- It has been identified but is not well-known
or appreci- ated by practitioners that selective
serotonin reuptake inhibitors (SSRIs) can cause
excessive yawning as a side effect. SSRIs
are the treatment of choice for depression. The
list of approved indications for these drugs has
expanded to include obsessive-compulsive
disorder, social anxiety disorder, generalized
anxiety disorder, premenstrual dysphoric
disorder, and eating disorders.
-
- Gastrointestinal side effects, sexual
dysfunction, and headache are the most common
adverse effects seen with the use of these
drugs. We report a case of a man who developed
excessive yawning secondary to treatment
with citalopram. A substantial amount of money
was spent to treat his yawning before it
was recognized that it could be a side effect of
a medication.
-
- Case report.
- Mr. A, a 58-year-old married white man with
major depressive disorder, was admitted in
December 2005 at the Comprehensive Epilepsy
Center for electroencephalogram (EEG) monitoring
to rule out epilepsy as a cause of excessive
yawning.
-
- Mr. A‚ yawning spells had
started several months previously and had become
worse during the last couple of months. His
estimated frequency of spells was 10 to 20 per
day, with each spell lasting 10 to 30 minutes,
and he would yawn 20 to 50 times per spell.
Yawning spells would cause him to be
lethargic, dizzy, and sometimes drowsy. These
spells would come at any time and anywhere
without warning. `
-
- He found them distressing, embarrassing, and
bothersome, so he decided to seek help from his
pri- mary physician, who did an initial
evaluation and referred him to a neurologist to
rule out a neurologic cause. Mr. A had had a
transient ischemic attack a year before his
December 2005 admission, from which he had fully
recovered, and the neurologist recommended EEG,
magnetic resonance imaging of the head with
contrast, magnetic resonance angiography of the
head, and Doppler studies of carotid arteries to
rule out stroke, epilepsy, or tumor as a cause
of excessive yawning.
-
- The results of all these studies were
unremarkable. A cardiologist was also consulted
to rule out a cardiac cause as the patient had a
history of atrial fibrillation and 1 episode of
chest pain. The cardiologist advised
electrocardiogram, echocardiography, and
angiography; these studies revealed no
abnormality. Since this extensive workup could
not point out the cause of the patient's
excessive yawning,
-
- Mr. A was next referred to the
epileptologist for EEG monitoring to rule out
temporal lobe epilepsy. Mr. A was admitted to
the EEG monitoring suite for 5 days; continuous
EEG monitoring and telemetry were performed, and
prolactin levels were measured with each
yawning spell.
-
- Electroencephalogram monitoring did not show
epileptiform discharges, and prolactin levels
stayed within normal range; tel- emetry showed
sinus bradycardia ranging from 40 to 60 beats
per minute with each spell. Complete blood cell
count, compre- hensive metabolic profile,
international normalized ratio (INR), and
urinary analysis results were also within normal
range. The medications he was taking at the time
of admission were citalopram 20 mg/day for major
depressive disorder, flecainide 50 mg every
morning and 100 mg daily at bedtime for atrial
fibrillation, and warfarin 5 mg/day. His
depression was controlled well with citalopram,
and atrial fibrillation was under control with
flecainide.
-
- Mr. A denied using illicit drugs and
admitted drinking socially. On further
questioning, the patient explained that his
yawning began within 1 to 2 weeks of
starting citalopram at 10 mg a day. It was not
bothersome to him until 2 months previously when
the dose of citalopram was increased to 20
mg/day for uncontrolled depression. His
depression had responded well to the increased
dose of citalopram, and he denied any daytime
drowsiness.
-
- During this hospitalization, epilepsy was
ruled out, and ex- tensive neurologic and
cardiac workup ruled out other neurologic and
cardiac causes of excessive yawning;
normal test results for electrolytes, liver
panel, and renal panel ruled out liver or renal
disease. SSRIs can rarely cause excessive
yawning; thus, at the time of discharge
from the hospital, we advised the patient to
taper off citalopram gradually and to begin
treatment with a non-SSRI antidepressant under
the supervision of a psychiatrist.
-
- After discharge, Mr. A tapered himself off
citalopram treatment slowly over 2 weeks. With
the weaning off of the dose of citalopram, his
excessive yawning diminished and
eventually stopped as citalopram was
discontinued. Upon follow-up after 1 month of
discontinuation of citalopram, Mr. A reported
being free of excessive yawning.
-
- On further follow-up after 2 months, he
continued to be free of excessive
yawning, but his depression had relapsed.
We followed up with the patient on the telephone
2 years after initial contact. He continued to
be free from excessive yawning. He denied
any depression at that time and had not taken
any antidepressant in the interim. Various
causes of excessive yawning are presented
in Table 1.
-
- In this case, the patient's excessive
yawning occurred with the introduction of
citalopram 10 mg/day but it was not bothersome
to him until citalopram was increased to 20
mg/day; his excessive yawning remitted
following discontinuation of citalopram. Beale
and Murphree report 2 cases of excessive
yawning with SSRIs. In the first, a
patient was started on treatment with fluoxetine
10 mg/day for major depression, developed
excessive yawning following 1 to 2 weeks
of therapy, and remitted on discontinuation of
fluoxetine; excessive yawning resumed
following citalopram 10 mg/day initiation and
stopped on dis- continuation of citalopram. In
the second case, a patient who was started on
treatment with 50 mg/day sertraline for major
depressive disorder also developed excessive
yawning within 1 to 2 weeks after
initiation of therapy, and his yawning
remitted within 1 week of discontinuation of
sertraline. In both cases, bu- propion was
started, and excessive yawning did not
recur with bupropion therapy.
