Yawning is a frequent behavior with
circadian effects. Sometimes, its frequency is
very high and it is disturbing. However, there
is no evidence-based treatment for yawning.
This is a case report of a man with severe
yawning from about 2 years ago. Yawning reduced
after taking propranolol.
Current evidence suggests that propranolol
may decrease yawning through its
thermoregulation effect. It is worthwhile
conducting controlled clinical trials to study
whether propranolol is an effective treatment
for yawning.
1. Introduction
Yawning is an unresolved medical and
psychological problem. Central dopamine or
serotonin receptor agonists may induce yawning
in humans [1]. The antagonists of
dopaminergic and serotonergic receptors
selectively antagonize yawning induced by
dopamine or serotonin agonists [2].
Contagious yawning is suggested to be in
association with empathic processing
[3]. Yawning is correlated with migraine
headache [4]. Meanwhile, there is an
argument that yawning is a brain cooling
mechanism [4&endash;6]. There are some
behavioral, physiological and medical evidence
supporting the brain-cooling hypothesis
[7]. Temperature recordings by implanted
thermocoupled probes in the frontal cortex of
rats show that yawns and stretches occur during
increases in brain temperature [8].
Many studies about yawning behavior were
conducted in animals. It is suggested that
intraperitoneal injection of
physostigmine-induced yawning in rats is
decreased by alpha1- and alpha2-adrenoceptor
stimulation. However, propranolol does not
decrease physostigmine-induced yawning in rat
[9]. Others reported that propranolol
increased physostigmine-induced yawn in rats
[10,11]. Only one study was found that
reported the association of landiolol, a
beta1-adrenoceptor antagonist, and yawning in
humans. It reported that beta 1-adrenoceptor
antagonist decreased the thiopental-induced
yawning response [12]. To the best of
the author's knowledge, the role of propranolol,
a nonselective beta blocker, for treatment of
yawning has never been reported before.
2. Case report
R.D. is a 48-year-old highly educated man.
He referred to clinic with depression, sadness,
thought preoccupation, lack of refreshing sleep,
irritability, decreased concentration, memory
impairment and a significant decreased personal
and occupational function level about 3 months
ago. He reported that he was suffering from
these symptoms from about 1.5 to 2 years ago. He
had referred to psychiatrist and he had taken
fluoxetine 20 mg/day for 2 months. He felt that
his problems were markedly decreased and he
discontinued the medication. There was not any
remarkable finding in physical and laboratory
examination. Positive history for general
medical condition such as epilepsy was
unremarkable. He denied abuse of any medication
or substance. He did not used to take coffee. He
does not smoke. The patient did not suffer from
obstructive sleep apnea syndrome and migraine
headache. There was no positive history for
remarkable head trauma. He had headache episodes
during his depression period. His headache and
yawning disappeared concurrently. Yawning was
not related to his sleep duration. However,
stress and anxiety enhanced yawning.
He reported that he used to yawn frequently.
Yawning started from about 2 years ago. Its
severity was more when he felt to be more
depressed and sad. Yawning was not related to
any specific time or place. The score of yawning
on a visual analogue scale decreased from 10 to
5 during taking fluoxetine. Then, he stopped
fluoxetine. Yawning severity increased after
discontinuation of fluoxetine. He was diagnosed
as a case with major depressive disorder.
Therefore, sertraline (100 mg/day) and
propranolol (40 mg/ day) were administered since
3 months ago. He reported that yawning
dramatically reduced in a few days after the
administration of the medications. Its severity
decreased from 10 to 0&endash;1. He has
continually taken sertraline for the last 3
months. Now, he is in the remission phase of
major depressive disorder. He was advised to
stop propranolol. He stopped it. But yawning
immediately reappeared. He restarted taking
propranolol again. These trials and stops of
propranolol administration were repeated several
times. Yawning remitted and reappeared after
administration and discontinuation of
propranolol in all of these trials,
respectively. He provided his informed consent
for publication of this report.
3. Discussion
To the best of the author's knowledge, there
was not any published clinical trial found for
treatment of yawning. Therefore, evidence-based
information is required for treatment of
yawning. There is evidence that propranolol is
effective for prevention of migraine headache
[13]. It is speculated that yawning is a
symptom related to some types of migraine
headache. One explanation for the role of
propranolol in this patient is that propranolol
prevented headache and its related symptoms.
However, yawning reoccurred after discontinuing
of propranolol, while headache did not come
back. In every trial, yawning remitted after
administering propranolol. This supports the
possible role of propranolol for the treatment
of yawning. In a case report, it is shown that
excessive yawning is triggered by mild
hyperthermia and that following bouts of yawning
body temperature, as measured by an oral
thermometer, actually reduced by 0.4°C
[14]. It is consistent with the view
that propranolol may diminish yawning frequency
by reducing brain and/or body temperature.
Moreover, propranolol reduces centrally mediated
fevers after traumatic brain injury [15]
and decreases skin temperatures [16].
Furthermore, propranolol prevents psychological
stress-induced elevation in body temperature
[17]. In addition, injected propranolol
into the cerebral ventricles of the mouse
reduces body temperature [18]. The
above-mentioned evidence supports the hypothesis
that propranolol may reduce yawning frequency
through its brain-cooling effects. It is
important that this patient took fluoxetine and
sertraline, which are selective serotonin
reuptake inhibitors used to treat depression.
These medications increase brain temperature and
produce excessive yawning [19,20].
However, it should be explained why propranolol
decreases yawning in humans while propranolol
rather increases or does not decrease
physostigmine-induced yawning in rats
[9]. Is this dissociation only due to
species-related differences? Is pathophysiology
of physostigmine-induced yawning in rats
different from yawning in human? It seems
worthwhile conducting controlled clinical trial
to investigate the possible therapeutic role of
propranolol for the treatment of yawning.
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