Abstract and Key WordsTable 1: Duration of Triptan Use
Objective: This study examines the safety of daily or near-daily triptan
use over extended periods of time. For a small group of refractory migraine
plus chronic daily headache patients, the triptans are effective.
Methods: This retrospective study primarily evaluated the cardiac safety
of daily triptans in 118 patients and, in addition, hematologic tests were
assessed. Each patient had utilized a triptan for a minimum of 4 days/week, for
at least 6 months. Patients suffering from rebound had been withdrawn off of
the triptans. The majority (97/118) averaged 1 tablet daily; most would
occasionally go for several days without the triptan. Forty patients had
utilized the triptans for 6 months to 2 years, 37 patients from 2 to 4 years,
and 41 for 4 or more years.
Results: Routine hematologic tests were performed periodically on all
patients, and no abnormalities were attributable to the triptans. Almost
all patients had an ECG, and no abnormal ECG’s were felt to be related to
the triptans. 57/118 patients had a cardiac echocardiography. The 10 abnormal
echocardiograms were not due to triptans. All 20 cardiac stress tests
performed were normal. Adverse events were minimal; 9 patients described
fatigue due to triptans, and 5 had mild chest tightness.
Conclusions: This 118 patient long-term study indicates that
frequent triptan use may be relatively safe.
Key Words: Triptan, Chronic Daily Headache, Migraine.
Abbreviations: ECG - Electrocardiogram IHS - International
Many patients with migraine and chronic daily headache (cdh) are refractory
to the usual preventative medications. One previous study of patients with
cdh indicated that, over the long-term, only 46% would respond to
preventatives (1). The usual preventatives include antidepressants,
anticonvulsants, beta-adrenergic blocking agents, calcium channel
antagonists, and muscle relaxants (2). For those who continue to experience
moderate or severe headache on a frequent basis, medication choices are
limited. These include (among others) opioids (3), monoamine oxidase
inhibitors (4), botulinum toxin injections (5), or a combination of
A group of patients respond only to triptan medications (sumatriptan,
naratriptan, rizatriptan, almotriptan, zolmitriptan, frovatriptan,
eletriptan). The patients in this study were never instructed to utilize
triptans on a daily basis. They ‘self-discovered’ that a dose of the triptan
would alleviate the headache for most or all of the day. The vast majority
of patients in this study had a history of many years of headache,
refractory to the usual medications. They finally had found a medication
(the triptan) that alleviated the headache for some period of time.
One goal of this retrospective study was to evaluate the cardiac safety of
the triptans in this large group of patients. A secondary objective was to
assess the hematologic tests that were done in these patients.
Subjects and Methods
Subjects: One-hundred eighteen subjects (27 males and 91
females), ages 27 to 73 years (average age 52 years), were evaluated.
Inclusion criteria were: 1. The patient had utilized a triptan medication
for a minimum of 4 days weekly, for at least 6 months. 2. The triptan use
had to be consistent. All of the patients would occasionally go days
without the triptan. Exclusion criteria included: 1. Patients who were
felt to be suffering from rebound (they were withdrawn off of the triptan
prior to 6 months), and 2. Patients who were not utilizing the triptan at
least 4 days weekly, on a consistent basis.
Previous Medications: The patients were all long-term patients
at the Robbins Headache Clinic. Each patient had been refractory to at
least 3 of the usual preventative medications. These included
beta-adrenergic blocking agents, calcium channel antagonists,
antidepressants, anticonvulsants, methysergide, non-steroidal
anti-inflammatories (nsaids), and muscle relaxants. The majority of patients
had been refractory to 5 or more daily preventatives. During the study,
besides the triptan, most patients did continue on at least one preventative
medication, the most common of which were antidepressants. In addition, many
were also utilizing other abortive medications, besides the triptan. These
included nsaids, and other analgesics.
Rebound: The patients were carefully screened for the presence
of rebound headache. If the history was possibly consistent with rebound,
the patient was withdrawn off of the triptan.
