Yawning often occurs during states of
increased sleep propensity. Depression is
associated with sleep problems and tiredness.
The aim of this paper is to review the present
knowledge about possible changes of yawning
during an episode of major depression (MD) and
to report data on yawning from an online
depression forum comprising of 450 000 postings.
A literature search did not reveal any study
about yawning in people with MD when compared to
controls. However, there is evidence for an
increased frequency of yawning under the
influence of antidepressants. Analysis of the
depression forum postings revealed 63 people
writing about increased yawning in the context
of depression. However, all but one of them were
treated with antidepressants; and yawning was
not reported as a symptom of depression, but in
most cases (N=56) as occurring as a result of
treatment with antidepressants. These findings
are in agreement with a tonic hyperarousal in
typical depression which is reduced by all
standard antidepressants. For clinicians, it
would be of interest to know whether yawning is
reduced in untreated depression and whether it
predicts treatment outcome.
Macaques
Exhibit a Naturally-Occurring Depression Similar
to Humans
Introduction
Yawning is an involuntary behavior, common
in many species [1]. Several
explanations for spontaneous yawning have been
suggested, but debate about biological functions
continues [1]. In line with subjective
experience, electroencephalography (EEG) and
behavioral studies provide convincing evidence
that yawning preferentially occurs during states
of increased sleepiness [2, 3].
Typical Depression: Exhaustion Rather
than Sleepiness
Tiredness and feelings of fatigue or
weariness are typically reported in MD. However,
whether unmedicated patients with MD experience
more yawning than healthy controls is unknown
(see below). In contrast, personal experience
with patients suffering from MD even suggests a
reduction of yawning in MD; a speculative
hypothesis which awaits further investigation in
future studies. This points to the problem that
terms, such as tiredness and fatigue, are used
for 2 completely different states: (i)
tiredness/fatigue in the sense of sleepiness, i.
e., increased tendency to get drowsy or fall
asleep and (ii) tiredness/fatigue in the sense
of exhaustion with a tonically high inner
tension and physiological arousal [4].
It is the latter syndrome which is typically
found in patients with unipolar depression.
These patients have long sleep onset latencies
[5&endash;7], difficulties relaxing and
often show signs of higher noradrenergic and
hypothalamicpituitary- adrenal activity [8,
9]. Tonically high EEG-assessed CNS-arousal
is a replicated finding in unmedicated patients
with MD [10&endash;12]. According to the
recently proposed vigilance regulation model of
affective disorders, the withdrawal and
sensation avoidance in depression is interpreted
as an autoregulatory reaction to this tonically
increased CNS arousal [13].
Review on Yawning in Depression: Only
Reported under Antidepressants
A Pubmed Medline search entering yawning and
depression as search terms, complemented by a
search of the respective reference lists, was
performed. No studies comparing yawning in
unmedicated patients to that in healthy controls
were identified. Concerning associations with
depression scores in normal populations, one
small, unpublished study [14] (N = 31)
associated scores from a yawning questionnaire
with a self-rated depression scale in a sample
of friends and colleagues. However, as this
study did not control for major confounders such
as age, sex, pathological sleepiness and drugs,
these findings remain somewhat ambiguous. For
example, as in this particular study age was
negatively correlated with yawning and with
depression, the reported positive association
between yawning and depression might be
artificial. Furthermore, as will be discussed
below, antidepressants can cause yawning, which
could have resulted in an artificial positive
correlation between yawning and depression.
The only studies the Medline search
identified were those on depressed patients
treated with antidepressants. These were several
case reports [15&endash;29] and 2
clinical trials [30, 31], in which
yawning was reported as a side effect of
antidepressants. Concerning the clinical trials,
yawning was assessed by means of side effect
scales, not to assess the frequency of
spontaneously occurring yawning. Therefore, it
is not surprising that the vast majority of
patients did not report any yawning before or
during treatment. Nonetheless, these clinical
studies give evidence for increased occurrence
of yawning under antidepressants, especially the
study by Nierenberg et al. [30] which
included a placebo control and found that while
no patient under placebo reported yawning, 6
patients reported yawning under escitalopram
(2.2 %) and 15 (5.5 %) under duloxetine
[30]. The same picture emerges in the
randomized clinical trials, which are reviewed
in the Physicians' Desk Reference [32]
and which assessed yawning as side effect: Under
paroxetine 4&endash;5 % of patients with MD
reported yawning, whereas 0 % under placebo
[32 (p. 1495, 1507, 2424) ]. Depending
on dose, yawning was also reported in 1&endash;4
% of patients with MD taking desvenlafaxine
compared to < 1 % under placebo [32 (p.
3413) ]. The case reports also suggested
yawning as a side effect of antidepressants,
which occurred a few days to weeks after
treatment initiation and disappeared after dose
reduction or withdrawal. In detail, yawning has
been associated with fluoxetine [15, 19,
26&endash;28], paroxetine [16, 23,
28], sertraline [15, 28], (es)
citalopram [15, 22, 29], duloxetine
[20], venlafaxine [18],
Hypericum perforatum [16], imipramine
[21] and clomipramine [16, 17,
25]. As experimental studies suggest a role
of different neurotransmitters in yawning,
including serotonin and dopamine [33],
this side effect may be caused by modulation of
monoaminergic transmitter systems. Most case
reports did not report an association between
yawning and drowsiness. However, drowsiness or
sleepiness was not systematically assessed.
