Summary

• No cases of post-injection delirium/sedation syndrome (PDSS) were observed in patients who received RISPERDAL CONSTA in an evaluation that used an algorithm to identify reports of PDSS in data from 15 completed clinical trials (a total of 3,164 patients and 115,000 injections) and the post-marketing safety database.¹

BACKGROUND

During clinical trials for one long-acting injectable antipsychotic, there were reports of a syndrome referred to as PDSS (McDonnell et al, 2008²; Citrome 2009³). The syndrome, while not clearly defined, included symptoms of sedation, dizziness, confusion, slurred speech, altered gait, weakness, or unconsciousness that occur typically within a few hours following the intramuscular injection. The mechanism for PDSS may be related to the solubility of the long-acting injectable antipsychotic formulation in blood or plasma. It has been suggested that PDSS may occur when a long-acting injectable antipsychotic is highly soluble and there is contact with blood from partial injection into the vasculature, vessel injury during IM administration, or substantial bleeding at the injection site. It is unclear if this syndrome is a side effect that can be expected with the use of other long-acting injectable antipsychotics.

CLINICAL STUDIES

Alphs et al (2011)¹ evaluated the incidence of PDSS with paliperidone palmitate and RISPERDAL CONSTA. Data from 15 completed clinical trials (a total of 3,164 patients and 115,000 injections) and the post-marketing safety database were used in the RISPERDAL CONSTA analysis.

The investigators created an algorithm to identify PDSS according to the approximated methods and terms used in reports of PDSS with another long-acting injectable antipsychotic.

• Step 1: The algorithm first identified patients who experienced sedation/somnolence events (SSE) of interest (sedation, somnolence, hypersomnia, lethargy, narcolepsy, or sudden onset of sleep at any time).
• Step 2: The search was then limited to those patients who experienced ≥1 severe SSE within one day of receiving injections.
• Step 3: Next, the search was further limited to those patients who also experienced ≥1 excessive SSE within one day of the injection linked to the severe SSE. The following were considered to be excessive SSEs: cataplexy, coma, fluctuating consciousness, depressed level of consciousness, loss of consciousness, sopor, stupor, unresponsiveness to stimuli, any preferred term under the MedDRA term seizures, any term within the standardized MedDRA query (SMQ) of extrapyramidal syndrome, gait disturbance, gait deviation, parkinsonian gait, tachycardia, sinus tachycardia, hypotension, orthostatic hypotension, diastolic hypotension, or any term within the SMQ of torsades de pointes.
• Step 4: Finally, a manual review of the cases identified from the algorithm was conducted.

This review was limited to those patients who were hospitalized or in whom hospitalization was prolonged due to the sedation/somnolence event.

No cases of PDSS in patients receiving RISPERDAL CONSTA were identified with the algorithm.

LITERATURE SEARCH

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 09 February 2024.

If you would like information about RISPERDAL CONSTA and a particular symptom associated with PDSS, please call the Medical Information Center at 1-800-JANSSEN (1-800-526-7736).