NYMC Faculty Publications

Long-Acting Injectable Antipsychotics and the Development of Postinjection Delirium/Sedation Syndrome (PDSS)

Author Type(s)

Faculty

DOI

10.1097/WNF.0b013e3182854f70

Journal Title

Clinical Neuropharmacology

First Page

59

Last Page

62

Document Type

Article

Publication Date

1-1-2013

Department

Neurology

Second Department

Pharmacology

Keywords

Animals, Antipsychotic Agents, Delayed-Action Preparations, Delirium, Humans, Hypnotics and Sedatives, Injections, Intramuscular, Randomized Controlled Trials as Topic, Syndrome

Disciplines

Medicine and Health Sciences

Abstract

OBJECTIVES: Five long-acting injectable (LAI) antipsychotics are currently available in the United States for the treatment of schizophrenia: fluphenazine decanoate, haloperidol decanoate, risperidone microspheres, paliperidone palmitate, and olanzapine pamoate. Additionally, aripiprazole LAI is currently under FDA review. However, research into the safety and tolerability of these LAIs, with particular regard to the development of postinjection delirium/sedation syndrome (PDSS), is limited and has been focused mainly on olanzapine pamoate. This proposal seeks to review data regarding all currently available LAI antipsychotics to determine if a significant association exists between these depot formulations and the development of PDSS.

METHODS: A review of all published literature from 2005 to the present was obtained via a PubMed search for current data regarding the topic of LAIs and the development of PDSS. Keywords used for the search were "long-acting injectable antipsychotics" in association with one of the following: "post-injection delirium/sedation syndrome," "PDSS, " "side effects, " and "tolerability." References to key articles were further explored for relevancy to this proposal.

RESULTS: A case analysis based on all 8 olanzapine LAI clinical trials conducted between August 2000 and October 2008 showed an occurrence of PDSS in approximately 0.07% of injections or 1.4% of patients (30 cases in 29 patients). A second case analysis reviewing the clinical trial databases for 15 completed studies and the postmarketing safety database for risperidone LAI versus 10 completed clinical trials of paliperidone palmitate failed to demonstrate an occurrence of PDSS events in patients receiving either LAI treatment. However, one case of PDSS was identified in a placebo group. In 4 randomized, double-blind, placebo-controlled trials, treatment-emergent adverse events leading to treatment discontinuation were similar for paliperidone palmitate and placebo; however, among the most frequently occurring treatment-emergent adverse events was somnolence/sedation (5%-7% paliperidone palmitate group vs 3% placebo).

CONCLUSIONS: Postinjection delirium/sedation syndrome is a potentially serious adverse event that has been shown to be associated with one currently available LAI antipsychotic, olanzapine pamoate. However, further data are still needed to both support this conclusion and determine if an association exists among other currently available LAIs and PDSS. With the bulk of current evidence coming from registration studies, head-to-head comparison studies between 2 LAIs would help to determine whether the risk of postinjection complications differs among different agents. Further observational studies are also needed to address the incidence, severity, and optimal clinical management of this syndrome.

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