Patient Assessment: The interviews and chart reviews were done
by the treating neurologist at the Robbins Headache Clinic. Hematologic,
electrocardiographic and echocardiographic findings were assessed via
retrospective chart reviews. In patients on daily triptans, as a matter of
routine (at this Clinic) hematologic tests were regularly done, as were
electrocardiographs. Cardiac echocardiography with doppler flow studies
were accomplished on 57 (almost half) of the patients.
Type of Headache: Headache classification was based on
International Headache Society (IHS) revisions proposed by Silberstein et
al (6). The diagnosis was migraine plus chronic daily headache in 107/118
patients, cdh alone in 2, and chronic cluster in 9.
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 taken the stated 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 occasionally take weeks off from the triptan).
|Number of Months on Triptan
||Number of Patients (Percentage of Total)
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. Table 2: Echocardiograms (done on 57/118 patients)
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. ECG’s were evaluated by a
cardiologist. 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: (See Table 2) Fifty-seven patients
were administered an echocardiogram with Doppler Flow Studies. 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.
|Number of Patients
||Results of Echocardiogram
||Mitral Valve Prolapse
||Mild Right Ventric. Enlargement
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
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.
In this current 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
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.
Our previous study assessed 59 patients with migraine plus cdh (7). As in
the current study, the patients had taken a daily (or near-daily) dose of
a triptan for a minimum of 6 months. These patients had selected daily
triptans because, after years of failing various preventative regimens,
they had finally found medications that were beneficial.
In the previous study (7), twenty-three patients (39%) had been on triptans
for 6 to 12 months, while 36 (61%) were on them for more than one year. The
patients had previously failed multiple first and second line preventive
medications. Forty-one patients (69%) were currently on preventive
medications; the most common preventives were sodium valproate and
antidepressants. Forty-five patients (76%) used abortive medications, in
addition to the daily triptans. While 39 patients (66%) had previously
overused abortives, they were not overusing them since being on daily
triptans. Side effects were minimal in this patient population. However,
as in the current study, since the patients self selected the daily triptan
use, side effects would be expected to be low in this population. Rebound
headache due to triptans was not encountered in this study, primarily
because those with rebound did not continue on the daily triptans. Blood
tests were done on all patients. Results were normal in 47 of the 59
patients, whereas 12 were abnormal. None of the abnormal test results were
felt to be due to the triptans. Electrocardiograms were normal in 19 of the
23 patients who had this procedure, while four were abnormal. The abnormal
ECG results were not felt to be due to the triptans. Echocardiography was
done on five patients and all were normal (7).
Short-lasting adverse events are often encountered with the use of triptans.
These include paresthesias, fatigue, chest heaviness, jaw or neck discomfort,
etc. (8, 9). The chest symptoms are, with rare exceptions, not of
cardiovascular origin. Cardiac ischemia due to triptan use is rare (10,11).
The triptans do constrict coronary vessels, but this is a mild and
short-lived effect. Despite widespread triptan use, the number of adverse
cardiac events has been limited (12). Echocardiography and
electrocardiography have generally been normal after triptan use, even in
the presence of chest symptoms (13,14).
The primary issue with frequent triptan use, assuming rebound headache is
not present, is long-term adverse events. The most likely system for possible
long-term sequelae would be cardiovascular. Chronic ischemic changes,
valvular abnormalities, or fibrosis are theoretical considerations. There is
no evidence to date that long-term use of frequent triptans does produce any
of these adverse events. However, this has not been systematically studied.
The number of patients throughout the world who have utilized near-daily
triptans is unknown. Until studies on these patients have been done, it is
reasonable and prudent to do cardiac monitoring, as well as hematologic
tests, on these patients.
While adverse effects from long-term triptan use are unknown, the
alternatives have potential problems. Many patients with cdh are overusing
analgesics, which have well-known adverse events (15). These include liver
dysfunction, GI bleeding, renal insufficiency, and addiction.
There are many headache patients who have been refractory to daily
preventative medications. The use of daily triptans offers a small number of
these patients an improved quality of life. We will need further studies to
evaluate safety of frequent triptan use.
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