Letters to the Editor

Olmesartan, Migraine, and Blood PL Tokyo Health Care Center

Tokyo, Japan
Pressure

To the editor:
We read with great interest the article by Charles et al REFERENCE
concerning prophylactic treatment of migraine with olmesar- 1. Charles JA, Jotkowitz S, Byrd LH. Prevention of mi-
tan, wherein 22 of their 24 patients experienced a significant graine with olmesartan in patients with hypertension/
improvement in the frequency and the severity of migraine prehypertension. Headache. 2006;46:503-507.
attacks.1 The reduction in the frequency of migraine attacks
was 82.5% and the average reduction rate of headache inten-
sity was 45%. No serious adverse events were recorded and
the mean decline of systolic and diastolic blood pressures Neuroendocrine Derangement in
were 21 and 15 mmHg, respectively. Chronic Migraine
We have some limited experience with olmesartan ad-
ministered to migraineurs with both hypertension and nor-
To the editor:
mal blood pressure. After treatment with olmesartan (20 mg
Two reports that recently appeared almost simultane-
daily), both hypertensive and normotensive migraineurs ex-
ously in the headache literature both addressed a highly
hibited a decrease in migraine days and intake of analgesic
topical issue, namely the relationship between chronic
drugs, severity of headache, and functional disability also
migraine (CM) and stressful events.1,2 Both underscore
were ameliorated in both patient groups. Blood pressures
the need for scientific data regarding hormonal varia-
declined to normal in all hypertensive migraineurs and nor-
tions induced by stress and their relationship to disor-
motensive migraineurs exhibited no significant changes in
ders that may or may not evolve toward a chronic state
blood pressure. There were no adverse effects of olmesartan
(eg, migraine).
in our patients.
In the study by Rainero et al, the pathophysiology
Thus, our own preliminary observations concur with
of hypophyseal endocrine function in CM was evaluated,
those of Charles et al in suggesting that olmesartan can be
along with hypothalamis-pituitary axis activation through
effective in reducing migraine frequency and severity and
the study of cortisol’s direct involvement.1 Similar to their
is tolerated well in both normotensive and hypertensive pa-
results, in the study conducted by our investigative group in-
tients. We agree with the conclusion by Charles et al1 that
volving patients with CM and medication overuse headache
large randomized clinical trials are needed to evaluate the
(MOH), adrenocortical hyperactivity also was observed, dis-
safety and utility of olmesartan in migraineurs.
tinctively present during both day and evening, without sig-
nificant variations in cortisol’s typical circadian rhythmic-
Yasuo Iwasaki, MD ity or levels of dehydroepiandrosterone-sulfate (DHEA-s)
Professor of Neurology and testosterone.2 In both the reports, the respective au-
Toho University thors stressed the difficulty of distinguishing between cause
Medical Center and effect in regards to cortisol’s place in CM. While cortisol
Omori Hospital hyperactivity conceivably may follow clinical worsening of
Tokyo, Japan migraine, simply appearing as an epiphenomenon, it is well
Ken Ikeda, MD, PhD known that chronic exposure to high levels of glucocorticoids
Director and Professor of Neurology can itself produce neurotoxic effects.3

1309
1310 September 2006

In our study, data obtained through the measurement
of both testosterone and DHEA-s in relation to levels of
cortisol made it possible to evaluate CM in the context of 2
central parameters widely used in research involving stress.
These parameters could represent important biologic mark-
ers for monitoring the general psychophysiologic well-being
of the subject migraineur. Our second method of measure-
ment was entirely noninvasive and based on a simple but
reliable process made all the more attractive, because sali-
vary levels reflect better than those in plasma the hormone
serum fraction that is biologically active.4,5
Since in both Rainero et al’s and our own study of
adrenal hyperactivity in CM, it has been demonstrated that
a logical next step would involve an investigation of the op-
erative cause–effect paradigm of this relationship. Such an
assessment might be accomplished by measuring adrenocor-
tical activity (reflected via levels of salivary cortisol, DHEA-
s and testosterone) in patients afflicted with CM and MOH
who then underwent detoxification and reverted to the clin-
ical phenotype of episodic migraine.
Francesca Romana Patacchioli, MD
Paolo Martelletti, MD
Department of Human Physiology
and Pharmacology “V. Erspamer”
Sant Andrea Hospital
Rome, Italy
Department of Medical Sciences
2nd School of Medicine
Sant Andrea Hospital
Rome, Italy
REFERENCES
1. Rainero I, Ferrero M, Rubino E, et al. Endocrine function is
altered in chronic migraine patients with medication overuse.
Headache. 2006;46:597-603.
2. Patacchioli FR, Monnazzi P, Simeoni S, et al. Salivary
cortisol, dehydroepiandrosterone sulphate (DHEA-S) and
testosterone in women with chronic migraine. J Headache
Pain. 2006;7:90-94.
3. Sapolsky RM. Stress glucocorticoids, and damage to the ner-
vous system: Current state of confusion. Stress 1966;1:1-19.
4. Giubilei F, Patacchioli FR, Antonini G, et al. Altered circa-
dian cortisol secretion in Alzheimers’s disease. Clinical and
neuroroadiological aspects. J Neurosci Res. 2001;66:262-265.
5. Patacchioli FR, Monnazzi P, Scontrini E, et al. Adrenal dis-
regulation in amyotrophic lateral sclerosis. J Endocrinol In-
vest. 2003;26:23-25.