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Am J Med Sci. 2009 Jun;337(6):396-406. doi: 10.1097/MAJ.0b013e3181914a97.

An open-label controlled trial of theophylline for treatment of patients with hyposmia.

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Center for Molecular Nutrition and Sensory Disorders, The Taste and Smell Clinic, Washington, DC, USA.



To test the hypothesis that theophylline is effective in correcting smell loss in patients with hyposmia.


Three hundred twelve patients with smell loss (hyposmia) were evaluated to determine characteristics of their loss by psychophysical measurements of detection and recognition thresholds, magnitude estimation and hedonic values for 4 odors (pyridine, nitrobenzene, thiophene, and amyl acetate) by use of a forced-choice 3-stimuli staircase design previously documented in a double-blind study. Patients were then treated in a fixed design open-label clinical trial with oral theophylline. Drug was given in equal divided doses from 200 to 800 mg daily for 2- to 8-month periods and subjective and psychophysical measurements of smell function and blood theophylline levels were measured; results were compared with those obtained before treatment.


Subjective smell loss improved in 157 (50.3%) patients; smell function was considered normal by 34 (21.7%). Overall, 10.9% of patients in the study considered smell function returned to normal. However, measurements of mean detection and recognition thresholds improved significantly at each drug level; measurements of mean magnitude estimation and hedonic also improved. Improvement was greater at drug doses of 600 and 800 mg than at 200 or 400 mg. Once improvement occurred, as long as treatment was maintained, it persisted for as long as follow-up was measured.


Theophylline was effective in improving smell function in patients with smell loss. Improvement persisted as long as treatment was continued, which extended from 6 to 72 months.

[Indexed for MEDLINE]

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