Paroxetine is a selective serotonin
re-uptake inhibitor. Because of its prevalence,
its clinical features (such as efficacy,
side-effects and withdrawal symptoms) are
well-known to clinicians. However, more subtle
sideeffects might not become evident. In regard
to this, this paper reports two cases of
excessive yawning as sideeffects of paroxetine.
Although to date there have been case reports of
excessive yawning induced by other types of
selective serotonin re-uptake inhibitors
(fluoxetine, citalopram, sertraline), to the
author's knowledge this is the first report of
paroxetine -induced excessive yawning.
CASE 1
The patient was a 21-year-old Japanese woman
who began treatment for symptoms of panic
disorder with 10 mg paroxetine orally after
every evening meal. The next day the patient
began to yawn excessively in the daytime without
feeling drowsy despite adequate sleep at night.
She also had difficulty when intentionally
stopping herself from yawning. Frequency of
yawning was greater in the morning than in the
afternoon. Then, 4 weeks after starting the
treaiment, the dose of paroxetine was decreased
to 5 mg. Consequently, the frequency of yawning
decreased by approximately half, but excessive
daytime yawning still continued. Six weeks after
starting the treatment. her symptoms
disappeared, so the treatment with paroxetine
was ended. As a result her excessive yawning was
resolved completely.
CASE 2
The patient was a 43-year-old Japanese woman
with symptoms of panic disorder. Treatment with
10 mg paroxetine orally after every evening meal
was started. Two weeks later, the dose of
paroxetine was increased to 20 mg. The day after
paroxetine was increased, excessive daytime
yawning occurred. The yawning was not associated
with sedation. The patient could not endure
yawning voluntarily. In this case, frequency of
yawning was greater in the morning and gradually
decreased in the afternoon. Seven days after
paroxetme was increased, because her symptoms
improved, the dose of paroxetine was decreased
to 10 mg again. Consequently, her excessive
yawning disappeared completely.
Although yawning is a phylogenetically old,
stereotyped event and a common physiological
event in humans and animals, the exact
neuropharmacological mechanism of yawning
induction has yet to be clarified because
various types of neurotransmitters and
neuropeptides interact in a complicated way. In
these cases, however, acute increases in central
serotonergic neuronal activity caused by
paroxetine might be involved in the phenomenon.
In particular, it is possible that failure of
serotonergic modulation of yawning' could be
caused by excessive stiniulation of the 5-HT2c
receptor induced by paroxetine in the synapses
in the brain area involved in control of yawning
(i.e. paraventricular nucleus, hippocampus, pons
and/or medulla oblongata).
Concerning the clinical features of
paroxetineinduced excessive yawning, it is
suggested that it is dose dependent, and that it
decreases with time course, that is, it seems to
be dependent on the concentration in the blood.
In addition, it appears not to be associated
with sedation or drowsiness, and it seems that
not only the frequency of yawning but also the
intensity of yawning are outstanding.
In conclusion, clinicians should be
aware that selective serotonin re-uptake
inhibitors such as paroxetine could evoke
excessive daytime yawning as a side-effect.
