Paroxetine‐induced excessive yawning (2006)

Paroxetine is a selective serotonin re-uptake inhibitor. Because of its prevalence, its clinical features (such as efficacy, side-effects and withdrawal symptoms) are well-known to clinicians. However, more subtle side-effects might not become evident. In regard to this, this paper reports two cases of excessive yawning as side-effects of paroxetine. Although to date there have been case reports of excessive yawning induced by other types of selective serotonin re-uptake inhibitors (fluoxetine,1–3 citalopram,3 sertraline3), to the author's knowledge this is the first report of paroxetine-induced excessive yawning. The patient was a 21-year-old Japanese woman who began treatment for symptoms of panic disorder with 10 mg paroxetine orally after every evening meal. The next day the patient began to yawn excessively in the daytime without feeling drowsy despite adequate sleep at night. She also had difficulty when intentionally stopping herself from yawning. Frequency of yawning was greater in the morning than in the afternoon. Then, 4 weeks after starting the treatment, the dose of paroxetine was decreased to 5 mg. Consequently, the frequency of yawning decreased by approximately half, but excessive daytime yawning still continued. Six weeks after starting the treatment, her symptoms disappeared, so the treatment with paroxetine was ended. As a result her excessive yawning was resolved completely. The patient was a 43-year-old Japanese woman with symptoms of panic disorder. Treatment with 10 mg paroxetine orally after every evening meal was started. Two weeks later, the dose of paroxetine was increased to 20 mg. The day after paroxetine was increased, excessive daytime yawning occurred. The yawning was not associated with sedation. The patient could not endure yawning voluntarily. In this case, frequency of yawning was greater in the morning and gradually decreased in the afternoon. Seven days after paroxetine was increased, because her symptoms improved, the dose of paroxetine was decreased to 10 mg again. Consequently, her excessive yawning disappeared completely. Although yawning is a phylogenetically old, stereotyped event and a common physiological event in humans and animals, the exact neuropharmacological mechanism of yawning induction has yet to be clarified because various types of neurotransmitters and neuropeptides interact in a complicated way.4 In these cases, however, acute increases in central serotonergic neuronal activity caused by paroxetine might be involved in the phenomenon. In particular, it is possible that failure of serotonergic modulation of yawning5 could be caused by excessive stimulation of the 5-HT2C receptor4 induced by paroxetine in the synapses in the brain area involved in control of yawning (i.e. paraventricular nucleus, hippocampus, pons and/or medulla oblongata4). Concerning the clinical features of paroxetine-induced excessive yawning, it is suggested that it is dose dependent, and that it decreases with time course, that is, it seems to be dependent on the concentration in the blood. In addition, it appears not to be associated with sedation or drowsiness, and it seems that not only the frequency of yawning but also the intensity of yawning are outstanding. In conclusion, clinicians should be aware that selective serotonin re-uptake inhibitors such as paroxetine could evoke excessive daytime yawning as a side-effect.