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20 janvier 2002
International J Psychitary in medecine 1984;13(4):1983-1984
Sustained yawning as a side effect of imipramine
Richard L Goldberg Deptament of psychiatry
Georgetown University Hospital
Bâillements et dépression - Yawning and depression
Le bâillement: de la physiologie à la iatrogénie
Yawning: from physiology to iatrogenic effect
The antidepressant imipramine is a dibenzazepine tricyclic antidepressant. Its mechanisms of action include blocking the reuptake of both norepinephrine and serotonin at the synaptic cleft within the CNS. Imipramine also possesses anticholinergie properties and seems to have little effect upon dopaminergic systems within the CNS.

Many side effects from imipramine are knwn and listed in the 1982 Physician'sDeskReference(PDR). However, search of this reference and the index Médicus" did not reveal any reports of spontaneous and sustained periods of yawning, uncoupled from sedation, and secondary to imipramine administrat ion. In this report, the case of a woman who had such periods of yawning after the traetment of depression with imipramine is presented.


Ms.A was a thirty-year-old unmarried woman who sought psychiatric help because of the onset of a major depressive episode. Her depression began three months prior to consultation and was precipitated by career changes and the loss of her boyfriend. Ms. A described feeling sad, hopeless, and helpless. She reported that her depression was worse in the morning and was accompanied by decreased appetite, several pounds of weight loss, terminal insomnia, decreased attentiveness, fatigue and tearfulness. She denied any suicidal ideation, hypomanic or manie episodes, medical illnesses, or drug or alcohol abuse. The patient had no prior psychiatric illness, although an older brother had committed suicide ten years earlier, and her father was an alcohol abuser. Ms. A's physical and laboratory examinations were normal. Dexamethasone suppression test was not performed.

Because of Ms. A's major depressive episode, she was treated with a regimen of imipramine, 50 mg b.i.d. This initial dosage was increased over two weeks to imipramine, 150 mg b.i.d. At this dosage level, Ms. A's imipramine blood level was 170 ng/ml (therapeutic range l~0-300 ng/ml), and she experienced a dramatic alleviation of her depression. She tolerated the medication well and only complained initially about dryness of her mouth, slightly blurred vision and constipation. After three weeks treatment with imipramine, 150 mg b.i.d., Ms. A reported the occurrence of unusually long episodes of yawning which she retrospectively observed frorn treatment onset but which had worsened as her dosage of imipramine was increased, The yawning periods would begin spontaneously and last from five to fîfteen minutes about twice per day. Ms. A denied any signs of fatigue or sedation during these periods. Just as' spontaneously as her yawning would begin it would end, leaving Ms. A with a feeling of embarrassment, especially if others were present. On one occasion, her yawning was observed in a treatment session and did not appear related to somnolence or boredom. Ms. A had improved clinically; her medication dosage was gradually decreased to imipramifie, 150 mg q.d. for four months, and then eventually discontimied. As the médidation dosage was decreased, the periods of sustained.yawning occurred less frequently (about once per day). Yawning ended two days after the medicâtion was terminated.


Yawning is a multiple motor act with many causes and with an obscure mechanism in humans. Borodom, anxiety, and sleepiness can all cause yawning. Yawning can also occur in the presence of intracranial disease and in the absence of the above-mentioned states. For example, Ms. A experienced periods of yawing uncoupled from any sedative side effects of imipramine.

In neuropharmacological studies with rats and cats, yawning is a behavioral response to drug challenges which is carefully documented. Yawning in. rats is facilitated by drugs which stimulate dopaminergic or cholinergie activity within the CNS, while in cats yawning is inhibited by dopamine transmission, but facilitate by serotonin activation. One case of yawning as a drug induced effect to medication in humans bas been reported. The patient was a young man suffering from postanoxic action myoclonus who received sodium valproate as treatment. Shortly after drug initiation, the patient developed yawning every two to three minutes which appeared to be dose related to sodium valproate. On the basis of familiarity with the literature on yawning in rats it was assumed that the yawning in this case was caused by doparninergic activation secondary to sodium valproate treatment. Pimozide, a potent dopamine antagonist, was administered and yawning abated.

The case of Ms. A is the first report of yawning, uncoupled from sedation, as a side effect of imipramine. The correlations between initiation of imipramine treatment and the onset of yawning, as well as between the reduction of yawning with dosage decrease, suggest that irnipramine was the cause of yawning. Unfortunately, data concerning yawning and drug rechallenge are not available.

Since imiprarnine has little effect upon dopamine activation, another mechanism may be responsible for the occurrence of yawning. Perhaps serotonin, which causes yawning in cats and whose reuptake is inhibited by imipramine, may also play a role in yawning in humans. The case of the young man treated with sodium valproate for postanoxic action myoclonus can lend some credence to this hypothesis despite successful remission of yawning with pimozide administration. The underlying mechanism for postanoxic myoclonus is serotonergic deficiency. In the case cited above, sodium valproate might have acted upon serotonergic systems and restored serotonin levels which subsequently improved postanoxic action myoclonus and. caused yawning. Suffice it to say that neither the rat nor cat models for yawning maybe totally applicable for humans.

If yawning is a side effect to imipramine, it can go unreported by patients and yet be troublesome enough for the patient to inhibit medication compliance. Especially when noncompliance is suspected by the clinician, inquiry into the presence of sustained yawning should be made.If a patient experiences this side effect, he should be informed that it is reveriible. When sustained yawing occurs, its severity seems dose related and can be managed by dose reduction if that is not clinically contraindicated. In other instances, switching antidepressant medication to one which is less serotonergic than imipramine may eliminate this problem and still provide alleviafion of depression..