Coadministration of intramuscular olanzapine and benzodiazepines in agitated patients with mental illness

Abstract

Introduction:Intramuscular antipsychotics are commonly used to manage agitated patients. In 2005, Eli Lilly placed a warning on olanzapine's prescribing information following post-marketing reports of fatal drug reactions when intramuscular olanzapine was used in the setting of benzodiazepines. Data is lacking examining this drug combination.Methods:A medication use evaluation was conducted at a county psychiatric hospital surveying the usage of concomitant intramuscular olanzapine and lorazepam from October 1, 2016, to July 20, 2017. A literature search was conducted to review available evidence.Results:Ninety-one instances of the drug combination were discovered, with no serious adverse events following administration. Of these 91 patients, 41 received both medications within 60 minutes of each other. No instances of hypotension, bradycardia, bradypnea, or oxygen desaturation occurred following administration. The literature review yielded 1 randomized, placebo-controlled clinical trial, 3 retrospective chart reviews, and several case studies.Discussion:Data detailing a causal relationship between olanzapine/benzodiazepine combinations and serious adverse effects is lacking. Available evidence does not consistently support a strong cause and effect relationship. The results of this medication use evaluation are not consistent with the Food and Drug Administration warning. Further controlled research is needed to help define the actual risk of using concomitant intramuscular olanzapine and benzodiazepines.

Improving the management of acutely agitated patients in the emergency department through implementation of Project BETA (Best Practices in the Evaluation and Treatment of Agitation)

“…TA B L E 3 Pharmacology for the agitated patients 11,35,[38][39][40][41][42][43][44][45][46][47][48][49][50][51][52] 61 and document this in the electronic medical record where it is easily visible on the patient tracking board. A special wrist band is placed on the patient, and a sign is placed on their doorway to alert all healthcare workers of the violence risk.…”

Intravenous Olanzapine for the Management of Agitation: Review of the Literature

“…18 Despite additional recent retrospective data suggesting the potential safety of this combination, current recommendations remain the same until higher-quality evidence is available. 2,18…”

“…The synergistic effect of the concomitant administration of parenteral benzodiazepines and IM olanzapine increases the risk of excessive sedation, cardiorespiratory depression, and mortality in some cases. 18 Postmarketing mortality data of 29 patients who received the combination was detailed by Marder et al 19 These reports ultimately led to the addition of FDA warnings against coadministration of IM olanzapine and benzodiazepines in the prescribing guidelines. 19 When examining these reports more closely, it is difficult to establish a cause and effect relationship between the combination of IM olanzapine and IM benzodiazepines with fatality.…”

“…In cases of fatality, nearly half of the patients had comorbid medical illness, suicide attempts, or substance intoxication, which confounds findings. 18 Despite additional recent retrospective data suggesting the potential safety of this combination, current recommendations remain the same until higher-quality evidence is available. 2,18 Cardiovascular adverse effects were reported in the different trials, and rates of hypotension, bradycardia, and tachycardia were not statistically different among the different groups/arms of the studies.…”

Synthetic cannabinoids and potential cardiac arrhythmia risk: an important message for drug users

“…For cases where benzodiazepines do not suffice or are contraindicated, it should be noted that a recent meta-analysis found that intramuscular olanzapine was less likely to be associated with QT prolongation than haloperidol, making it the agent of choice for management of SCRA-related behavioural disturbance where IM medication is required. 19 It is worth noting that where IM olanzapine is given to patients already receiving benzodiazepines, and although a recent analysis has highlighted a lack of data causally linking this combination with severe adverse effects, 20 careful monitoring to avoid respiratory depression is nevertheless probably prudent. Further work is certainly warranted to evaluate the actions of key SCRAs on determinants of ventricular repolarization and to explore interactions between cardiac effects of these drugs and commonly used medications, including psychotropic drugs and methadone.…”