Objective: Yawning has been
described in relation to drugs such as serotonin
reuptake inhibitors, levodopa, dopamine
agonists, MAO B inhibitor, morphine, methadone,
buprenorphine, dextromethorphan, benzodiazepine,
lidocaine, and flecaine. This is a report of two
patients, on long-term escitalopram therapy
(more than 8 weeks) with stable dosing, who
presented excessive yawning. Escitalopram is
widely used in major depressive disorder and
generalized anxiety disorder.
Method: A clinical description
of two cases.
Results: Two females (62 and 59
years old, respectively) developed excessive
daytime yawning. It was not associated with
sedation or a feeling of needing sleep. The
dosage was reduced and yawning disappeared some
hours later. The patients' depression did not
recur.
Conclusion: Yawning has been
described in relation to different selective
serotonin reuptake inhibitors and remitted
following their discontinuation; it is
interesting that the reported yawning in these
two cases disappeared with the reduction of
dosage, rather than the interruption of
treatment.
Introduction
Escitalopram oxalate, the S-enantiomer of
racemic Citalopram, as one of the newer
antidepressant agents, is an orally administered
selective serotonin reuptake inhibitor (SSRI)
considered to be better tolerated more than
older tricyclic antidepressants and monoamine
oxidase inhibitors. The newer antidepressant
medications also have significant side effects
from stimulation of 5-HT2A, 5-HT2C and 5-HT3,
from noradrenergic receptor stimulation, as well
as from interactions at other receptors
including muscarinic, histaminergic, and
postsynaptic a1-adrenergic (1, 2). Not many of
these side effects are easily recognized.
Clinicians should listen carefully to their
patients when they describe an unexpected
reaction, in order to ensure that it does not go
unnoticed. This is a report of two cases in
which excessive daytime yawning was associated
with escitalopram treatment.
Case 1
Mrs I is a 62-year-old woman who began
treatment for a minor depressive episode
(DSM-IV) (3) with the recommended dose 10 mg/d
escitalopram. Her depression responded rapidly
to treatment, however, following 2-month's
therapy; she began to experience excessive
daytime yawning. The patient estimated that
yawning occurred during 1 or 2 h, every morning.
The yawning was not associated with sedation or
a feeling of needing sleep. She was disturbed by
this effect, as yawning occurred
during her daily activities and
interpersonal interactions.
This led the patient to become concerned
that others would interpret this as a sign of
boredom or lack of attention and interest. At
the patient's request, the dosage was reduced to
5 mg/d and yawning quickly disappeared 24 h
later. The patient's depression did not
recur.
Case 2
Mrs M is a 59-year-old woman who bega
treatment for a minor depressive episode with 10
mg/d escitalopram. Following 2-month's
treatment, she began to experience daily yawning
episodes, at the same time as Mrs I for an hour
or so. This was very distressing, as the yawning
occurred in the presence of clients and
co-workers. Frequently, her husband made
comments regarding Mrs M's yawning. This was so
bothersome to her that, at her request, a
reduction in the dose was necessary. The
excessive yawning remitted within 2 days and has
not recurred.
Discussion
Yawning is a stereotyped event with unknown
physiological functions. It is under the control
of several neurotransmitters and neuropeptides:
dopamine, excitatory amino acids, acetylcholine,
serotonin, nitric oxide, adrenocorticotropic
hormone- related peptides and oxytocin that
facilitate yawning and opioid peptides that
inhibit this response. Abnormal yawning is
present in numerous pathologies (neurological,
psychiatric, iatrogenic, and infectious disease)
(4). As we become more experienced with the
longterm use of SSRIs, more subtle side effects
may become evident. Clinicians may be aware of
yawning as a side effect of antidepressant
therapy; however, sparse literature exists on
the topic.
Yawning has been described in relation to
three different SSRI agents (fluoxetine,
citalopram, and sertraline) and remitted
following SSRI discontinuation (5, 6).
In the two cases presented here, yawning
seemed to be particularly frequent and
bothersome; insomnia or sleep difficulty was not
associated with the excessive yawning nor was a
sense of daytime sedation or sleepiness. Usually
patients report daytime sleepiness as a side
effect. In preliminary studies, up to 2% of
patients receiving escitalopram for generalized
anxiety disorder reported yawning as a side
effect of treatment, compared with 1% taking
placebo (inserto LexaproTM, 2005). Although the
mechanisms of the excessive yawning remain
unclear, in these cases; however, a serotonergic
mechanism may have played a role. An exact
mechanism of yawning induction seems to be
difficult to understand and conflicting data
exist regarding the role of specific
neurotransmitters.
Comparing these cases with previous reports,
mainly a French study (7), in which they found
involved drugs such as SSRIs (13), levodopa
(three) dopamine agonists (three), MAO B
inhibitor (one), morphine (one), methadone
(one), buprenorphine (one), dextromethorphan
(one), benzodiazepine (four) lidocaine (two),
and flecaine (one). Occurrence of yawning
largely varied from 30 min to several months
after drug introduction and evolution was
usually favorable after drug withdrawal; it is
interesting that the reported yawning in the
previous two cases disappeared with the
reduction of doses rather than the interruption
of treatment. This is a positive thing that
encourages using the antidepressant and
continuing with it even though the patient can
report the yawning episodes.
Regarding the relationship between yawning
and dosage, this might suggest that differences
in escitalopram-induced yawning could be due to
individual vulnerability. These cases highlight
the current problems that can be associated with
newer antidepressants. Intolerance of newer
antidepressant agents continues to be a
significant cause of treatment failure, despite
the common belief that these medications are
better tolerated (8, 9). It will be useful to
remember that yawning requires the same clinical
attention as other symptoms, and has proved to
be a valuable tool in studying the
physiopathology of diseases and the action of
new drugs in humans.
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