-
- In a 6-week placebo-controlled trial using
citalopram (N=1,063) and placebo (N=446), 2% of
participants in the citalopram arm developed
yawning, compared to <1% of patients
taking placebo. In another study, 7% of patients
with obsessive- compulsive disorder, 11% of
patient with bulimia, and 1% of patients with
panic disorder receiving fluoxetine reported
yawning as a side effect of treatment,
compared with 0% of patients receiving
placebo.
-
- In a study by McLean et al.,
clomipramine-induced yawning in humans
was reported. In another study by Mogilnicka et
al., yawning in rats treated with
desipramine was documented.
-
- According to Goessler et al., the
hypothalamus and hippocampus in the brain play
an important role in yawning. Research
has shown that yawning is largely
affected by dopamine. Some other
neurotransmitters involved are nitric oxide,
serotonin, norepi- nephrine, acetylcholine,
glutamate, Œ³-aminobutyric acid, oxytocin,
and other neuropeptides; these have been shown
to increase yawning when injected into
the hypothalamus of animals.
-
- This case demonstrates that SSRIs can be
associated with a bothersome side effect of
excessive yawning, and this has been
described in the literature with different SSRIs
in varying incidences. If practitioners
recognize this association, expensive and
extensive workups may be prevented.
-
- REFERENCES
- 1. Beale MD, Murphree TM. Excessive yawning
and SSRI therapy. Int J Neuropsychopharmacol
2000;3(3): 275-276
- 2. McLean JD, Forsythe RG, Kapkin IA.
Unusual side effects of clomip- ramine
associated with yawning. Can J Psychiatry 1983;
28(7): 569-570
- 3. Mogilnicka E, Wedzony K, Klimek V, et al.
Desipramine induces yawning behavior in rats.
Neuropharmacology 1986; 25(7): 783-786
- 4. Prozac (fluoxetine). Physicians' Desk
Reference. Montvale, NJ: Thompson;
2006:1776
- 5. Goessler UR, Hein G, Sadick H, et al.
Physiology, role, and neuro- pharmacology of
yawning [in German].
Laryngorhinootologie 2005; 84(5): 345-351
-
-
- Table 1. Causes of Excessive
Yawning
- Epilepsy
- Encephalitis
- Brain tumors
- Stroke
- Multiple sclerosis
- Progressive supranuclear palsy
- Opiate withdrawal
- Heart attack
- aortic dissection
- Liver failure
- renal failure
- Drugs: selective serotonin reuptake
inhibitors, clomipramine, desipramine,
antiparkinsonism drugs
-
- Yawning
as a side-effect of antidepressant
therapy
- Le
bâillement, un effet secondaire
des traitements
antidépressifs
-
- Pathological
yawning in a patient with anxiety and chronic
disease anaemia
- Taskapilioglu O, Akkaya C, Sarandol A, Kirli
S. J Psychopharmacol 2008
-
- Duloxetine-induced
excessive disturbing and disabling
yawning
- De Las Cuevas C, Sanz EJ J
Clin Psychopharmacol.
2007;27(1):106-107
-
- Do your
patients suffer from excessive
yawning?
- Gutierrez-Alvarez AM Acta
Psychiatrica Scandinavica
2007;115(1)-80-81
-
- Paroxetine-induced
excessive yawning
- Harada KI Psychiatry
Clinical Neurosciences 2006; 60: 260
-
- Excessive yawning and
SSRI therapy
- Beale MD. Murphree TM. Int.
J. Neuropsychopharmacol. 2000; 3:
275-276.
-
- Fluoxetine-induced
yawning and anorgasmia reversed by
cyproheptadine treatment.
- Cohen AJ J. Clin. Psychiatry
1992: 53: 174.
-
- Repeated
observations of yawning; clitoral engorgement;
and orgasm associated with fluoxetine
administration
- Klein DF Clin
Psychopharmacol 1989; 9; 5; 384
-
- Modell
JG
- Repeated observation of yawning, clitoral
engorgement, and orgasm associated with
fluoxetine administration.
- J. Clin. Psychopharmacol
1989; 9: 63-65.
-
- Injured
temporomandibular joint associated with
fluoxetine-m onotherapy-induced repeated yawning
- Pae CU, JJ Kim et al Gen
Hosp Psychiatry 2003; 25; 3; 217-218
-
- Bâillements
et excitation sexuelle sous clomipramine. Place
des mécanismes serotoninergiques. A
propos of 2 cases
- Bertschy G Vandel S Sechter D Bizouard P
Encephale 1991; 17; 6;
515-7
-
- Sustained
yawning as a side effect of imipramine
- Goldberg RL Int J Psychiatry
Med 1983-84; 13; 4; 277-80
-
- Unusual
side effects of clomipramine associated with
yawning
- Harrison W, Stewart J, McGrath PJ, Quitkin F
Can J Psychiatry 1984; 29;
546
-
- Unusual side
effects of clomipramine associated with yawning
- McLean JD, Forsythe RG, Kapkin IA
Can J Psychiatry 1983; 28; 7;
569-70
-
- Hazard of
yawning
- Tesfaye Y, Lal S Canadian
Med Assoc J 1990; 142; 1; 15 1991;1 45;12;
1560
-
- Bâillements
: parfois un effet indésirable d'un
médicament
- Prescrire La Revue Prescrire
2005; 25 ; 265; 676
-
- Drug-induced
yawning:a review of the French pharmacovigilance
database
- Sommet A et al. Fundamental
Clin Pharmacol 2005; 19 (2):227 (abstract
P123).
-
- Serotonergic
modulation of yawning
- Urba-Holmgren R, Holmgren B, Rodriguez R,
Gonzalez RM Pharmacol. Biochem.
Behav1979; 11: 371-372.
-
- Observation
personnelle
-
- A case of
excessive yaawning with citalopram Pal S,
Padala PR.J Clin Psychiatry
2009;11(3):126
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