mise à jour du
1 février 2009
Progress in Neuro-Psychopharmacology & Biological Psychiatry
Venlafaxine-induced excessive yawning
Chen-Hsin Chen, Mong-Liang Lu
Department of Psychiatry, Wan Fang Hospital & School of Medicine, Taipei Medical University, Taipei, Taiwan
Bâillements et dépression - Yawning and depression
Le bâillement: de la physiologie à la iatrogénie
Yawning: from physiology to iatrogenic effect


-Nayak R, Bhogale GS, Patil NM Venlafaxine and excessive yawning: is there any link? J Neuropsychiatry Clin Neurosci. 2011 Spring;23(2):E56-7.


Yawning is a complex stereotyped behavior with unknown physiological functions. Excessive yawning without a decrease of the arousal level has been noted with various drugs (Sommet et al., 2007). Almost all these treatments have a central nervous system action.
Venlafaxine, a selective serotonin and norepinephrine reuptake inhibitor (SNRI), is prescribed for the treatment of major depression and anxiety disorders. Although yawning was an uncommon side effect of venlafaxine during the premarketing and postmarketing clinical trials, no cases of severe and disabling yawning have been reported till now.
Case report
Mr. A was a 24-year-old man, with no previous history of medical or psychiatric disorders. He suffered from dysphoric mood, loss of interest, difficulty in concentration, and suicidal ideation for eight weeks and was diagnosed with a first episode of major depressive disorder.
The results of his physical and neurological examinations were normal. Prior to the start of antidepressant treatment, he was psychotropic drug naïve. During antidepressant treatment, he did not take any concurrent drugs or herbal medication.
He began to receive 75 mg/day of venlafaxine extended release (XR) for major depressive disorder. After four weeks of 75 mg/day of venlafaxine XR, the dose of venlafaxine XR was increased to 150 mg/day due to inadequate response. His depressive symptoms significantly improved after two weeks of receiving venlafaxine XR at 150 mg/day.
But he experienced excessive yawning seven days following the increment of the venlafaxine dose. The yawning was not associated with drowsiness, yet he was unable to intentionally stop himself from yawning. He had more than 50 occurrences of yawning daily, frequently in the morning.
He was disturbed by this effect, as the yawning occurred during his daily activities and interpersonal interactions. The patient worried that others would interpret the yawning as a sign of indifference or boredom.
At the patient's request, the dose of venlafaxine XR was reduced to 75 mg/day and yawning completely disappeared within three days thereafter. His depressive symptoms did not recur.
Yawning is under the control of several neurotransmitters and neuropeptides which interact in a complicated way (Daquin et al., 2001). Among these substances, the well known are dopamine, serotonin, noradrenaline, acetylcholine, excitatory amino acid, nitric oxide, adrenocorticotropic hormone-related peptides and oxytocin (Melis and Argiolas 1997; Argiolas and Melis 1998).
Abnormal yawning is present in numerous pathologies (neurological, psychiatric, infectious, and iatrogenic disease) (Daquin et al., 2001). In our case, a close temporal relationshipwas noted between the onset of the excessive yawning and the increased dose of venlafaxine, as well as its remission and the decrement of the medication. A dose-dependent side effect of venlafaxine is the mostly likely cause of excessive yawing in this patient.
In preliminary studies, up to 3% of patients receiving venlafaxine reported yawning as a dose-dependent side effect of treatment (package insert of Effexor™). Depending upon the dose, venlafaxine has different degrees of reuptake inhibition of serotonin (most potent at low dose), noradrenaline (moderate potency and present at higher doses), and dopamine (least potent and present at highest doses) (Muth et al., 1991; Weikop et al., 2004).
In our case, the excessive yawning disappeared with the reduction of the venlafaxine dose. This might suggest that the noradrenergic and dopaminergic mechanisms may play a role in the relationship between yawning and venlafaxine dosage. Antidepressants, in particular serotonin reuptake inhibitors, are drugs that have been implicated in yawning.
However, there is very little research on this, because for most people receiving antidepressants, yawning is not a serious problem. To date, there are only a few case reports of excessive yawning induced by serotonin reuptake inhibitor antidepressants (Beale and Murphree 2000; Harada 2006; De Las Cuevas and Sanz 2007; Gutierrez-Alvarez 2007; Sommet et al., 2007) and SNRI duloxetine (De Las Cuevas and Sanz 2007). Pae et al. (2003) presented an extreme case report of an injured temporomandibular joint associated with fluoxetine-induced repeated yawning.
Therefore, the frequency and intensity of antidepressant-induced yawning in some patients could be disturbing and disabling.
In conclusion, although the mechanism of excessive yawning is not clear, clinicians should notice that venlafaxine could evoke such a disabling side effect. As in the present case report, the side effect was dose-dependent and was relieved by decreasing the dose.
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-Nayak R, Bhogale GS, Patil NM. Venlafaxine and excessive yawning: is there any link? J Neuropsychiatry Clin Neurosci. 2011 Spring;23(2):E56-7.