A Case of Excessive Yawning With Citalopram

Sir: It has been identified but is not well-known or appreciated by practitioners that selective serotonin reuptake inhibitors (SSRIs) can cause excessive yawning as a side effect.

SSRIs are the treatment of choice for depression. The list of approved indications for these drugs has expanded to include obsessive-compulsive disorder, social anxiety disorder, generalized anxiety disorder, premenstrual dysphoric disorder, and eating disorders.

Gastrointestinal side effects, sexual dysfunction, and headache are the most common adverse effects seen with the use of these drugs. We report a case of a man who developed excessive yawning secondary to treatment with citalopram. A substantial amount of money was spent to treat his yawning before it was recognized that it could be a side effect of a medication.

Case report. Mr. A, a 58-year-old married white man with major depressive disorder, was admitted in December 2005 at the Comprehensive Epilepsy Center for electroencephalogram (EEG) monitoring to rule out epilepsy as a cause of excessive yawning. Mr. A's yawning spells had started several months previously and had become worse during the last couple of months. His estimated frequency of spells was 10 to 20 per day, with each spell lasting 10 to 30 minutes, and he would yawn 20 to 50 times per spell. Yawning spells would cause him to be lethargic, dizzy, and sometimes drowsy. These spells would come at any time and anywhere without warning. He found them distressing, embarrassing, and bothersome, so he decided to seek help from his primary physician, who did an initial evaluation and referred him to a neurologist to rule out a neurologic cause. Mr. A had had a transient ischemic attack a year before his December 2005 admission, from which he had fully recovered, and the neurologist recommended EEG, magnetic resonance imaging of the head with contrast, magnetic resonance angiography of the head, and Doppler studies of carotid arteries to rule out stroke, epilepsy, or tumor as a cause of excessive yawning. The results of all these studies were unremarkable. A cardiologist was also consulted to rule out a cardiac cause as the patient had a history of atrial fibrillation and 1 episode of chest pain. The cardiologist advised electrocardiogram, echocardiography, and angiography; these studies revealed no abnormality. Since this extensive workup could not point out the cause of the patient's excessive yawning, Mr. A was next referred to the epileptologist for EEG monitoring to rule out temporal lobe epilepsy.

Mr. A was admitted to the EEG monitoring suite for 5 days; continuous EEG monitoring and telemetry were performed, and prolactin levels were measured with each yawning spell. Electroencephalogram monitoring did not show epileptiform discharges, and prolactin levels stayed within normal range; telemetry showed sinus bradycardia ranging from 40 to 60 beats per minute with each spell. Complete blood cell count, comprehensive metabolic profile, international normalized ratio (INR), and urinary analysis results were also within normal range.

The medications he was taking at the time of admission were citalopram 20 mg/day for major depressive disorder, flecainide 50 mg every morning and 100 mg daily at bedtime for atrial fibrillation, and warfarin 5 mg/day. His depression was controlled well with citalopram, and atrial fibrillation was under control with flecainide. Mr. A denied using illicit drugs and admitted drinking socially.

On further questioning, the patient explained that his yawning began within 1 to 2 weeks of starting citalopram at 10 mg a day. It was not bothersome to him until 2 months previously when the dose of citalopram was increased to 20 mg/day for uncontrolled depression. His depression had responded well to the increased dose of citalopram, and he denied any daytime drowsiness.

During this hospitalization, epilepsy was ruled out, and extensive neurologic and cardiac workup ruled out other neurologic and cardiac causes of excessive yawning; normal test results for electrolytes, liver panel, and renal panel ruled out liver or renal disease.

SSRIs can rarely cause excessive yawning; thus, at the time of discharge from the hospital, we advised the patient to taper off citalopram gradually and to begin treatment with a non-SSRI antidepressant under the supervision of a psychiatrist.

After discharge, Mr. A tapered himself off citalopram treatment slowly over 2 weeks. With the weaning off of the dose of citalopram, his excessive yawning diminished and eventually stopped as citalopram was discontinued. Upon follow-up after 1 month of discontinuation of citalopram, Mr. A reported being free of excessive yawning. On further follow-up after 2 months, he continued to be free of excessive yawning, but his depression had relapsed. We followed up with the patient on the telephone 2 years after initial contact. He continued to be free from excessive yawning. He denied any depression at that time and had not taken any antidepressant in the interim.

Various causes of excessive yawning are presented in Table 1. In this case, the patient's excessive yawning occurred with the introduction of citalopram 10 mg/day but it was not bothersome to him until citalopram was increased to 20 mg/day; his excessive yawning remitted following discontinuation of citalopram.

Table 1.

Causes of Excessive Yawning

Epilepsy

Encephalitis

Brain tumors, stroke

Multiple sclerosis

Progressive supranuclear palsy

Opiate withdrawal

Heart attack, aortic dissection

Liver failure, renal failure

Drugs: selective serotonin reuptake inhibitors, clomipramine, desipramine, antiparkinsonism drugs

Beale and Murphree¹ report 2 cases of excessive yawning with SSRIs. In the first, a patient was started on treatment with fluoxetine 10 mg/day for major depression, developed excessive yawning following 1 to 2 weeks of therapy, and remitted on discontinuation of fluoxetine; excessive yawning resumed following citalopram 10 mg/day initiation and stopped on discontinuation of citalopram. In the second case, a patient who was started on treatment with 50 mg/day sertraline for major depressive disorder also developed excessive yawning within 1 to 2 weeks after initiation of therapy, and his yawning remitted within 1 week of discontinuation of sertraline. In both cases, bupropion was started, and excessive yawning did not recur with bupropion therapy.

In a 6-week placebo-controlled trial using citalopram (N = 1,063) and placebo (N = 446), 2% of participants in the citalopram arm developed yawning, compared to < 1% of patients taking placebo.⁴ In another study, 7% of patients with obsessive-compulsive disorder, 11% of patient with bulimia, and 1% of patients with panic disorder receiving fluoxetine reported yawning as a side effect of treatment, compared with 0% of patients receiving placebo.⁴ In a study by McLean et al.,² clomipramine-induced yawning in humans was reported. In another study by Mogilnicka et al.,³ yawning in rats treated with desipramine was documented. According to Goessler et al.,⁵ the hypothalamus and hippocampus in the brain play an important role in yawning. Research has shown that yawning is largely affected by dopamine. Some other neurotransmitters involved are nitric oxide, serotonin, norepinephrine, acetylcholine, glutamate, γ-aminobutyric acid, oxytocin, and other neuropeptides; these have been shown to increase yawning when injected into the hypothalamus of animals.⁵

This case demonstrates that SSRIs can be associated with a bothersome side effect of excessive yawning, and this has been described in the literature with different SSRIs in varying incidences. If practitioners recognize this association, expensive and extensive workups may be prevented.

Sarita Pal, M.D.
Creighton University Medical Center, University of Nebraska Medical Center
Prasad R. Padala, M.D.
Department of Psychiatry, University of Nebraska Medical Center, U.S. Department of Veterans Affairs Medical Center, Omaha, Nebraska