INTRODUCTION
Chronic daily headache (cdh) is often refractory to the usual preventative medications. Intolerable adverse events or lack of efficacy limit the standard preventatives. Analgesic overuse is observed in many cdh patients. Refractory cdh patients often become addicted to short-acting narcotics. For those patients with refractory cdh who experience moderate or severe daily headache, triptans offer one option. The other options for this group of patients include, among others, monoamine oxidase inhibitors, long-acting opioids, botulinum toxin injections, and stimulants.
The patients in this study discovered, on their own, that the triptans were highly effective for the daily headaches. These patients were not deliberately placed on daily triptans, and attempts to limit use had failed because the patients reported significant improvement in quality of life, usually after many years of suffering. They had been refractory to the usual cdh preventative medications.
Long-term effects of frequent triptan use are unknown. This study analyzed cardiac and hematologic exams in a large number of patients who had been utilizing triptans on a frequent basis.
MATERIALS AND METHODS
STUDY DESIGN: There were 118 patients in this study, ages 27 to 73, all long-term patients at the Robbins Headache Clinic. These patients had been refractory to the usual preventative medications for cdh and migraine. Each patient had utilized (at various times) at least 3 preventative medications. Chart review and patient interviews were conducted by the treating neurologist.
Each of the patients had used a triptan for at least 4 days per week, for at least 6 months. The course of triptan use varied from patient to patient; some would use 1 per day, others would use the triptan 4 days per week, but more than one per day on many of those days. Some patients took a break for one or two weeks during the course of therapy, but the majority were consistent with their triptan use.
TYPE OF HEADACHE: Headache classification was based on International Headache Society (IHS) revisions proposed by Silberstein et al. The diagnosis was migraine plus chronic daily headache in 107/118 patients, cdh alone in 2, and chronic cluster in 9.
REBOUND AND TOLERANCE: All of the patients were screened for the possibility that the triptans were actually causing headaches; if rebound was felt to be a possibility, the medication was discontinued. Some patients become tolerant to one type of triptan; the triptan was then discontinued for a period of time, or another similar one was substituted.
TYPE OF TRIPTAN: During the course of therapy, most patients switched from one triptan to another, and often reverted back to the original one. Reasons for this included tolerance, and insurance issues.
For the following, the patients had to be utilizing the listed triptan for at least 2 months: 85 patients used sumatriptan, 68 naratriptan, 37 rizatriptan, 30 zolmitriptan, and 6 almotriptan.
AMOUNT OF TRIPTAN: For most of the course of their therapy, the vast majority (97/118) of patients averaged 1 tablet daily (50 mg sumatriptan, 2.5 mg naratriptan,10 mg rizatriptan, 5 mg zolmitriptan). 8 patients used only ˝ tablet daily, while 8 used 1.5 tablets on a daily basis. Five patients consumed 2 tablets daily. 90 of the patients used the triptan every day, while 28 patients averaged 4 to 5 days per week. All of the patients would occasionally go for several days without the medication, or sometimes take weeks off from the triptan.
DURATION OF TRIPTAN USE:
Table I
# of Months
on the Triptan
|
Number of Patients
(% of Total) |
| 6-12 |
18 (15%) |
| 13-18 |
9 ( 8%) |
| 19-24 |
13 (11%) |
| 25-30 |
9 ( 8%) |
| 31-36 |
11 ( 9%) |
| 37-42 |
11 ( 9%) |
| 42-47 |
6 ( 5%) |
| 48-53 |
10 ( 8%) |
| 54-60 |
9 ( 8%) |
| 61-66 |
3 ( 3%) |
| 67-72 |
7 ( 6%) |
| 73-78 |
12 (10%) |
By combining the above groups, from 6 months to 2 years, there were 40 patients, from 2 to 4 years there were 37 patients, from 4 to 6 years there were 28, and 13 patients took the triptans for more than 6 years. 41 of the patients had utilized the daily triptans for 4 or more years.
RESULTS
LABORATORY (HEMATOLOGIC) TESTS: Routine blood tests were performed regularly on all patients, usually every 6 to 9 months. These included complete blood counts, and complete chemistries including liver and kidney functions, as well as cholesterol. 32 patients had an increased cholesterol, 12 patients had increased liver enzymes, and 3 had anemia. 2 patients had an increased blood urea nitrogen, and one had a decrease in platelets. None of the laboratory abnormalities was felt to be due to the triptans.
ELECTROCARDIOGRAMS (ECG): 103 patients were administered an ECG, of which 95 were normal. The ECG’s were done after prolonged triptan use by the patient, a minimum of 6 months after the onset of daily triptan therapy. Most patients had an ECG during the calendar years 2001 or 2002, which was toward the end of this study time period.
No abnormalities were felt to be related to the triptans. The following were the abnormal ECG findings (8 patients): atrial fibrillation, 1 patient; tachycardia, 2 patients; bradycardia, 1 patient. In addition, inverted t waves, 1 patient; non-specific st-t wave changes, 2 patients; and rare premature atrial contractions, 1 patient.
ECHOCARDIOGRAM WITH DOPPLER: 57 patients were administered an echocardiogram with Doppler. The echocardiograms were done after prolonged use of triptans by the patient, a minimum of nine months after the onset of daily triptan therapy. Most patients had an echocardiogram during the last 1.5 years of this study .
Table 2
(Echo’s done on 57/118 pts.)
| # of Patients
|
Results |
| 47 patients |
Normal |
| 6 patients |
Mitral Valve Prolapse |
| 1 patient |
Mitral Regurgitation |
| 1 patient |
Enlarged Aorta |
| 1 patient |
Mild Right Ventric.
Enlargement |
| 1 patient |
Aortic Regurgitation |
For those 10 patients with an abnormality on the echocardiogram, the patient had an evaluation by the attending cardiologist or internist. None of the abnormalities found on echocardiography was felt to be due to the use of the triptans.
CARDIAC STRESS TESTS: 20 patients had cardiac stress tests; all were normal. The stress tests were done for various reasons, unrelated to the triptans. One patient had a cardiac catheterization, which was normal.
ADVERSE EVENTS: 9 patients felt that the triptans contributed to fatigue. 5 patients had mild chest tightness, at times, possibly due to the triptans. Cardiac disease was ruled out in these patients. 3 patients felt that the triptans contributed to nausea.
Because this was a group of patients who decided on their own to utilize the triptans on a daily basis, adverse events would be expected to be low. If patients were not tolerating the medication well, or were having significant adverse effects, they would not choose to continue the triptan on a frequent basis.
CONCLUSION: In this study, there were no adverse consequences discovered from the utilization of frequent triptans, over a prolonged period of time. 118 patients (primarily with migraine and cdh) had ‘self-selected’ triptans as the only beneficial therapy for their daily headaches. These patients had been refractory to the usual chronic daily headache and migraine preventatives.
Examinations utilized in this study included ECG’s, echocardiography with doppler, and laboratory blood tests. There may be adverse consequences of daily triptan use that were not detected in this study.
We are many years and many studies away from advocating ‘routine’ use of triptans on a frequent or daily basis. Long-term safety remains unknown. However, the limited evidence available suggests that triptans may be relatively safe over prolonged periods of time. These refractory cdh and migraine patients will often overuse analgesics, both otc and prescription. There are long-term consequences from the overuse of these medications. Therefore, in selected refractory patients it may be less injurious to the body to utilize triptans than large doses of analgesics.
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