Recommended medicines: DIAZEPAM and LORAZEPAM
Injection: 5 mg/mL
Oral liquid: 2 mg/5 mL
Rectal solution: 2.5 mg; 5 mg; 10 mg.
Tablet: 5 mg; 10 mg.
Parenteral formulation: 2mg/mL in 1-mL ampoule
: tablets 1mg and 2.5mg
• Anxiety is defined as the apprehensive anticipation of future danger or misfortune accompanied by a feeling of dysphoria or somatic symptoms of tension. The focus of anticipated danger may be internal or external.
• Anxiety is characterized by excessive feelings of fear apprehension and worry. Anxiety may be associated with symptoms of depression, poor concentration, insomnia, irritability, panic attacks, sweating, tremor and nausea.
• Anxiety is frequent in palliative care.
• A combination of psychotherapeutic and pharmacological approaches has proven to be more effective than administering these treatments separately.
Overview of pharmacological management options
Benzodiazepines are considered the mainstay of therapy in the management of anxiety in palliative care. However, there are no good quality studies on the role of benzodiazepines (or other drugs) in the treatment of anxiety in palliative care to draw a conclusion about their efficacy. Evidence of use in palliative care is based on expert opinion
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 metabolisers). The plasma half-life is 20-100 hours; active metabolite nordiazepam 30-200 hours.
The injection not suitable for subcutaneous administration.
has an oral bioavailability of 93%
The onset of action following sublingual administration is 5 min and following oral administration is 10-15 min.
Injection can be administered by the sublingual route but is not recommended for subcutaneous administration.
Plasma half-life much shorter than diazepam
(12-15 hours) which makes it useful as a prn 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 was identified. Considering the lack of evidence from clinical trials, the recommendation for benzodiazepines has to be based on clinical expertise. formulations, route of administration, pharmacokinetics and clinical preference. Expert opinion strongly supports the use of lorazepam
for treatment of anxiety.
may be preferred to diazepam for treating acute attacks because of the rapid onset of effect when administered sublingually and it also tends to cause less sedation.
is the preferred agent for the prolonged treatment of anxiety in the critically ill adult.
may be more appropriate for chronic anxiety symptoms because of its medium too long half-life.
is available as an expidet tablet with 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.
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 5th 2013 by IAHPC Press. Available at https://www.amazon.com/Essential-Medicines-Palliative-Care-Application-ebook/dp/B00D7S2D0C