This week on PsyQ, we dive into the controversial practice of co-administering parenteral olanzapine and benzodiazepines for agitation. We revisit the 2005 FDA warning prompted by post-marketing reports (Marder et al., 2010) and critically examine the causality behind the reported fatalities. Contrasting this, we explore subsequent research, including observational studies (Williams, 2018; Wilson et al., 2012), an RCT using IV formulations (Chan et al., 2013), and a large recent retrospective study (Cole et al., 2024), which suggest the combination may be safer than the initial warning implied, finding no significant increase in severe cardiorespiratory events like intubation compared to olanzapine alone, even within 60 minutes and in patients with alcohol intoxication. We discuss the differing regulatory stances (FDA vs. EMA), practical implications, patient selection (caution with respiratory compromise/alcohol), and how this evolving evidence landscape might impact clinical decision-making in managing acute agitation.
Key Studies Discussed:
Marder SR et al. (2010): Original post-marketing case reports leading to the warning. J Clin Psychiatry.
Williams AM (2018): MUE finding no SAEs with IM olanzapine + lorazepam. Ment Health Clin.
Wilson MP et al. (2012): Compared olanzapine+benzo vs haloperidol+benzo; highlighted alcohol risk. J Emerg Med.
Chan EW et al. (2013): RCT showing safety of IV olanzapine + midazolam. Ann Emerg Med.
Cole JB et al. (2024): Large retrospective study finding no difference in intubation/hypoxia/hypotension rates between olanzapine+benzo vs olanzapine x2. Ann Emerg Med.
Carlat Psychiatry Report Summary: Overview and clinical take on the evidence.
This podcast is AI generated with human input and review, however there may be errors, so for the most accurate and up to date information, please consult the primary sources.
