Post‐Injection Delirium/Sedation Syndrome after Olanzapine Long‐Acting Intramuscular Injection – Who is at Risk?

Abstract

The post-injection olanzapine delirium/sedation syndrome (PDSS) was observed in a 60-year-old Caucasian, schizophrenic, non-smoker and underweight [body mass index (BMI), 18.2 kg/m 2 ] women after the fourth intramuscular injection of 405 mg olanzapine pamoate. Clinical symptoms of PDSS were similar to those of acute oral olanzapine intoxication. The patient received supportive treatment and recovered fully. High olanzapine concentrations in serum, with maximum level of 698 ng/mL, were confirmed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The authors wonder whether a low BMI and advanced age may predispose patients to PDSS occurrence.Long-acting injections of antipsychotic drugs are common in psychiatric practice, especially to treat patients with schizophrenia showing non-adherence to oral pharmacotherapy [1]. A depot intramuscular formulation of olanzapine is a crystalline salt composed of olanzapine and pamoic acid. Once injected, two components of the salt dissociate into separate molecular compounds. Slow rate of dissolution allows for a gradual drug release into the circulation over 2-4 weeks [2]. This ensures an olanzapine concentration at 5-73 ng/mL, which is within the range resulting from within-label oral olanzapine doses [3]. The analysis by Heres et al. [2] revealed that the average steady-state concentrations (10th-90th percentile) for 405 mg/4-week doses were 19-62 ng/mL. In contact with increased volume of blood, the olanzapine pamoate salt dissolves more rapidly. The rapid rate of drug release occurs to very high values of olanzapine concentrations, which also depends on the level of the administered dose. Significantly elevated olanzapine blood concentrations lead to potentially severe clinical symptoms of the post-injection olanzapine delirium/sedation syndrome (PDSS) [2,4]. Case ReportA 60-year-old, Caucasian, schizophrenic, underweight [body mass index (BMI), 18.2 kg/m 2 ] women lost consciousness 10 min. after the fourth intramuscular injection of 405 mg olanzapine pamoate administered every 4 weeks. She did not receive any other medication. The patient had been suffering from schizophrenia for about 26 years, but no other chronic diseases. On the day of injection, the patient felt well and did not experience any disturbing symptoms. She had not been addicted to any psychoactive substances nor smoked cigarettes. On admission, the patient was unconscious (Glasgow Coma Scale 1 + 2 + 3 points), with bilateral miosis, periodically agitated with slight rigidity and asymmetric abnormal flexion in all four extremities. Vital signs were the following: blood pressure 140/75 mmHg, sinus tachycardia 112-130/min., respiratory rate 16 breaths/min. Due to upper airway obstruction, intubation was performed, but mechanical ventilation was not necessary. During the first 5 hr, her body temperature increased from 36.6°C to 38.2°C, so external cooling was applied. The patient was carefully observed and given symptomatic treatment. Five milligrams of intravenous midazolam loadi...

An update of safety of clinically used atypical antipsychotics

“…route of administration. In particular, post-injection delirium/sedation syndrome, characterized by sedation (including coma) and/or delirium has been reported in approximately <0.1% of injections [133][134] Patients with cardiac impairment should be carefully monitored for the increasing risk of orthostatic hypotension. Although olanzapine is not recommended in children and adolescents, preliminary clinical data suggest its relative safety and efficacy for the treatment of behavioral disturbances.…”

Post-injection syndrome and olanzapine long-acting injection in patients with schizophrenia: A case series

“…A very high serum olanzapine concentrations, sometimes exceeding 600 ng/mL, was detected in some cases. 11 Regarding management, in some cases, anti-hypertensives and benzodiazepines were used but till now no definite plan of management was mentioned in any of the previous studies. 10…”

Postinjection Delirium/Sedation Syndrome After Paliperidone Palmitate Injection in a Bipolar Affective Disorder Patient

“…4 In the literature, cases of PDSS have been mostly reported to be associated with long-acting olanzapine injections. 5,6 Kokalj et al 7 reported a female patient with schizophrenia who developed symptoms ranging from confusion to delirium and anticholinergic symptoms after a long-acting olanzapine injection and high-dose oral paliperidone. In the safety investigations of a clinical study examining the relationship between long-acting risperidone and paliperidone palmitate with PDSS, no cases of PDSS associated with paliperidone palmitate and long-acting risperidone were detected.…”

“…Postinjection delirium/sedation syndrome most commonly occurs within 5 hours after injection 4 . In the literature, cases of PDSS have been mostly reported to be associated with long-acting olanzapine injections 5,6 . Kokalj et al 7 reported a female patient with schizophrenia who developed symptoms ranging from confusion to delirium and anticholinergic symptoms after a long-acting olanzapine injection and high-dose oral paliperidone.…”