xRead - Olfactory Disorders (September 2023)

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INTERNATIONAL CONSENSUS ON OLFACTION

TABLE IX.36 Use of minocycline to treat OD Study Year LOE Study design

Study groups

Clinical end point Conclusions

Reden Minocycline in the given dosage has little or no effect on the recovery of human OF following postinfectious olfactory loss; however, spontaneous recovery is found in ≈ 20%of the patients over an observation period of 7 months LOE = level of evidence; OD = olfactory dysfunction; OF = olfactory function; PIOD = postinfectious olfactory dysfunction; SS-TDI = threshold, discrimination, and identification. et al 1584 2011 1b Randomized, prospective, double-blind, placebo controlled Patients with PIOD (n = 55) receiving either minocycline (2 × 50 mg/day) or placebo for 3weeks Improvement in SS-TDI

Minocycline was first evaluated as a neuroprotective agent in an animal model of anosmia almost 20 years ago. 1581 This study removed the OB of rats, which reli ably produced rapid apoptosis of the peripheral OSNs. Although the results indicated that minocycline did not prevent apoptosis, the time course was significantly delayed, suggesting the possibility that lesser degrees of injury might respond to minocycline. Moreover, the lim ited data available suggest that apoptosis is a common pathway for a range of human olfactory disorders, leading those authors to suggest that minocycline might serve as a broadly effective treatment for smell loss. 1582,1583,162 Based on this theoretical rationale, as well as an excel lent safety profile, a human trial of minocycline for the management of PVOL was undertaken. A total of 55 patients were randomized in a prospective, double-blind, controlled trial of 50-mg minocycline twice daily for 3 weeks and were followed for 7 months. The duration of olfactory loss was not reported. Unfortunately, there was no difference between groups in TDI score but both groups demonstrated baseline improvement in olfactory perfor mance over those 7 months. 1584 The reasons for failure are uncertain and may be related to the pathophysiology or duration of olfactory loss in postinfectious olfactory disor ders. The anti-inflammatory and neuroprotective proper ties of minocycline are currently being studied in a num ber of trials for an array of neurologic disorders, some of which have associated olfactory deficits. If minocycline, or another neuroprotective agent, is shown to be effective in reversing olfactory loss associated with the primary neuro logic disorder, it is possible that the use of this agent specif ically for olfactory disease could be revisited, but currently there is no evidence that it should be recommended for these patients. Use of minocycline for treatment of OD Aggregate grade of evidence : B (Level 1b: one study). Benefit :None.

Harm : Minimal as minocycline has a very low side effect profile. Cost : Low. Benefits-harm assessment : Slight harm possible related to low side-effect profile. Value judgments : Despite theoretical efficacy, no improvement was observed at the dose and duration used in the trial. Policy level : Recommendation against the use of minocycline for PIOD. Intervention : Minocycline should not currently be offered to patients with OD. 6 Theophylline Odorants bind to G-protein–coupled receptors within the OE and trigger an increase in intracellular cyclic adenosine monophosphate. This increase leads to depolarization and a signal transduction cascade to the OB. Phosphodiesterase inhibitors (PDEIs) increase intracellular cyclic adeno sine monophosphate and cyclic guanosine monophos phate by preventing their degradation. As such, there is a compelling mechanism by which PDEIs could poten tially enhance olfactory signal transduction in patients withOD. The clinical evidence for PDEIs, however, is mixed. In 2009, an open-label case series by Henkin et al 1585 of 312 hyposmic patients showed that 50.3% of patients had a ≥ 5% subjective improvement in olfaction after oral theophylline treatment (200–800 mg/day) and 21.7% of these reported that their OF returned to normal. This study was not performed with validated olfaction measures, con trols, or strict selection criteria so no definite conclusion can be made. Challenges with oral theophylline, includ ing tolerance and toxicity, with high levels of drug-drug interactions, led to a follow-up open-label case series using topical, intranasal theophylline. This study also showed