Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, I: analysis of cases

Holland C Detke, David P McDonnell, Elizabeth Brunner, Fangyi Zhao, Sebastian Sorsaburu, Victoria J Stefaniak, Sara A Corya, Holland C Detke, David P McDonnell, Elizabeth Brunner, Fangyi Zhao, Sebastian Sorsaburu, Victoria J Stefaniak, Sara A Corya

Abstract

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.

Trial registration: ClinicalTrials.gov ID; URL: http://http//www.clinicaltrials.gov/: NCT00094640, NCT00088478, NCT00088491, NCT00088465, and NCT00320489.

Figures

Figure 1
Figure 1
Approximate onset time of post-injection delirium/sedation syndrome events.
Figure 2
Figure 2
Post-injection delirium/sedation syndrome events and time to initial onset, incapacitation, and hospitalization. The middle line inside the box is the median 50th percentile; left border of the box is the 25th percentile and right borders of the box is the 75th percentile; left whisker is the 10th percentile and right whisker is the 90th percentile.
Figure 3
Figure 3
Approximate time to recovery from post-injection delirium/sedation syndrome events.

References

    1. Lauriello J, Lambert T, Andersen SW, Lin DY, Taylor CC, McDonnell D. An 8-week, double-blind, randomized, placebo-controlled study of olanzapine long-acting injection in acutely ill patients with schizophrenia. J Clin Psychiatry. 2008;69:790–799. doi: 10.4088/JCP.v69n0512.
    1. Kane JM, Detke HC, Naber D, Sethuraman G, Lin DY, Bergstrom RF, McDonnell DP. Olanzapine long-acting injection: a 24-week, randomized, double-blind trial of maintenance treatment in patients with schizophrenia. Am J Psychiatry. 2010;167:181–189. doi: 10.1176/appi.ajp.2009.07081221.
    1. European Medicines Agency. Assessment report for Zypadhera. 2008.
    1. Electronic Medicines Compendium. Summary of product characteristics for ZYPADHERA 210 mg, 300 mg, and 405 mg, powder and solvent for prolonged release suspension for injection. 2009.
    1. McDonnell DP, Detke HC, Kothare P, Johnson J, Stickelmeyer M, Sorsaburu S, Watson SB, Mitchell MI. Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, II: investigations of mechanism. BMC Psychiatry. 2010;10:45. doi: 10.1186/1471-244X-10-45.
    1. Downham TF, Cawley RA, Salley SO, Dal Santo G. Systemic toxic reactions to Procaine Penicillin G. Sex Transm Dis. 1978;5:4–9. doi: 10.1097/00007435-197801000-00002.
    1. Cummings JL, Barritt CF, Horan M. Delusions induced by procaine penicillin: case report and review of the syndrome. Int J Psychiatry Med. 1986;16:163–168.
    1. Institute for Safe Medication Practices. ISMP medication safety alert: Hazard warning. 1997.
    1. Institute for Safe Medication Practices. ISMP medication safety alert: Many wrongly believe long-acting parenteral penicillins are for intravenous injection. 1999.
    1. Institute for Safe Medication Practices. ISMP medication safety alert: Bicillin products: syringe enhancements may help to prevent IV administration. 2004.
    1. Do Carmo de Castro Miranda M, Rozenfeld S, Pacheco de Oliveira S. A systemic review of the non-allergic adverse reactions following benzathine benzylpenicillin injection. J Vasc Bras. 2004;3:253–260.
    1. Novocol Pharmaceuticals of Canada, Inc. Septocaine with epinephrine [package insert] 2005.
    1. Institute for Safe Medication Practices. ISMP medication safety alert: Action needed to prevent serious tissue injury with IV promethazine. 2006.
    1. Sen S, Chini EN, Brown MJ. Complications after unintentional intra-arterial injection of drugs: risks, outcomes and management strategies. Mayo Clin Proc. 2005;80:783–795. doi: 10.4065/80.6.783.
    1. Tang J, Weiter JJ. Branch retinal artery occlusion after injection of a long-acting risperidone preparation. Ann Intern Med. 2007;147:283–284.
    1. Kurtz D, Bergstrom R, McDonnell DP, Mitchell M. Pharmacokinetics of multiple doses of olanzapine long-acting injection, an intramuscular formulation of olanzapine, in stabilized patients with schizophrenia [abstract] Biol Psychiatry. 2008;63(suppl 1):288S.
    1. Mamo D, Kapur S, Keshavan M, Laruelle M, Taylor CC, Kothare PA, Barsoum P, McDonnell D. D2 Receptor occupancy of olanzapine pamoate depot using positron emission tomography: an open-label study in patients with schizophrenia. Neuropsychopharmacology. 2008;33:298–304. doi: 10.1038/sj.npp.1301409.
    1. Detke H, McDonnell D, Andersen S, Watson S. Olanzapine long-acting injection in patients with schizophrenia at risk of relapse: 12-week switching data [abstract] European Neuropsychopharmacology. 2008;18(suppl 4):S435. doi: 10.1016/S0924-977X(08)70638-2.
    1. Detke HC, McDonnell DP, Andersen SW, Watson SB. 160-week interim results from an open-label extension trial of olanzapine long-acting injection [abstract] International Journal of Neuropsychopharmacology. 2008;11(suppl 1):S151.
    1. Goldsweig HG, Kapusta M, Schwatz J. Bleeding, salicylates, and prolonged prothrombin time: three case reports and a review of the literature. J Rheumatol. 1976;3:37–42.
    1. Weis HJ, Aledort LM. Impaired platelet-connective-tissue reaction in man after aspirin ingestion. Lancet. 1967;2:495–497. doi: 10.1016/S0140-6736(67)91658-3.
    1. Weis HJ, Aledort LM, Kochwa S. The effect of salicylates on the hemostatic properties of platelets in man. J Clin Invest. 1968;47:2169–2180.
    1. Mukamal KJ, Massaro JM, Ault KA, Mittleman MA, Sutherland PA, Lipinska I, Levy D, D'Agostino RB, Tofler GH. Alcohol consumption and platelet activation and aggregation among women and men: the Framingham Offspring Study. Alcohol Clin Exp Res. 2005;29:1906–1912. doi: 10.1097/01.alc.0000183011.86768.61.
    1. Iber FL, Shamszad M, Miller PA, Jacob R. Vitamin K deficiency in chronic alcoholic males. Alcohol Clin Exp Res. 1986;10:679–681. doi: 10.1111/j.1530-0277.1986.tb05167.x.
    1. Hart A, Cohen H. Capillary fragility studies in diabetes. Br Med J. 1969;2:89–91. doi: 10.1136/bmj.2.5649.89.
    1. Purushothaman KR, Meerarani P, Moreno PR. Inflammation and neovascularization in diabetic atherosclerosis. Indian J Exp Biol. 2007;45:93–102.
    1. Beyea SC, Nicoll LH. Back to basics. Administering IM injections the right way. Am J Nurs. 1996;96:34–35. doi: 10.2307/3464849.
    1. Workman B. Safe injection techniques. Nurs Stand. 1999;13:47–53.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다