As we become more experienced with the
long-term use of selective serotonin reuptake
inhibitors (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. We present two cases in which excessive
daylime yawning was associated with SSRI
treatment.
Case 1 : Mr S. is a 32-yr-old
computer analyst who began treatment for a major
depressive episode with 10 mg/d fluoxetine. His
depression responded rapidly to treatment,
however following 1-2 wk therapy, he began to
experience excessive daytime yawning. The
patient estimated that yawning occurred 20-30
times daily. The yawning was not associated with
sedation or a feeling of needing sleep. He was
disturbed by this effect, as yawning occurred
during business meetings 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. Because of inhibition of ejaculation,
fluoxetine was discontinued after 9 months. At
the patient's request, no medications were given
during the following 3 months and yawning
quickly diminished to 3-4 times per day. The
subject's depression recurred however, and 10
mg/d citalopram was prescribed. Excessive
yawning resumed 1-2 wk following citalopram
initiation at a frequency of 20-30 times per
day. Again, adverse sexual effects occurred and
citalopram was discontinued. Treatment with 100
mg/d bupropion SR was begun and the excessive
yawning bas not recurred.
Case 2 : Dr L. is a 46-yr-old
physician who began treatment of a major
depressive episode with 50 mg/d sertraline.
Following 1-2 wk treatment, he began to
experience 75-100 yawning episodes daily. This
was very distressing to him, as the yawning
occurred in the presence of patients, coworkers
and during meetings. Frequently, patients made
comments regarding the physician's yawning. This
was so bothersome to him that discontinuation of
the sertraline was necessary. The excessive
yawning remitted within 1 wk and bas not
recurred following 18 months of treatment with
150 mg/d bupropion SR.
Discussion : In the cases presented,
yawning occurred with three different SSRI
agents and remitted following SSRI
discontinuation. In one case, the excessive
yawning returned upon re-challenge with a
different SSRI and remitted again following its
discontinuation. Neither patient experienced
this side-effect with bupropion therapy. The
yawning did not seem to be associated with
daytime sleepiness or sedation and was
moderately to severely bothersome to both
patients. In preliminary studies, up to 11 % of
patients receiving fluoxetine reported yawning
as a side-effect of treatment, compared with 0%
taking placebo [Physicians Desk Reference
(PDR), 1999a]. This appeared to be more
common in patients with bulimia and
obsessivecompulsive disorders than in depression
(PDR, 1999a). In fact, no patients in early
studies of fluoxetine in depression reported
yawning as a side-effect (PDR, 1999a). Initial
studies of citaloprarn demonstrated only 2% of
patients reporting yawning as a side-effect
compared to < 1 % on placebo (PDR, 1999c).
Yawning was not assessed in placebo-confrolled
trials of sertraline use (PDR, 1999b).
Excessive yawning has been reported in
humans taking clomipramine (McLean et al., 1983)
and in rats treated with desiprarnine (Mogilnica
et al., 1986). In the desipramine-treated rats,
yawning was reduced with haloperidol
administration leading the authors to postulate
that a dopaminergic mechanisrn may be involved.
They also theorized that noradrenergic
stimulation (through antidepressant treatment)
may play a role in yawning induction. Serotonin
reuptake inhibitor administration did not lead
to increased yawning in rats. In our cases
however, a serotonergic mechanism may have
played a role. Complex neurotransmiter systems
make pin-pointing an exact mechanisrn of yawning
induction difficult and conflicting data exist
regarding the role of specific
neurotransmitters. In the two cases presented
here, yawning seemed to bc particularly frequent
and bothersome. Although activation can be
commonly experienced by some patients receiving
SSRIs, others report daytime sleepiness as a
side-effect. In both of our subjects, insomnia
or sleep difficulty was not associaled with the
excessive yawning nor was a sense of daytime
sedation oi sleepiness
Although the mechanisms of the excessive
yawning remain unclear, il seems to be related
to something other than simple fatigue
associated with depression, insonmia, or
sedation associaled with SSRI therapy. We look
forward to future reports of this interesting
side-effect in association with psychotropic
agents.
