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capable of causing drug dependence; therefore we have prescribed it sparingly Numerous other agents have proved to be effective and each has had a period of popularity among neurologists (the review by Schulman and Silberstein is recomended) Overall, for severe attacks, sumatriptan or one of the newer triptans (eg, zolmitriptan, rizatriptan, etc) and the ergot alkaloids, ergotamine tartrate, and particularly dihydroergotamine (DHE), are probably the most effective forms of treatment and are best administered early in the attack A single 6-mg dose of sumatriptan or its equivalent [selective agonists of serotonin (5HT) receptors], given subcutaneously, is an effective and well-tolerated treatment for migraine attacks An advantage of sumatriptan, and now of some others in this class, is the ease of self-administration using prepackaged injection kits, thus avoiding frequent and inconvenient visits to the emergency department Sumatriptan can also be given orally in a 50- or 100-mg tablet, zolmitriptan in a 25- or 5-mg tablet, and rizatriptan in a 10mg dose repeated, if needed, in 2 h (and other similar drugs in this class), but their latencies for headache relief are longer than that of the subcutaneous injection A tabulated comparison of the triptan drugs is given in the review by Goadsby and colleagues; others in this class are sure to be developed and subtle differences between them undoubtedly will be touted, but these are usually negligible in practical terms Sumatriptan is available as a nasal spray, which is particularly useful in patients with nausea and vomiting The response rate after 2 h is similar to that of the orally administered drug, and the nasal spray acts more rapidly Ergotamine is an equally effective agent, but some safety issues and aggressive marketing of the triptans have reduced its use This is an alpha-adrenergic agonist with strong 5HT receptor af nity and vasoconstrictive action The drug is taken as an uncoated 1- to 2-mg tablet of ergotamine tartrate, held under the tongue until dissolved (or swallowed), and repeated every half hour until the headache is relieved or until a total of 8 mg is taken A single oral dose of promethazine (Phenergan) 50 mg, or of metoclopramide (Reglan) 20 mg, given with the ergotamine, relaxes the patient and allays nausea and vomiting Patients in whom vomiting prevents oral administration may be given ergotamine by rectal suppository or DHE by nasal spray or inhaler (one puff at onset and another at 30 min) or can learn to give themselves a subcutaneous injection of DHE (usual dosage, 1 mg) Caffeine, 100 mg, is thought, on slim evidence, to potentiate the effects of ergotamine and other medications for migraine When ergotamine is administered early in the attack, the headache will be abolished or reduced in severity and duration in some 70 to 75 percent of patients For severely ill patients who arrive in the emergency department or physician s of ce, having failed to obtain relief with the usual medications, Raskin has found metoclopramide 10 mg IV, followed by DHE 05 to 1 mg IV every 8 h for 2 days, to be effective We also use this approach in cases of status migrainosus Intravenous and oral corticosteroids have also been useful in some refractory cases and as a means of terminating migraine status, but they should not be given continuously The potential success of metoclopropamide should not be dismissed, as we and others have occasionally found that the headache abates after this initial injection The sympathomimetic drug isometheptene combined with a sedative and acetaminophen (Midrin) has been useful for some patients and probably acts in a similar way to ergotamine and sumatriptan A wide array of other drugs has been recommended as adjunctive therapy, eg, metoclopramide, prochlorperazine, chlorpromazine, ketorolac, and intranasal lidocaine Even anticonvul-.

