Zolpidem Tartrate Use as Contributory Factor in Sinus Disease (2006)

849 DEAR EDITOR, WE WRITE TO SHARE OUR EXPERIENCE WITH A PATIENT WHO EXHIBITED SYMPTOMS OF CHRONIC RHINOSINUSITIS DUE TO ZOLPIDEM TARTRATE USE. THIS patient’s nasal congestion, sinus pressure, and headache resolved with the discontinuation of zolpidem tartrate. Our MEDLINE search coupling the terms zolpidem tartrate and Ambien with sinusitis, rhinitis, rhinosinusitis, nasal congestion, rhinorrhea, allergy and otolaryngology revealed no published association. However, inquiry to Sanofi-Aventis revealed that cases of sinus complaints in association with zolpidem tartrate use have been reported. In this instance, a 55-year-old female nonsmoker was unsuccessfully treated for 12 years for symptoms of chronic rhinosinusitis. Her past medical history revealed asthma, mitral valve prolapse, multinodular goiter, osteoporosis, gastroesophageal reflux disease, and insomnia. She originally described symptoms of nasal congestion, sinus pressure, and headache and complained of recurrent sinus infections characterized by increased facial pain, mucopurulent discharge, postnasal drip, cough, and low-grade fevers with malaise. Skin testing was positive only to hormodendrum, and immunologic work-up was negative. Initial medical therapy with nasal decongestants, allergy medications, and courses of antibiotics failed to resolve her symptoms. She underwent functional endoscopic sinus surgery, septoplasty, and bilateral partial inferior turbinectomy in 1993. Despite an initial improvement, her nasal congestion and headaches soon returned. Endoscopic examinations demonstrated well-healed postoperative paranasal sinus cavities. Computed tomography scans showed normal postoperative changes in the paranasal sinuses. Her symptoms persisted despite medical therapy by neurology, allergy, and pulmonary consultants for presumed contributing factors of migraines and allergic rhinitis. The patient’s symptoms completely resolved upon discontinuing her long-term zolpidem tartrate (Ambien) therapy for insomnia. She has been symptom free and off all rhinosinusitis and headache medications for 9 months. Zolpidem tartrate is a nonbenzodiazepine, nonbarbiturate hypnosedative that is “the #1 prescribed sleep aid in America,” having largely replaced the benzodiazepine class as pharmacologic therapy for insomnia and related disorders. 1 Zolpidem was first introduced in France in 1992 under the trade name Stilnox, followed by marketing in the United States as Ambien. Hypnosedative drugs act on the g-aminobutyric acid (GABA) receptor complex to produce their sedative effects. The classic benzodiazepine drugs act nonselectively on both the ω 1 and ω 2 GABA A receptorbinding sites, producing both sedation and memory/cognition effects, respectively. Zolpidem acts selectively on the ω 1 receptor of the GABA A molecule, thereby producing sedation similar to that of the benzodiazepines but without the side effects of memory impairment. 2,3 It is quickly absorbed and distributed, reaches peak plasma levels in 1.5 hours, and has a short half-life of 1 to 2.4 hours. 2 Thus, it works rapidly to induce and maintain sleep but has few after-effects of daytime somnolence after a full 7 to 8 hours of sleep. Side effects and adverse reactions with the use of zolpidem are reported to occur in 1% to 30% of patients. The most common adverse reactions are central nervous system-related, with headache as the dominant complaint (19% to 28.4%), followed by drowsiness (8% to 16.6%). 2-6 Other adverse effects include dizziness, vertigo, dry mouth and bitter or metallic taste, nausea, emesis, dyspepsia, diarrhea, myalgias, and arthralgias. Various psychiatric complaints of anxiety, confusion, depression, nightmares, and hallucinations have been reported. 2-6 In our review of the published literature, we found no report of any rhinologic side effects of zolpidem; a related nonbenzodiazepine hypnosedative, zaleplon, is reported in the pharmacology literature as infrequently causing rhinitis and pharyngitis symptoms. 2 However, the manufacturing company of zolpidem, Sanofi-Aventis, reports that symptoms of rhinosinusitis can occur in patients treated with zolpidem. According to the detailed drug information available on their web site, the incidence of rhinosinusitis in patients on zolpidem is 4%, compared with 2% in the placebo group. Rhinitis is reported in 1% (placebo 3%), upper respiratory infection symptoms in 5% (placebo 6%), and pharyngitis symptoms in 3% (placebo 1%). 4 A mechanism of action for zolpidem and related sedative-hypnotics to produce these sinonasal complaints has not yet been described. Bateman and Woolford reviewed multiple drug classes for their rhinologic side effects and noted that one drug of the hypnotic class, chlomethiazole, may cause rhinitis. Other central nervous system medications are noted to produce sinonasal complaints due to the widespread effect of these drugs on the various neurotransmitter systems of the central nervous system, including those of the autonomic nervous system. The α- and β-blocking properties of many of these drugs interfere with the normal sympathetic tone of the sinonasal mucosa. The drugs cause vasodilation and mucosal engorgement, producing symptoms of congestion and rhinorrhea. This theory has not, however, been applied to the hypnosedative class, nor to other psychiatric drug classes known to produce sinonasal complaints, such as the selective serotonin-specific reuptake inhibitors, antiepileptics, and anti-Parkinson drugs. 7