Post-Injection Delirium/Sedation Syndrome in Patients Treated with Olanzapine Pamoate: Mechanism, Incidence, and Management

Abstract

Second-generation antipsychotics (SGAs) are a mainstay in the treatment of patients with schizophrenia. However, continuity in intake of the prescribed medication has been one of the greatest challenges in these patients. One option to improve medication adherence is to prescribe depot or long-acting injectable formulations (LAIs) of antipsychotics. Following risperidone, several other SGAs have been introduced as LAIs. Olanzapine pamoate, paliperidone palmitate, and aripiprazole are the new-generation LAIs, which are available for 2- to 4-week intervals of application in many countries. The literature shows a clear advantage of these drugs over placebo regarding symptom reduction and relapse prevention. LAIs show a similar safety profile to oral formulations of the relevant drug, with the exception of olanzapine pamoate, which can lead to rare cases of post-injection delirium/sedation syndrome (PDSS). PDSS is characterized by heavy sedation (possibly including coma) and/or delirium after injection. During PDSS events, patients show higher plasma concentrations of olanzapine, leading to the assumption that unintended partial intravascular injection or blood vessel injury during the injection is causative of PDSS. Therefore, a risk-management plan proposing an observation period of 3 h was introduced. In August 2013, a new proposal by the European Medicines Agency terminated the requirement to accompany these patients to their next destination, although this requirement remains in place according to US FDA recommendations.

Long-acting injectable antipsychotics for prevention and management of violent behaviour in psychotic patients

“…While the profile of side effects corresponds to that observed in short-acting oral formulations of the respective drugs, some other adverse events associated with LAI administration, in addition to injection site complications, may occur. For example, post-injection syndrome has been associated with LAI olanzapine pamoate 34. The potential risk of this serious medical condition, most likely caused by an accidental overdose, requires all patients treated with olanzapine LAI to be monitored for three hours after drug administration.So far, there are only two published studies (one retrospective cohort study, one randomised double-blind trial) comparing efficacy of first-generation (FGA) and second-generation (SGA) LAI 35,36.…”

Postinjection Delirium Syndrome Associated With Olanzapine Long-Acting Injectable

“…3 Current data regarding occurrence, development, manifestation, treatment, and outcome of PDSS are still limited. In a review article published in CNS Drugs 2015, the authors claim that only one case of PDSS has been mentioned in connection with OLAI since the last clinical trial ended in August 2008, 11 whereas a recent study based on postmarketing safety studies and spontaneous reports found a total of 338 PDSS events between March 1, 2009, and March 1, 2014. 3 Regulatory authorities have established risk management mitigation programs.…”

Clinical outcomes with olanzapine long-acting injection: impact of the 3-hour observation period on patient satisfaction and well-being

“…The identification of PDSS ultimately resulted in the European label for olanzapine LAI having a risk minimization plan associated with it, the key elements being a 3-hour observation period and for patients to be accompanied home at the end of this 3-hour time period 3. In 2013, the European Medicines Agency announced that the safety signal of olanzapine LAI was sufficient to warrant the removal of the requirement of patients to be accompanied home, but the mandatory stipulation of the 3-hour observation period still remains 3,5…”

“…In 2013, the European Medicines Agency announced that the safety signal of olanzapine LAI was sufficient to warrant the removal of the requirement of patients to be accompanied home, but the mandatory stipulation of the 3-hour observation period still remains 3,5…”