-Nayak R,
Bhogale GS, Patil NM Venlafaxine and
excessive yawning: is there any link? J
Neuropsychiatry Clin Neurosci. 2011
Spring;23(2):E56-7.
Introduction
Yawning is a complex stereotyped behavior
with unknown physiological functions. Excessive
yawning without a decrease of the arousal level
has been noted with various drugs (Sommet et
al., 2007). Almost all these treatments have a
central nervous system action.
Venlafaxine, a selective serotonin and
norepinephrine reuptake inhibitor (SNRI), is
prescribed for the treatment of major depression
and anxiety disorders. Although yawning was an
uncommon side effect of venlafaxine during the
premarketing and postmarketing clinical trials,
no cases of severe and disabling yawning have
been reported till now.
Case report
Mr. A was a 24-year-old man, with no
previous history of medical or psychiatric
disorders. He suffered from dysphoric mood, loss
of interest, difficulty in concentration, and
suicidal ideation for eight weeks and was
diagnosed with a first episode of major
depressive disorder.
The results of his physical and neurological
examinations were normal. Prior to the start of
antidepressant treatment, he was psychotropic
drug naïve. During antidepressant
treatment, he did not take any concurrent drugs
or herbal medication.
He began to receive 75 mg/day of venlafaxine
extended release (XR) for major depressive
disorder. After four weeks of 75 mg/day of
venlafaxine XR, the dose of venlafaxine XR was
increased to 150 mg/day due to inadequate
response. His depressive symptoms significantly
improved after two weeks of receiving
venlafaxine XR at 150 mg/day.
But he experienced excessive yawning
seven days following the increment of the
venlafaxine dose. The yawning was not associated
with drowsiness, yet he was unable to
intentionally stop himself from yawning. He had
more than 50 occurrences of yawning daily,
frequently in the morning.
He was disturbed by this effect, as the
yawning occurred during his daily activities and
interpersonal interactions. The patient worried
that others would interpret the yawning as a
sign of indifference or boredom.
At the patient's request, the dose of
venlafaxine XR was reduced to 75 mg/day and
yawning completely disappeared within three days
thereafter. His depressive symptoms did not
recur.
Discussion
Yawning is under the control of several
neurotransmitters and neuropeptides which
interact in a complicated way (Daquin et al.,
2001). Among these substances, the well known
are dopamine, serotonin, noradrenaline,
acetylcholine, excitatory amino acid, nitric
oxide, adrenocorticotropic hormone-related
peptides and oxytocin (Melis and Argiolas 1997;
Argiolas and Melis 1998).
Abnormal yawning is present in numerous
pathologies (neurological, psychiatric,
infectious, and iatrogenic disease) (Daquin et
al., 2001). In our case, a close temporal
relationshipwas noted between the onset of the
excessive yawning and the increased dose of
venlafaxine, as well as its remission and the
decrement of the medication. A dose-dependent
side effect of venlafaxine is the mostly likely
cause of excessive yawing in this patient.
In preliminary studies, up to 3% of patients
receiving venlafaxine reported yawning as a
dose-dependent side effect of treatment (package
insert of Effexor™). Depending upon the
dose, venlafaxine has different degrees of
reuptake inhibition of serotonin (most potent at
low dose), noradrenaline (moderate potency and
present at higher doses), and dopamine (least
potent and present at highest doses) (Muth et
al., 1991; Weikop et al., 2004).
In our case, the excessive yawning
disappeared with the reduction of the
venlafaxine dose. This might suggest that the
noradrenergic and dopaminergic mechanisms may
play a role in the relationship between yawning
and venlafaxine dosage. Antidepressants, in
particular serotonin reuptake inhibitors, are
drugs that have been implicated in yawning.
However, there is very little research on
this, because for most people receiving
antidepressants, yawning is not a serious
problem. To date, there are only a few case
reports of excessive yawning induced by
serotonin reuptake inhibitor antidepressants
(Beale and Murphree 2000; Harada 2006; De Las
Cuevas and Sanz 2007; Gutierrez-Alvarez 2007;
Sommet et al., 2007) and SNRI duloxetine (De Las
Cuevas and Sanz 2007). Pae et al. (2003)
presented an extreme case report of an injured
temporomandibular joint associated with
fluoxetine-induced repeated yawning.
Therefore, the frequency and intensity of
antidepressant-induced yawning in some patients
could be disturbing and disabling.
Conclusion
In conclusion, although the mechanism of
excessive yawning is not clear, clinicians
should notice that venlafaxine could evoke such
a disabling side effect. As in the present case
report, the side effect was dose-dependent and
was relieved by decreasing the dose.
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