Yawning is a common but complex stereotyped
reflex poorly understood. Different physiologic
(hunger, hypoglycaemia, sedation) and pathologic
(Eustachian tube disorders, travel sickness,
infectious diseases, neurological diseases,
iatrogenics) states can induce yawning. Among
drugs known to induce yawning, serotoninergic
agents are frequently cited, such as selective
serotonin reuptake inhibitors antidepressants
[1]. Yawning induced by other class of
antidepressants, such as noradrenalin and
serotonin reuptake inhibitors or imipraminic
antidepressants have also been described in
literature [2,3].
We report here the case of a young woman who
presented repetitive excessive yawning induced
successively by paroxetine, a selective
serotonin reuptake inhibitor, clomipramine, a
tricyclic antidepressant and Saint john's wort
(Hypericum perforatum). Interestingly, the yawns
regressed during agomelatine treatment.
Case report
An 18-year-old woman presenting depression
was first treated with minalcipran, a
noradrenalin and serotonin reuptake inhibitor
antidepressant. The treatment was well tolerated
but was stopped because of a lack of efficacy
and induced insomnia. Then, the patient received
a selective serotonin reuptake inhibitor,
paroxetine 20 mg daily, but, some days later,
she experienced abnormal excessive daytime
yawning lasting up to several seconds,
associated with contractures of the jaws.
These yawns were disturbing, and disabled
the patient while working and bothered her to
speak. Paroxetine was discontinued and her
yawning completely disappeared. Paroxetine was
replaced by a tricyclic antidepressant,
clomipramine 25 mg daily, which rapidly induced
the same symptoms. Clomipramine was stopped and,
as previously, yawning rapidly regressed. After
one week, this treatment was substituted by
Saint john's wort but yawning reappeared after
the first dose, and disappeared the day after
discontinuation. Agomelatine, a melatonin
receptors agonist, was then introduced, without
causing yawning after few weeks of therapy.
Discussion
Yawning is known to be under the control of
several neurotransmitters and neuropeptides,
such as serotonin, dopamine, acetylcholine,
nitric oxide, excitatory amino acids, ACTH and
oxytocin [4].
Yawning induced by serotonin reuptake
inhibitors antidepressants, such as paroxetine,
or tricyclic antidepressants, such as
clomipramine, is a rare but known adverse drug
reaction.
In 2007, Sommet et al. study the
observations of yawning in the French
Pharmacovigilance Database [1]. Among
the 38 reports recorded from 1985 to 2004, 12
involved serotonin reuptake inhibitors
(paroxetine n = 5, fluoxetine n = 4, sertraline
n = 3). The delay of occurrence ranged from 1
day to 8 weeks. Drug was withdrawn in 8 cases
and the resolution was observed in 9 cases. In
this study, the serotonin reuptake inhibitors
were the main pharmacological class involved,
followed by dopaminergic drugs, confirming the
implication of serotonin and dopamine on
yawning.
In the other cases reported in literature,
yawning appears during the days following the
introduction of the treatment, and regresses or
disappears after dose reduction [3,5-7].
Some case reports have suggested that yawning
behaviour might be dose-dependant.
Yawning is considered as an unwanted effect
during antidepressant therapy but for few
authors, it is considered as beneficial in the
regulation of brain homeostasis [8,9].
Indeed, there is a strong connection between
yawning and thermoregulation, and a yawn would
promote cerebral cooling. Thus, when serotonin,
a vasoactive compound implicated in
thermoregulation, induces brain and core
temperature, it is counterbalanced by excessive
yawning.
No case of yawning induced by Saint john's
wort is described in literature, but his
mechanism of action passing by the
serotoninergic way could explain his involvement
in this case.
Up to now, no case of yawning induced by
agomelatine is reported in literature, probably
because no direct action on 5HT increase is
associated with this drug. To note, this drug is
a melatonin receptor agonist (MT1-MT2) and a
5-HT2C receptor antagonist (but without effect
on extracellular serotonin concentrations).
All the treatments inducing yawning in this
patient were then acting on the serotonin
pathway, which confirms the role of this
monoamine in the mechanism of yawning. In
addition, the temporal relationships between the
episodes of yawning after the administration of
the drugs and especially the regression of the
symptoms after drug discontinuation comfort the
responsibility of these treatments.
The good tolerance of minalcipran, a
noradrenalin and serotonm reuptake inhibitor is
however surprising, but the posology (presently
unknown) was possibly low.
Conclusion
Yawning must be considered as a real
disabling adverse event of antidepressant drugs,
which could be a strong reason for
inobservance.
[2] Bertuchy
D, Vandel S, Sechter D, Bizouard P.
[Yawning and sexual excitation under
clomipramine. Role et serotoninergic mechanisms.
Apropos et 2 cases]. Encephale
1991;17:515-7.
[4] Collins
DL Eguibar JR. Neurophamacology et yawning.
Front Neurol Neurosci 2010;28:90-106.
[5] Pae
CD, Kim JJ, Lee CD, Lee SJ, Lee C, Paik JH.
Injured temporomandibular joint associated with
tluoxetine-monotherapy-induced repeated yawning.
Gen Hosp Psychiatry 2003;25(3):217-8.
[6] Harada
K. Paroxetine-induced excessive yawning.
Psychiatry Clin Neurosci 2DD6;6D:26D.
[7] Gutierrez-Alvarez
AM. Do your patients suffer from excessive
yawning? Acta Psychiatrica Scandinavica
2007;115(1)-80-81.
[8] Prasad
H. Drug-induced yawning: a vital protective
reflex. Med Hypotheses 2DD8;71:4S7.
[9] Gallup
AC, Gallup Jr GG Venlafaxine-induced
excessive yawning: a thermoregulatory connection
Prog Neuro Psychopharmacol Biol Pyschiatry
2009;33(4):747
