Triptans are all different.

T HERE ARE 4 triptans currently available in theUnitedStates, and 3moreareexpectedto be approved by the Food and Drug Administration. Althoughtheyareall5-HT1B/1D (serotonin1B/1D) agonists, they each have slightly different pharmacokinetic characteristics and clinical strengths andweaknesses,andtheycanbeused in special ways to optimize migraine therapy. Thus, triptans differ significantly clinically, and the astute clinicianusesthesedifferencestooptimize patient treatment. Sumatriptan (Imitrex) was the first triptan synthesized. It offers flexibility of form, with 3 separate modes of administration: self-administered subcutaneous injection, tablet, and nasal spray. The multiple-dose forms enable the physician to match the medication to the specific characteristics of the attack. Sumatriptan has the lowest lipophilicity of the triptans. It has a relatively short plasma half-life (2 hours) and is extensively metabolized via first-pass metabolism in the liver by monoamine oxidase type A. The injection has a very short timeofoccurrence formaximumdrug concentration (tmax, 0.2 hour), with a fast onset of action starting at 10 to 15 minutes. Its extremely high bioavailability of 97% contributes to its efficacy of 50% at just 30 minutes after dosing, of 77% at 1 hour, and of more than 80% by 2 hours. It has a headache recurrence rate of 34% to 38% and a slightly higher rate of typical triptan adverse effects, such as nausea, paresthesias, flushing, and tight sensations. It is the preferred way of treating patients who vomit early in the course of their attack, as well as those whose pain reaches maximum intensity in less than an hour. Sumatriptan oral tablets have a bioavailability of 14%, with a tmax of 2.0 to 2.5 hours, producing a 2-hour response rate of 61% with the 50-mg dose. Studies using 100-mg tablets taken when the pain is mild have shown better response rates. Tablets have fewer adverse events, are easier to take, and are preferred by many more patients over either the injection or the nasal spray. The nasal spray form of sumatriptan is available in 5and 20-mg doses. It has a bioavailability of 17% and a highly variable tmax of 0.08 to 4.0 hours, with the shortest tmax resulting in a rapid onset of action, averaging 15 to 30 minutes, which is between that of the injection and the tablet. As many as 40% of patients respond in 30 minutes and as many as 63% in 2 hours. Some patients do not likethetaste,andirregularabsorption from the nose can cause nasal sumatriptan to enter the gastrointestinal tract, leading to inconsistentefficacy. To summarize, what makes sumatriptandifferent is the flexibilityof form, combined with the unmatched speedandpotencyoftheinjectionand the speed of onset of the nasal spray, both forms being faster in onset than all oral triptans. Zolmitriptan (Zomig) tablets are available in 2.5and 5.0-mg sizes. It is metabolized first by the cytochrome P-450 system, and then the active metabolite, which has a 50% longer half-life than the parent compound, is further broken down by monoamine oxidase type A. It has a tmax of 2.0 hours and bioavailability of 40% to 48%. It is more lipophilic than sumatriptan and has a 2-hour headache response rate of 62% to 67%, with a recurrence rate of about 30%. It has the best published consistency of all the triptans, with 95% of patients successfully treating their attacks with 1 or 2 doses of 2.5 or 5.0 mg in a long-term, open study. In that same study, a second dose of zolmitriptan given at 2 hours for persistent headache when the first dose failed resulted in a statistically increased likelihood of a pain-free response after the second dose. The zolmitriptan (Zomig ZMT) orangeflavored, orally disintegrating tablet was released in 2001. It has almost identical characteristics to the conventional zolmitriptan tablets but is more convenient, can be taken without water, and can be used when a patient has nausea. Thus, what makes zolmitriptan different from the other triptans is a proven ability to treat persistent headache when the first dose fails, resulting in the highest consistency of response over time, with 95% of attacks aborted at 2 hours with 1 or 2 doses of zolmitriptan over 1 year. Naratriptan(Amerge)isavailable asa1.0-and2.5-mgtablet.It isreferred toasthegentletriptan,asithasaslower onsetofactionandalowerrecurrence rate than both sumatriptan and rizatriptan, as well as a favorable adverse effectprofile.Ithasatmaxof2to3hours, a bioavailability of 63% in men and 74% in women, and is the most lipophilic of the available triptans. It has the longest half-life of the currently available triptans (5.0-6.3 hours). It has significant renal excretion and is also metabolized by several cytochrome P-450 enzymes, so it can be givenwithmonoamineoxidaseinhibitor antidepressants, without interaction. Headache response is 48% at 2 hours, but reaches 66% by 4 hours. NaratriptanpreventedmenstrualmiFrom The New England Center for Headache, Stamford, Conn, and the Department of Neurology, Yale University School of Medicine, New Haven, Conn. CONTROVERSIES IN NEUROLOGY