The Effect of Oral Theophylline on Traumatic Anosmia: A Prospective, Randomized Clinical Trial

Theophylline has been theorized to promote neural olfactory signaling and sensory axonal regeneration. In this study, our objective was to investigate the effect of oral theophylline on the treatment of traumatic anosmia.

We enrolled patients who had complained of traumatic complete anosmia. Eligible patients were randomly assigned to 2 groups. In the theophylline group, oral theophylline (400 mg bid) was prescribed for 6 months and patients also underwent olfactory training (OT). In the OT group, patients performed OT only for 6 months. The bilateral and unilateral olfactory function was evaluated using the phenyl ethyl alcohol (PEA) odor detection threshold test and the traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC), before and after treatment.

A total of 41 patients in the theophylline group and 41 in the OT group completed the study. Before treatment, the PEA threshold for all patients was -1. After 6 months of treatment, the unilateral right PEA threshold improved significantly in patients taking theophylline for 6 months (P = .018), but did not change significantly in patients who only performed OT (P = .317), and was significantly better in patients taking theophylline for 6 months than in those who only performed OT (P = .027). However, UPSIT-TC scores did not improve significantly in either the theophylline or OT group.

The combination therapy of oral theophylline with OT could have a better effect on traumatic anosmia than OT alone.