A pooled analysis of injection site-related adverse events in patients with schizophrenia treated with olanzapine long-acting injection

Abstract

BackgroundDepot antipsychotic injections are an important tool for the management of patients with schizophrenia who have difficulty with adherence to oral medication. However, pain and discomfort at the injection site can be a potential impediment to the use of these long-acting formulations. We report here the results of a pooled analysis of injection site-related adverse events (AEs) collected during treatment with the olanzapine long-acting injection (olanzapine LAI).MethodsUnsolicited injection site-related AEs were pooled from 7 olanzapine LAI clinical trials conducted in patients between March 2001 and December 2010. All patients had a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) or Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of schizophrenia or schizoaffective disorder and were between the ages of 18 and 75. Doses ranged from 45 to 405 mg olanzapine LAI, and injection intervals were 2, 3, or 4 weeks. Events were evaluated for severity, timing, possible risk factors, and outcome. A criterion of p < .05 for statistical significance was used for all tests.ResultsA total of 1752 patients received at least 1 olanzapine LAI injection. Of these, 92 patients (5.3%) reported at least 1 injection site-related AE, with “pain” being the most common type (2.9%). Most events were mild (81.4%) and the median duration was 3 days. Four patients (0.2%) discontinued due to injection site-related AEs. Dose volume and body mass index did not appear to affect the probability of injection site-related AEs. However, patients who experienced a post-injection delirium/sedation syndrome event (n = 37) were more likely to have or have had an injection site-related AE at some time during the study. Incidence of injection site-related AEs appeared to decrease over time. In 94.2% of the injection site-related AEs, no specific treatment or concomitant medication was reported; in 9 cases, patients received pharmacologic treatment for reaction, mass, abscess, rash, or pain.ConclusionsInjection site-related AEs with olanzapine LAI were generally mild. The incidence and nature of these injection site-related AEs were generally similar to those occurring during treatment with other injectable antipsychotics.Trial registrationClinicalTrials.gov ID; URL: NCT00094640, NCT00088478, NCT00088491, NCT00088465, and NCT00320489.

Supra-therapeutic plasma concentrations of haloperidol induce moderate inhibition of lipopolysaccharide-induced interleukin-8 release in human monocytes

“…Rare injection site reactions have been reported after intramuscular haloperidol administration (32); however, injection site abscesses after intramuscular injection of haloperidol decanoate appear to be rarer (Haldol ® Injection, Janssen, package inset). The results presented here are consistent with previous observations that severe injection site complications occur infrequently after intramuscular olanzapine (33) or risperidone (34) injections.…”

Does the frequency of administration of long acting injectable antipsychotics impact psychiatric outcomes and adverse effects: A systematic review and meta-analysis

“…However, the sample size for the study comparing monthly versus two-monthly aripiprazole injections were small (n = 35 in each arm) (Risinger et al, 2017). The reasons for this are unclear, as injection site pain does not seem to be dependent on injection volume, dose, or site of administration (Atkins et al, 2014;Kern Sliwa et al, 2018). This may potentially be due to different injection techniques, although there is also the suggestion that the incidence of injection site pain reduces with an increasing number of injections received (Atkins et al, 2014).…”

“…The reasons for this are unclear, as injection site pain does not seem to be dependent on injection volume, dose, or site of administration (Atkins et al, 2014;Kern Sliwa et al, 2018). This may potentially be due to different injection techniques, although there is also the suggestion that the incidence of injection site pain reduces with an increasing number of injections received (Atkins et al, 2014). One explanation might be that patients who were not susceptible to injection site pain tended to stay on the injections longer and so M A N U S C R I P T…”

“…became desensitised to the injections over time (Atkins et al, 2014). Meanwhile, there is limited previous data on the effect of different dosing frequencies on somnolence.…”

Antipsychotics and rashes

“…Rashes due to antipsychotic use that were reported in the literature are summarized in Table 1. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] In the psychiatric setting, rashes are most commonly associated with the mood stabilizer lamotrigine. However, it is important to realize the other skin manifestations after antipsychotic treatments.…”