The antidepressant imipramine is a
dibenzazepine tricyclic antidepressant. Its
mechanisms of action include blocking the
reuptake of both norepinephrine and serotonin at
the synaptic cleft within the CNS. Imipramine
also possesses anticholinergie properties and
seems to have little effect upon dopaminergic
systems within the CNS.
Many side effects from imipramine are knwn
and listed in the 1982
Physician'sDeskReference(PDR). However, search
of this reference and the index Médicus"
did not reveal any reports of spontaneous and
sustained periods of yawning, uncoupled from
sedation, and secondary to imipramine
administrat ion. In this report, the case of a
woman who had such periods of yawning after the
traetment of depression with imipramine is
presented.
CASE REPORT
Ms.A was a thirty-year-old unmarried woman
who sought psychiatric help because of the onset
of a major depressive episode. Her depression
began three months prior to consultation and was
precipitated by career changes and the loss of
her boyfriend. Ms. A described feeling sad,
hopeless, and helpless. She reported that her
depression was worse in the morning and was
accompanied by decreased appetite, several
pounds of weight loss, terminal insomnia,
decreased attentiveness, fatigue and
tearfulness. She denied any suicidal ideation,
hypomanic or manie episodes, medical illnesses,
or drug or alcohol abuse. The patient had no
prior psychiatric illness, although an older
brother had committed suicide ten years earlier,
and her father was an alcohol abuser. Ms. A's
physical and laboratory examinations were
normal. Dexamethasone suppression test was not
performed.
Because of Ms. A's major depressive episode,
she was treated with a regimen of imipramine, 50
mg b.i.d. This initial dosage was increased over
two weeks to imipramine, 150 mg b.i.d. At this
dosage level, Ms. A's imipramine blood level was
170 ng/ml (therapeutic range l~0-300 ng/ml), and
she experienced a dramatic alleviation of her
depression. She tolerated the medication well
and only complained initially about dryness of
her mouth, slightly blurred vision and
constipation. After three weeks treatment with
imipramine, 150 mg b.i.d., Ms. A reported the
occurrence of unusually long episodes of
yawning which she retrospectively observed
frorn treatment onset but which had worsened as
her dosage of imipramine was increased, The
yawning periods would begin spontaneously and
last from five to fîfteen minutes about
twice per day. Ms. A denied any signs of fatigue
or sedation during these periods. Just as'
spontaneously as her yawning would begin it
would end, leaving Ms. A with a feeling of
embarrassment, especially if others were
present. On one occasion, her yawning was
observed in a treatment session and did not
appear related to somnolence or boredom. Ms. A
had improved clinically; her medication dosage
was gradually decreased to imipramifie, 150 mg
q.d. for four months, and then eventually
discontimied. As the médidation dosage
was decreased, the periods of sustained.yawning
occurred less frequently (about once per day).
Yawning ended two days after the
medicâtion was terminated.
DISCUSSION
Yawning is a multiple motor act with many
causes and with an obscure mechanism in humans.
Borodom, anxiety, and sleepiness can all cause
yawning. Yawning can also occur in the presence
of intracranial disease and in the absence of
the above-mentioned states. For example, Ms. A
experienced periods of yawing uncoupled from any
sedative side effects of imipramine.
In neuropharmacological studies with rats and
cats, yawning is a behavioral response to drug
challenges which is carefully documented.
Yawning in. rats is facilitated by drugs which
stimulate dopaminergic or cholinergie activity
within the CNS, while in cats yawning is
inhibited by dopamine transmission, but
facilitate by serotonin activation. One case of
yawning as a drug induced effect to medication
in humans bas been reported. The patient was a
young man suffering from postanoxic action
myoclonus who received sodium valproate as
treatment. Shortly after drug initiation, the
patient developed yawning every two to three
minutes which appeared to be dose related to
sodium valproate. On the basis of familiarity
with the literature on yawning in rats it was
assumed that the yawning in this case was caused
by doparninergic activation secondary to sodium
valproate treatment. Pimozide, a potent dopamine
antagonist, was administered and yawning
abated.
The case of Ms. A is the first report of
yawning, uncoupled from sedation, as a side
effect of imipramine. The correlations between
initiation of imipramine treatment and the onset
of yawning, as well as between the reduction of
yawning with dosage decrease, suggest that
irnipramine was the cause of yawning.
Unfortunately, data concerning yawning and drug
rechallenge are not available.
Since imiprarnine has little effect upon
dopamine activation, another mechanism may be
responsible for the occurrence of yawning.
Perhaps serotonin, which causes yawning in cats
and whose reuptake is inhibited by imipramine,
may also play a role in yawning in humans. The
case of the young man treated with sodium
valproate for postanoxic action myoclonus can
lend some credence to this hypothesis despite
successful remission of yawning with pimozide
administration. The underlying mechanism for
postanoxic myoclonus is serotonergic deficiency.
In the case cited above, sodium valproate might
have acted upon serotonergic systems and
restored serotonin levels which subsequently
improved postanoxic action myoclonus and. caused
yawning. Suffice it to say that neither the rat
nor cat models for yawning maybe totally
applicable for humans.
If yawning is a side effect to imipramine, it
can go unreported by patients and yet be
troublesome enough for the patient to inhibit
medication compliance. Especially when
noncompliance is suspected by the clinician,
inquiry into the presence of sustained yawning
should be made.If a patient experiences this
side effect, he should be informed that it is
reveriible. When sustained yawing occurs, its
severity seems dose related and can be managed
by dose reduction if that is not clinically
contraindicated. In other instances, switching
antidepressant medication to one which is less
serotonergic than imipramine may eliminate this
problem and still provide alleviafion of
depression..
