What works faster, sublingual (under the tongue) lorazepam (Ativan), or sublingual alprazolam (Xanax)?

From the Guidelines

Sublingual alprazolam works faster than sublingual lorazepam due to its better lipid solubility, which allows it to cross the oral mucosa more rapidly and enter the bloodstream more quickly. When considering the management of anxiety or agitation, as outlined in the NICE guidelines for managing COVID-19 symptoms in the community 1, the choice between sublingual lorazepam and sublingual alprazolam should be based on their pharmacokinetic properties and onset of action. Key points to consider include:

• The onset of action for sublingual alprazolam is typically within 10-15 minutes, while lorazepam usually takes about 15-30 minutes to start working.
• Alprazolam's better lipid solubility allows it to be absorbed more quickly through the sublingual route.
• Lorazepam can be used orally or sublingually (off-label use), with recommended doses of 0.5-1 mg orally four times a day as required, and reduced doses for elderly or debilitated patients 1.
• Individual responses to these medications may vary, and they should only be taken as prescribed by a healthcare provider.
• Sublingual administration may provide faster relief than oral tablets, but it should only be used if specifically directed by your doctor, as not all formulations are designed for sublingual use.

From the FDA Drug Label

Peak concentrations in plasma occur approximately 2 hours following administration A mean half-life of alprazolam of 16.3 hours has been observed in healthy elderly subjects (range: 9 to 26. 9 hours, n = 16) compared to 11 hours (range: 6.3 to 15.8 hours, n = 16) in healthy adult subjects.

The FDA drug label does not answer the question about which works faster, sublingual lorazepam or sublingual alprazolam, as it does not provide a direct comparison of the two drugs' onset of action or time to peak effect. 2 3

From the Research

Comparison of Sublingual, Lorazepam, and Sublingual Alprazolam

• The study 4 compared the absorption of alprazolam after sublingual and oral administration, and found that the peak plasma concentration after sublingual dosage was higher than after oral administration, although the difference did not reach statistical significance.
• The time of peak concentration following sublingual administration was reached faster than after oral administration (1.17 vs. 1.73 hours after dose).
• Another study 5 discussed the role of benzodiazepines in the treatment of epilepsy, and mentioned that non-intravenous routes of midazolam should be considered as an equally efficacious alternative to intravenous lorazepam.
• However, there is no direct comparison between sublingual, lorazepam, and sublingual alprazolam in terms of onset of action.
• A study 6 reviewed the clinical results of high-potency benzodiazepines, including alprazolam and lorazepam, but did not provide a direct comparison of their onset of action.
• Another study 7 discussed the uses, dangers, and clinical considerations of benzodiazepines, and mentioned that they quickly diffuse through the blood-brain barrier to affect the inhibitory neurotransmitter GABA and exert sedative effects, but did not provide a direct comparison of the onset of action of different benzodiazepines.

Onset of Action

• The study 4 found that the time of peak concentration following sublingual administration of alprazolam was reached faster than after oral administration.
• The study 5 mentioned that time to treatment is crucial in the treatment of status epilepticus, and that non-intravenous routes of midazolam should be considered as an equally efficacious alternative to intravenous lorazepam.
• However, there is no direct comparison between the onset of action of sublingual, lorazepam, and sublingual alprazolam.
• A study 8 discussed the clinical measures of rapid onset of action, but it was in the context of antidepressants, not benzodiazepines.