What is Post Injection Delirium Sedation Syndrome (PDSS) and how is it managed?

Post-Injection Delirium/Sedation Syndrome (PDSS)

Definition and Clinical Presentation

Post-Injection Delirium/Sedation Syndrome (PDSS) is a rare but potentially life-threatening adverse reaction occurring specifically after intramuscular administration of long-acting injectable olanzapine pamoate, characterized by acute onset of sedation, delirium, dysarthria, ataxia, extrapyramidal symptoms, agitation, dizziness, or seizure. 1, 2, 3

Key Clinical Features

• Incidence: Occurs in approximately 0.07% of injections or 1.4% of patients receiving olanzapine long-acting injection 4
• Timing: Symptoms typically develop shortly after injection administration 2, 3
• Symptom constellation: Most commonly presents with sedation and delirium, but may include dysarthria, ataxia, extrapyramidal symptoms, agitation, dizziness, or seizures 1, 3
• Mechanism: The exact pathophysiology remains unclear, though it is hypothesized to relate to inadvertent intravascular injection or rapid absorption of olanzapine 1, 3

Specificity to Olanzapine LAI

PDSS has been demonstrated to occur exclusively with olanzapine pamoate long-acting injection; it has not been documented with other long-acting injectable antipsychotics including risperidone microspheres, paliperidone palmitate, fluphenazine decanoate, or haloperidol decanoate. 4

• Analysis of 15 clinical trials of risperidone LAI and 10 trials of paliperidone palmitate failed to demonstrate any PDSS events in patients receiving these medications 4
• One case of PDSS-like symptoms was identified in a placebo group, suggesting the syndrome is not a class effect of LAI antipsychotics 4

Prevention Protocol

The most critical preventive measure is mandatory 3-hour post-injection observation of all patients receiving olanzapine long-acting injection, with continuous monitoring of vital signs and mental status. 1, 2, 3

Observation Requirements

• Duration: Minimum 3 hours of direct observation after each injection 1, 2
• Monitoring parameters: Vital signs (blood pressure, heart rate, respiratory rate, oxygen saturation) and mental status assessment 2, 3
• Patient restrictions: Patients should not drive or operate machinery for the remainder of the day after injection 3
• Facility requirements: Observation must occur in a setting with immediate access to emergency medical care 2, 3

Emergency Management

Immediate Actions

• Activate emergency response: Transfer to emergency department or intensive care setting immediately upon recognition of symptoms 3
• Airway protection: Assess and secure airway; prepare for potential mechanical ventilation if severe sedation or altered mental status develops 3
• Supportive care: Provide aggressive supportive measures including IV access, continuous cardiac monitoring, pulse oximetry, and frequent vital sign assessment 3
• Avoid pharmacologic reversal: There is no specific antidote for PDSS; benzodiazepines should be avoided as they may worsen sedation and delirium 3

Diagnostic Workup

• Measure olanzapine plasma concentrations: Obtain serum olanzapine levels to confirm diagnosis and guide duration of monitoring 1
• Rule out alternative diagnoses: Exclude serotonin syndrome (particularly if patient takes SSRIs), neuroleptic malignant syndrome, stroke, seizure, or other acute neurologic events 3, 5
• Baseline laboratory studies: Complete metabolic panel, complete blood count, and toxicology screen to exclude metabolic or toxic causes 3

Therapeutic Approach

• Symptomatic management only: Treatment is entirely supportive; no pharmacologic intervention has proven benefit 3
• Mechanical ventilation: May be required for severe cases with respiratory compromise 1, 3
• Duration of monitoring: Continue intensive monitoring until complete resolution of symptoms, which may take several hours to days depending on severity 1, 3
• Avoid antipsychotics: Do not administer additional antipsychotic medications, as this may worsen symptoms 3

Prognosis and Long-Term Outcomes

Patients who experience PDSS typically make complete recovery without long-term neurologic sequelae, disability, or post-traumatic stress disorder when appropriately managed. 1

• Follow-up data at 2.5 years post-event demonstrates full recovery with no residual cognitive or motor deficits 1
• Patients can safely resume long-acting injectable antipsychotic therapy with alternative agents (non-olanzapine formulations) after recovery 1
• The syndrome is self-limited once the acute episode is managed with supportive care 1, 3

Critical Clinical Pearls

• PDSS is specific to olanzapine pamoate LAI: This is not a class effect of all long-acting injectable antipsychotics 4
• Predisposing factors remain unknown: No reliable predictors have been identified to determine which patients are at highest risk 1, 3
• 3-hour observation is non-negotiable: This is the single most important preventive measure and must be implemented for every injection 1, 2
• Distinguish from serotonin syndrome: Patients on SSRIs who receive fentanyl or other serotonergic agents may develop serotonin syndrome, which presents similarly but requires different management 5
• No role for benzodiazepines: Unlike alcohol withdrawal delirium, benzodiazepines should not be used as they worsen sedation and confusion 3