Thus, the increased yawning might additionally
also reflect the drug-induced decrease of
arousal.
Sleepiness as Side Effect of
Antidepressants
Drowsiness and somnolence are known frequent
side effects of all common antidepressants
[34&endash;37]. Indeed, most
antidepressants, including those which are
commonly labeled as "activating" drugs, reduce
the firing rate of neurons in the noradrenergic
locus coeruleus (LC), with LC activity playing a
pivotal role in arousal. Preclinical studies
found this reduction for acute and for 2-week
applications, applying different serotonin-,
norepinephrine-, serotonin-norepinephrine and
norepinephrine-dopamine reuptake inhibitors,
tricyclic antidepressants and MAO inhibitors
[38]. As also electroconvulsive therapy
reduces the firing rate of neurons in the LC, it
was suggested that this reduction might be a
common pathway of antidepressant action
[39]. According to the vigilance
regulation model of affective disorders
[13], this effect could normalize the
tonically high CNS arousal found in patients
with MD.
Reports of Yawning in an Online
Depression Forum
As a first step to obtain more information
about yawning in depression, we analyzed all
postings of users of an online discussion forum
(www.diskussionsforum-depression.de) for
depressed patients, in which yawning was
mentioned. The database of the online forum
contains about 450 000 postings written by 24
000 people during the last 11 years. This
database was searched for the keyword "gähn
* " ( = "yawn * ") using the php- MyAdmin tool
(http://www.phpmyadmin.net/). The resulting
selection of 373 postings was then examined
individually in order to remove mentions of
yawning that were only metaphorical, duplicates
within one post, or not related to the posters
themselves (such as "copy-paste" citations of
other posts). This resulted in 66 people writing
about yawning and comprising 120 postings (0.027
% of the content). 63 subjects reported
increased yawning, where all but one were
treated with antidepressants. The only subject
who reported yawning without drug treatment was
a woman with "anxiety, burnout and depression"
in a posting about "lack of energy". Most of the
treated subjects (56 of 62) reported their
yawning to occur during antidepressant
treatment. Notably, from the remaining 6
participants who did not attribute yawning to
drug therapy but rather to their depressive
symptomatology, 5 reported symptoms, which
suggest atypical depression, a condition
associated with sleepiness and hypoarousal
rather than hyperarousal [see 13]. These
5 patients reported symptoms which seem to fit
well the diagnostic features of atypical
depression: hypersomnia ("permanently yawning,
dead tired, can only go to bed and then fall
asleep immediately", "I need about 9&endash;10 h
of sleep… I have no problems sleeping so
long…only concerned about [daytime]
tiredness and exhaustion… no energy…
yawning due to lack of energy…"),
hyperphagia ("eating from 5&endash;7 bars of
chocolate… sugar addiction [patient
reported no further chocolate consumption since
mood had improved]") and leaden paralysis
("tired legs", "body feels paralyzed, like a
stone"). Only 3 subjects reported a reduction of
yawning which was accompanied with increased
wakefulness; 2 of the subjects during acute
withdrawal of antidepressants, and the third
when starting with sulpiride treatment. Of the
subjects reporting yawning 71 % took a SSRI and
19 % a SNRI. For further examination, 12
participants were excluded who took more than
one psychotropic drug or who did not specify
their medication. The remaining 51 patients, who
reported yawning during monotherapy, comprised
29 patients taking citalopram or escitalopram
(57 %), currently the most often prescribed
antidepressant in Germany [40]. The
other compounds were venlafaxine (8 patients),
sertraline (5 patients), fluoxetine (3
patients), fluvoxamine, duloxetine and
mirtazapine (each with 2 reports). With
exception of the latter, for all the mentioned
SSRI and SNRI yawning is reported as frequent
side effect in the package inserts. From the 51
persons under monotherapy, 21 quantified their
yawning as permanently, 5 as frequently; and
most of the subjects described yawning as an
adverse reaction starting during the first weeks
of medication.
Conclusion
In conclusion, yawning was hardly ever
reported by unmedicated participants of an
online depression forum. This is in line with
the assumption of a tonic hyperarousal in
typical unipolar depression [13]. In
contrast, yawning was spontaneously reported and
recognized as an adverse reaction by the forum's
patients taking antidepressants. Clinicians
should be aware of this possible side effect of
antidepressants and that it might reflect the
desired effect of arousal-reduction in treatment
of MD. It is a limitation that yawning
variability was not systematically assessed in
the online forum. One can assume that only
clearly increased and bothersome yawning will
spontaneously be reported in an online forum.
Therefore, a possible reduction in yawning and
also a tolerable increase might only be detected
in studies systematically assessing yawning in
MD and matched controls. Whether yawning could
be used clinically for the (differential)
diagnosis of depression or for the prediction of
treatment outcome to antidepressants remains
also to be addressed in future clinical studies.
maceuticals, Servier and Otsuka Pharma; a
consultant for Nycomed; and a speaker for
