Sublingual triazolam for the provision of anxiolysis in the dental setting

triazolam in dental setting
Both proponents and critics of the provision of powdered doses of sublingual triazolam agree that demand exists for the relief of anxiety during outpatient dental care. However, more studies are required to better inform and document the effects of this clinical regimen.

To date, pharmacokinetic studies of sublingual administration have not been relevant to clinical practice, primarily because this research has only been performed upon healthy volunteers. These studies have used different formulation and protocols of incremental dosing that do not correspond to clinical practice.

This study was designed to determine the pharmacokinetics and sedative effects of incremental sublingual dosing of triazolam (total, 1.0 mg) in healthy adults. Ten adult volunteers received sublingual triazolam (0.25 mg) followed by additional doses after 60 (0.50 mg) and 90 (0.25 mg) minutes.


Hypothesis 1a: Powdered sublingual triazolam has significantly higher peak plasma and saliva levels than oral triazolam

Hypothesis 1b: Powdered sublingual triazolam has significantly earlier onset of action than oral triazolam

Hypothesis 2: Triazolam levels in saliva significantly correlate with plasma levels at all times


25 healthy volunteers, NPO for 6 hours
Baseline measurements of:
         Plasma and saliva levels
         Sedation Scale, Anxiety Scale
         Digital Subtraction Cognitive Function Measurement

0.25 mg triazolam crushed, administered sublingually or 0.25 mg p.o.,
Repeat measurements every 30 minutes for 360 minutes
Standard gas chromatographic measurements of plasma levels
         Commercial kit analysis of saliva levels
         Statistical analysis

In conclusion, it appears that the sublingual administration of triazolam can result in earlier and higher peak concentrations than the oral administration. Although gain may be obtained in the onset of action and ease of use for patients by administering triazolam sublingually, the results of this study do not indicate any advantages for the development of a fast-dissolving sublingual formulation of triazolam. In addition, the extensive presystemic metabolism was an unexpected observation that likely contributes to the variability in triazolam.


Sublingual triazolam resulted in significantly less anxiety and pain at 15 minutes intraoperatively than both oral triazolam and the placebo (p < 0.05). Patients' global evaluation of the efficacy of sedation ranked sublingual triazolam as significantly more efficacious than the placebo (p < 0.05) with oral triazolam intermediate between the two. No difference was demonstrated in the rate of recovery or the incidence of side effects between the two drug groups. Plasma triazolam levels were higher after sublingual administration during and after the surgical procedure.


These results indicate that sublingual triazolam results in greater anxiolytic activity and less pain perception than oral administration as a result of greater plasma drug levels and may be useful as an alternative for nonparenteraI outpatient sedation.