xRead - Olfactory Disorders (September 2023)

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608

INTERNATIONAL CONSENSUS ON OLFACTION

TABLE IX-37 (Continued)

Clinical end point Subjective and objective psy chophysical measure ments

Study

Year LOE Drug

Study design Study groups

Conclusions

Objective Shh levels in nasal mucus were associated with subjective improvement in olfaction after 2 to 10 months of treatment Intranasal theophylline for 6 weeks yielded minimal objective improvement of odor identification in 5 of 7 patients with ESRD

Case series

58 patients with

Henkin

2017 4

Oral theophylline 200 to 800 mg daily

et al 1592

hyposmia (n = 44) and HCs (n = 14)

Nigwekar et al 484

2017 4

Intranasal

Case series

7 patients with

UPSIT R

theophylline 20 μ g each naris daily

ESRD and mild OD

and hyposmia, although below MCID

Stafford

Regular consumers of coffee had an enhanced sensitivity

Threshold tests for coffee and n-butanol odors

2020 3

Caffeine

Cohort

Coffee consumers (n = 41) and nonconsumers (n = 21)with normal olfaction

et al 1593

to coffee odor by objective testing

Whitcroft et al 1589

2020 4

Pentoxifylline oral, 600 mg daily

Case series

6patients

SS-TDI

Oral pentoxifylline for 21 days did not appear to be beneficial in the treatment of hyposmia in this group

posttraumatic hyposmia

cAMP = cyclic adenosine monophosphate; cGMP = cyclic guanosine monophosphate; ESRD = end-stage renal disease; HC = healthy control; LOE = level of evidence; MCID = minimum clinically important difference; OD = olfactory dysfunction; OF = olfactory function; PDEI = phosphodiesterase inhibitor; SS-D = Sniffin’ Sticks discrimination only; SS-T = Sniffin’ Sticks threshold only; SS-TDI = Sniffin’ Sticks threshold, discrimination, identification combination; UPSIT R = University of Pennsylvania Smell Identification Test.

improvement in OF in 8 of 10 patients after 4 weeks of treatment, but suffered from the same weaknesses as the prior. 1586 Most recently, in an open-label clinical trial of a very small number of patients with end-stage renal disease and OD, five of seven patients improved with topical, intranasal theophylline (20 μ g/day for 6 weeks), although this minimal improvement was below the MCID. 484 Theophylline is the most investigated PDEI in the treat ment of OD; however, caffeine, sildenafil, and pentoxi fylline have also been studied. In a double-blind, placebo controlled trial of 76 patients with hyposmia, a single dose of 65 mg of caffeine (eg, espresso) showed no effect on OF. 1587 Additionally, a trial of 20 healthy male volun teers also found no effect of sildenafil on olfaction at 50 mg and, surprisingly, decreased OF was seen at 100 mg, presumably because of nasal congestion. 364 Furthermore, pentoxifylline administered (intravenously or orally) in 19 patients with otologic conditions demonstrated some

improvement in odor threshold scores; however, overall objective olfactory measures did not improve. 1588 Most recently, six patients with posttraumatic hyposmia were administered 200 mg/day of this medication, with some small nonsignificant improvements in odor threshold and identification scores. 1589 Although there is some Level 2 to 4 evidence to sug gest that theophylline may provide subminimally clinical important difference improvement in OF by both oral and topical administrations, definitive conclusions are not able to be made because of limitations in study design. Specifi cally, these studies do not account for spontaneous olfac tory recovery given the lack of a control arm, include a heterogenous group of olfactory loss causes, and rely on subjective assessments rather than validated instruments. PDEIs other than theophylline (eg, caffeine, sildenafil, and pentoxifylline) have not been shown to provide clinically meaningful benefit in patients in the treatment of olfactory loss.