Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, I: analysis of cases.
BACKGROUND
An advance in the treatment of schizophrenia is the development of long-acting intramuscular formulations of antipsychotics, such as olanzapine long-acting injection (LAI). During clinical trials, a post-injection syndrome characterized by signs of delirium and/or excessive sedation was identified in a small percentage of patients following injection with olanzapine LAI.


METHODS
Safety data from all completed and ongoing trials of olanzapine LAI were reviewed for possible cases of this post-injection syndrome. Descriptive analyses were conducted to characterize incidence, clinical presentation, and outcome. Regression analyses were conducted to assess possible risk factors.


RESULTS
Based on approximately 45,000 olanzapine LAI injections given to 2054 patients in clinical trials through 14 October 2008, post-injection delirium/sedation syndrome occurred in approximately 0.07% of injections or 1.4% of patients (30 cases in 29 patients). Symptomatology was consistent with olanzapine overdose (e.g., sedation, confusion, slurred speech, altered gait, or unconsciousness). However, no clinically significant decreases in vital signs were observed. Symptom onset ranged from immediate to 3 to 5 hours post injection, with a median onset time of 25 minutes post injection. All patients recovered within 1.5 to 72 hours, and the majority continued to receive further olanzapine LAI injections following the event. No clear risk factors were identified.


CONCLUSIONS
Post-injection delirium/sedation syndrome can be readily identified based on symptom presentation, progression, and temporal relationship to the injection, and is consistent with olanzapine overdose following probable accidental intravascular injection of a portion of the olanzapine LAI dose. Although there is no specific antidote for olanzapine overdose, patients can be treated symptomatically as needed. Special precautions include use of proper injection technique and a post-injection observation period.


BACKGROUND
ClinicalTrials.gov ID; URL: http://http//www.clinicaltrials.gov/: NCT00094640, NCT00088478, NCT00088491, NCT00088465, and NCT00320489.
Detke
Holland C
HC
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA. detkehc@lilly.com
McDonnell
David P
DP
Brunner
Elizabeth
E
Zhao
Fangyi
F
Sorsaburu
Sebastian
S
Stefaniak
Victoria J
VJ
Corya
Sara A
SA
D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D003072:Cognition Disorders; D003692:Delayed-Action Preparations; D003693:Delirium / Q000139:chemically induced* / Q000453:epidemiology; D004334:Drug Administration Schedule; D062787:Drug Overdose / Q000453:epidemiology / Q000209:etiology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000378:metabolism; D006801:Humans; D015994:Incidence; D007273:Injections, Intramuscular; D000077152:Olanzapine; D012307:Risk Factors; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy*; D012890:Sleep / Q000187:drug effects; D013577:Syndrome; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D001569:Benzodiazepines; D000077152:Olanzapine