2011; Phillips, 2011]. The other benzodiazepines most commonly used worldwide for rapid tranquillization are clonazepam and midazolam. TGX-221 Midazolam has a faster onset than lorazepam but requires

more frequent re-administration and has an increased risk of respiratory depression [Bak et al. 2011]. Many units have been using intramuscular clonazepam as an alternative benzodiazepine although the intramuscular route of administration is unlicensed in the Inhibitors,research,lifescience,medical UK (Marion Wetherill, Personal communication, Medical Information Department, Roche Products Ltd, 2010). Clonazepam has been reported to be used in doses up to 6 mg for rapid tranquillization in adults since the early 1990s with few side effects to produce similar tranquillization to haloperidol in a similar timeframe [Chouinard

Inhibitors,research,lifescience,medical et al. 1993]. However, there are no reports about its use in adolescent patients. Compared with lorazepam, clonazepam is associated with pharmacokinetic differences that have the potential to cause concern. Clonazepam has a slower time to peak concentration Inhibitors,research,lifescience,medical of 3 hours [Crevoisier et al. 2003] compared with a time of 1.5 hours for lorazepam [Wyeth Pharmaceuticals, 2005]. In terms of dose equivalence, 1 mg lorazepam is reported to be equivalent to 0.25–0.5 mg clonazepam [Curtin and Schulz, 2004]; however, the Maudsley guidelines [Taylor et al. 2009] state that 1 mg lorazepam is equivalent to 1–2 mg clonazepam. Information obtained from the manufacturer in 2005 gave a dose equivalence of 1–2 mg lorazepam being equivalent to 4 mg clonazepam. These differences illustrate the uncertainty of actual dose equivalence. The elimination half-life of clonazepam

is relatively long with estimates varying between 20 and 80 hours [Greenblatt et al. 1987; Berlin and Dahlstrom, 2010]. Another Inhibitors,research,lifescience,medical source reports clonazepam’s half-life to be 39 hours with that of lorazepam being 11 hours [Davies et al. 2010]. This gives the potential for dose accumulation when doses are repeated in succession. In addition, it is reported that there are secondary peaks observed following intravenous or intramuscular clonazepam, thought to be due to enterohepatic Inhibitors,research,lifescience,medical recycling, because the glucuronide of clonazepam may be deconugated by intestinal flora and reabsorbed from the intestine in the form of the parent drug [Davies Calpain et al. 2010]. In terms of brain uptake and benzodiazepine receptor occupancy, clonazepam has been found to be similar to lorazepam [Greenblatt et al. 1987]. Respiratory depression is a well-recognized but rare side effect of benzodiazepine’s, although this is increased if the benzodiazepine is taken with alcohol or is given to someone who has underlying pulmonary problems [McNaught et al. 1989]. In an adolescent forensic secure hospital it is not uncommon to require the use of intramuscular rapid tranquillization medication in the management of severe aggression and agitation for patients as young as 13 years [Hill et al. 2012].