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This has been phrased with an inductive argument in mind We have already discussed both the base case and the inductive step Can you ll in the details The overall running time of this algorithm is linear, O(|V | + |E|), for exactly the same reasons as depth- rst search Each vertex is put on the queue exactly once, when it is rst encountered, so there are 2 |V | queue operations The rest of the work is done in the algorithm s innermost loop Over the course of execution, this loop looks at each edge once (in directed graphs) or twice (in undirected graphs), and therefore takes O(|E|) time Now that we have both BFS and DFS before us: how do their exploration styles compare Depth- rst search makes deep incursions into a graph, retreating only when it runs out of new nodes to visit This strategy gives it the wonderful, subtle, and extremely useful properties we saw in the 3 But it also means that DFS can end up taking a long and convoluted route to a vertex that is actually very close by, as in Figure 41 Breadth- rst search makes sure to visit vertices in increasing order of their distance from the starting point This is a broader, shallower search, rather like the propagation of a wave upon water And it is achieved using almost exactly the same code as DFS but with a queue in place of a stack 107

sants may have a role if the headache persists for days Each of these drugs, given alone, is effective in alleviating the headache in about half of these patients This fact emphasizes the need for blinded placebo trials for any new drug that is introduced for the treatment of headache Because of the danger of prolonged arterial spasm in patients who have vascular (particularly coronary) disease or are pregnant, the use of ergotamine is not advised Similarly, triptan medications should not be given to patients with uncontrolled hypertension or to those taking serotonergic and tricyclic antidepressants Elderly patients should have electrocardiographic and blood pressure monitoring during and after administration of the drugs Even in healthy individuals, more than 10 to 15 mg of ergotamine or 6 mg of DHE per week is not advised Both worsening of angina and transmyocardial infarction have occurred From time to time, cases of severe but reversible cerebral vasospasm are reported after the use of ergotamine (as they are occasionally after use of the triptan drugs) Sudden worsening of the headache and uctuating signs of focal cerebral ischemia have occurred in the cases with which we are familiar Diffuse cerebral vasoconstriction underlies many of these cases Of particular danger is the often unnoticed, concurrent use of other sympathomimetic drugs such as phenylpropanolamine as in one of the cases described by Singhal and colleagues and by Meschia et al (see discussion of Call-Fleming syndrome, Diffuse Vasoconstriction, page 730) Cerebral hemorrhage is another rare complication that relates possibly to hypertension induced by ergots or triptans If, in an individual attack, all of the foregoing measures fail, it is probably best to resort brie y to narcotics, which usually give the patient a restful, pain-free sleep Halfway measures at this point are usually futile However, the use of narcotics as the mainstay of acute or prophylactic therapy is to be avoided Most recently, based on the action of certain peptides in the trigeminovascular complex, novel antagonists of calcitonin generelated peptide (CGRP) have been used with therapeutic success (Olesen et al) Drugs of this type work by a different mechanism than do the triptans and may be alternatives in the future Prophylactic Treatment In individuals with frequent migrainous attacks, efforts at prevention are worthwhile The most effective agents have been beta blockers, certain anticonvulsants, and antidepressants Considerable success has been obtained with propranolol (Inderal), beginning with 20 mg three times daily and increasing the dosage gradually to as much as 240 mg daily, probably best given as a long-acting preparation in the higher dosage ranges Underdosing is a major reason for ineffectiveness If propranolol is unsuccessful, one of the other beta blockers, speci cally one that does not have agonist properties atenolol (40 to 160 mg/day), timolol (20 to 40 mg/day), or metoprolol (100 to 200 mg/day) may prove to be effective In patients who do not respond to these drugs over a period of 4 to 6 weeks, valproic acid 250 mg taken three to four times daily or one of the tricyclic antidepressants (eg, amitriptyline, 75 to 125 mg nightly) may be tried; it is not clear if the newer antidepressants are as effective Calcium channel blockers (eg, verapamil, 320 to 480 mg/day; nifedipine, 90 to 360 mg/ day) are also reportedly effective in decreasing the frequency and severity of migraine attacks in some patients, but there is typically a lag of several weeks before bene t is attained and our success with them has been limited Methysergide (Sansert), an ergot-like preparation that was more widely used in the past, in doses of 2 to 6 mg daily for several weeks or months is effective in the prevention of migraine Retroperitoneal and pulmonary brosis are rare.

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