Benzodiazepines are considered the mainstay of therapy in the management of anxiety in palliative care.

DIAZEPAM
- Diazepam has a wide therapeutic index (wide margin of safety against toxicity) and high oral bioavailability (~100%).
- The onset of action following oral administration is around 15 minutes.
- Duration of effect: 3-30 hours (slow/fast metabolizers). The plasma half-life is 20-100 hours; active metabolite nordiazepam, 30-200 hours.
- The injection is not suitable for subcutaneous administration.

LORAZEPAM
- Lorazepam has an oral bioavailability of 93%.
- The onset of action following sublingual administration is 5 minutes, and following oral administration is 10-15 minutes.
- Injection can be administered by the sublingual route but is not recommended for subcutaneous administration.
- Plasma half-life is much shorter than diazepam (12-15 hours), which makes it useful as a pn medication. However, the duration of effect does not correlate with plasma concentrations and can be longer (up to 72 hours).

Additional supporting information for benzodiazepines
- No evidence of improved efficacy of one benzodiazepine over another has been identified. Expert opinion strongly supports the use of lorazepam and diazepam for treatment of anxiety.
- Lorazepam may be preferred to diazepam for treating acute attacks because of the rapid onset of effect when administered sublingually; it also tends to cause less sedation.
- Lorazepam is the preferred agent for the prolonged treatment of anxiety in the critically ill adult.
- Diazepam may be more appropriate for chronic anxiety symptoms because of its medium-to-long half-life.
- Lorazepam is available as an expidet tablet of 1 mg or 2.5 mg. This application form can be used sublingually, providing a quick onset of effect, and it also makes it suitable for patients who are unable to swallow, either because of impairment of the gastrointestinal passage or because of reduced consciousness level.
- There are no studies comparing the safety or efficacy of one benzodiazepine over another. The choice(s) of agent is therefore likely to be determined by availability of suitable formulations, route of administration, pharmacokinetics, and clinical preference.

A combination of psychotherapeutic and pharmacological approaches has proven to be more effective than administering these treatments separately.

Recommended medicines: DIAZEPAM and LORAZEPAM
Recommended formulations:
Diazepam:
Injection: 5 mg/mL.
Oral liquid: 2 mg/5 mL.
Rectal solution: 2.5 mg; 5 mg; 10 mg.
Tablet: 5 mg; 10 mg.
Lorazepam:
Parenteral formulation: 2 mg/mL in 1-mL ampoule.
Tablet: 1 mg and 2.5 mg.

Adapted from Radbruch L et al. Essential medicines in palliative care — An application for the 19th WHO Expert committee on the selection and use of essential medicines. Kindle Edition, 135 pages. Published June 5, 2013 by IAHPC Press. Available at https://www.amazon.com/Essential-Medicines-Palliative-Care-Application-ebook/dp/B00D7S2D0C