to be symptomatically diverse than to be stereotyped.
In our clinic we often advise patients that acute migraine headache is a symptom best treated early, as it is first developing. For that 25% of migraineurs who at times have aura, if their aura symptoms invariably are followed by headache of moderate to severe intensity we will recommend trying certain medications during the aura phase, before the headache develops. What about treating even earlier? Say, during the prodromal phase?
Whereas only 25% of migraineurs ever experience aura, over 2/3rds of migraineurs report having symptoms typical of prodrome prior to the headache phase. Those symptoms are legion, and their diversity ranges from something as specific as repetitive yawning, heightened sensitivity to light or urinary frequency to “I can’t explain it precisely, but I just know I’m going to get a headache.” What causes these prodromal symptoms? From where in the nervous system do they arise? And, as many migraineurs find the prodrome to be as distressing as the headache that follows, how can we treat prodrome?
All good questions and, at this point no good answers. Many believe that prodromal and postdromal symptoms may arise from the hypothalamus, a small chunk of gray matter within the brain that serves as the chronobiologic clock of the body, regulating everything from body temperature to sex drive. Hard to prove. Not surprisingly, without a clear understanding of prodrome’s biologic circuitry we lack any evidence-based therapy for treating the prodromal symptoms.
In PRODROME, an interesting study recently conducted, migraineurs who consistently experienced prodromal symptoms followed by headache were randomized to taking either ubrogepant (Ubrelvy) or placebo during the prodromal phase. Those research subjects who took Ubrelvy were significantly less likely to experience a moderate to severe headache immediately subsequent to their prodromes. Although the medication was administered before any migraine headache had developed, it lingered long enough in the brain to short-circuit the electrochemical pathway that otherwise would have generated a headache.
While the results of this study do not provide any support for Ubrelvy as a treatment for the prodrome itself, it does reinforce the long-held notion that treatment administered early in the course of a migraine episode is more likely to be effective for preventing or reducing headache than treatment administered at a later point. Two aspirin and a cup of coffee taken early can be far more effective than an intravenous narcotic administered late.