A second look on intramuscular diazepam for psychiatric emergencies

LETTERS TO THE EDITOR

A second look on intramuscular diazepam for psychiatric emergencies

Pedro Vieira da Silva Magalhães

M.D., M.Sc., Molecular Psychiatry Laboratory, Hospital de Clínicas de Porto Alegre e Universidade Federal do Rio Grande do Sul (UFRGS)

Endereço para correspondência

Even if oral medications are preferred whenever their use is possible, intramuscular application (IM) of psychotropics is frequently needed in psychiatric emergencies. Benzodiazepine use has been recommended in recent guidelines as they have a lower incidence of side-effects, especially extrapyramidal symptoms, when compared with typical antipsychotics¹.

Lorazepam has been the preferred benzodiazepine because of its reliable absorption; its parenteral formulation, however, is unavailable in Brazil. This probably explains the addition of promethazine, a sedative antihistamine, to haloperidol in our emergency rooms². This combination has the virtue of having been tested in several high quality randomized trials, with hundreds of patients exposed³. The haloperidol-promethazine mix, however, has not been tested against the combination of an antipsychotic and benzodiazepine, which is standard practice, at least in countries where parenteral lorazepam is available¹.

Intramuscular use of diazepam has been little explored in clinical research; this is probably related to pharmacokinetic difficulties related to its gluteal IM administration. Although the absorption of certain drugs following IM injection can be erratic leading to unpredictable clinical response, muscle is more vascular than subcutaneous tissue, with absorption occurring more rapidly after deltoid administration and more slowly after gluteal injections⁴. In two trials in which IM use of diazepam was examined, it was as effective as lorazepam for anxiety⁵ and as sedation before electroconvulsive therapy in chronically psychotic patients⁶.

A number of studies have demonstrated that deltoid application renders the absorption of diazepam more reliable. In one randomized, cross-over, study, absorption after deltoid injection of diazepam was rapid and complete⁷. In another experiment on healthy subjects, absorption was more rapid, having a greater clinical effect after shoulder than after thigh administration⁸.

Having those pharmacokinetic data at hand, a point can be made that deltoid administration of diazepam in addition to haloperidol could be tested in clinical trial against haloperidol and promethazine. Among benzodiazepines available in Brazil, diazepam has clear advantages over midazolam, as it is approximately 15 times cheaper and widely available for the treatment of seizures in emergency services. If deltoid administration of diazepam is demonstrated to be effective in psychiatric emergencies, patients should benefit from having another useful option for the treatment of agitation..

References

• 1. Allen MH, Currier GW, Hughes DH, Reyes-Harde M, Docherty JP. Expert Consensus Panel for Behavioral Emergencies. The Expert Consensus Guideline Series. Treatment of behavioral emergencies. Postgrad Med. 2001 (Spec No):1-88.
• 2. Huf G, da Silva Freire Coutinho E, Fagundes HM Jr, Oliveira ES, Lopez JR, Gewandszajder M, et al. Current practices in managing acutely disturbed patients at three hospitals in Rio de Janeiro-Brazil: a prevalence study. BMC Psychiatry. 2002;2:4.
• 3. Huf G, Alexander J, Allen MH. Haloperidol plus promethazine for psychosis induced aggression. Cochrane Database Syst Rev. 2005 Jan 25;(1):CD005146.
• 4. Tuttle CB. Intramuscular injections and bioavailability. Am J Hosp Pharm. 1977;34(9):965-8.
• 5. Ananth J, Van den Steen N. Intramuscular lorazepam. A double-blind comparison with diazepam and placebo. Neuropsychobiology. 1983;9(2-3): 139-41.
• 6. Rousos AP, Hazlewood R, Orr R. Intramuscular diazepam as anti-anxiety agent in SCC-modified EST. Dis Nerv Syst. 1969;30(11):752-7.
• 7. Divoll M, Greenblatt DJ, Ochs HR, Shader RI. Absolute bioavailability of oral and intramuscular diazepam: effects of age and sex. Anesth Analg. 1983;62(1):1-8.
• 8. Korttila K, Linnoila M. Absorption and sedative effects of diazepam after oral administration and intramuscular administration into the vastus lateralis muscle and the deltoid muscle. Br J Anaesth. 1975;Aug;47(8): 857-62.

Publication Dates

• Publication in this collection
  28 Aug 2009
• Date of issue
  2009