Effects of Intramuscular Midazolam and Lorazepam on Acute Agitation in Non-Elderly Subjects – A Systematic Review

Abstract

Benzodiazepines are commonly used for the treatment of acute agitation in a psychiatric setting.We searched MEDLINE, EMBASE, PsycINFO, and the Cochrane Central Register of Controlled Trials (CENTRAL) for relevant publications. Randomized trials evaluating intramuscular (IM) midazolam or lorazepam given as monotherapy or as add-on treatment, with more than 10 patients aged 18-65 years, conducted in a psychiatric setting, and published between January 1, 1980, and February 3, 2016, were included. 16 studies from a search result of 5 516 studies were included. In total, 577 patients were treated with lorazepam IM 2-4 mg, and 329 patients were treated with midazolam IM 5-15 mg. It is unclear whether lorazepam IM or midazolam IM is as efficacious as an antipsychotic IM. It is a bit more certain that the combination of benzodiazepines IM and a low dose antipsychotic IM is more efficacious than the benzodiazepine and the antipsychotic alone. However, there is no doubt that benzodiazepines are less likely to be associated with treatment emergent side effects, as compared to antipsychotics.

Interrogating systematic review recommendations for effective chemical restraint

“…• Twelve SRs provided no information on consent, either in the search terms or data extraction tables. 25,29,32,35,38,41,44,47,50,53,55,56 One further SR 26 reported an evidence review for a clinical guideline with details supposedly available in a nonoperational link (which meant the methods could not be checked).…”

“… Only one SR in this group dealt with effectiveness and/or safety of medications (haloperidol, an antipsychotic drug) 51 ; Ten SRs did not include “consent” in their search strategies, but they reported on this in data extraction tables 24,0031,0034,0037,0040,0043,0046,0049,0052,0054 . These SRs included primary papers reporting on consenting patients, as well as primary papers reporting on nonconsenting patients (which we labelled mixed consent). All 10 SRs reported on effectiveness and/or safety of benzodiazepines and/or antipsychotic drugs; Twelve SRs provided no information on consent, either in the search terms or data extraction tables 29,32,35,38,41,44,47,50,53,55,56 . One further SR 26 reported an evidence review for a clinical guideline with details supposedly available in a nonoperational link (which meant the methods could not be checked). All 12 SRs reported on effectiveness and/or safety of benzodiazepines and/or antipsychotic drugs. …”

“…The 23 SRs, 24,25,29,31,32,34,35,37,38,40,41,43,44,46,47,49,50,51,52,53,54,55,56 which all reported on CR drugs, and the umbrella SR, 28 were appraised for methodological quality using the JBI SR checklist 22…”

“…The 23 SRs, 24,25,29,31,32,34,35,37,38,40,41,43,44,46,47,[49][50][51][52][53][54][55][56] which all reported on CR drugs, and the umbrella SR, 28 were appraised for methodological quality using the JBI SR checklist. 22 T A B L E 1 Information on consent provided in the identified SRs, linked with the title of the review To estimate the effects of IM, oral-velotab, or standard oral olanzapine compared with placebo, haloperidol or lorazepam for controlling aggressive behaviour or agitation thought to be due to severe mental illness…”

Spontaneous recovery of traumatic brain injury-induced functional deficits is not hindered by daily administration of lorazepam

“…Because the mechanism of action for LOR differs from that of HAL and risperidone, it is hypothesized that LOR would not impede motor and cognitive recovery when provided chronically after TBI. While several excellent reviews and studies exist discussing the use and efficacy of benzodiazepines in general [42–44] and LOR specifically [26,45–49] to manage agitation after clinical brain injury, there are no experimental studies evaluating LOR after experimental TBI. Hence, the current study was designed to investigate a dose response of LOR on neuromotor and cognitive performance after cortical impact injury in rats.…”