A case of iloperidone overdose in a 27-year-old man with cocaine abuse

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Abstract

Introduction:

Iloperidone is a recently introduced antipsychotic medication. It is approved for the treatment of schizophrenia. There are no published reports of iloperidone overdosage, but there are eight cases that have been reported to the US Food and Drug Administration.

Case report:

A case of a 27-year-old man who took 84 mg of iloperidone while also smoking cocaine is described. He developed a prolonged QTc (527 ms) without arrhythmias and respiratory failure with mandated respiratory support. He ultimately recovered without sequelae.

Discussion:

The information regarding previous cases of toxicity on the US Food and Drug Administration website is incomplete. However, there were no fatalities due to iloperidone over-ingestion. Prolongation of the QTc may be a common feature.

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Most cited references 5

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QTc interval prolongation and torsade de pointes associated with second-generation antipsychotics and antidepressants: a comprehensive review.

Mehrul Hasnain, W Victor R Vieweg (2014)

We comprehensively reviewed published literature to determine whether it supported the link between corrected QT (QTc) interval prolongation and torsade de pointes (TdP) for the 11 second-generation antipsychotics and seven second-generation antidepressants commonly implicated in these complications. Using PubMed and EMBASE, we identified four thorough QT studies (one each for iloperidone, ziprasidone, citalopram, and escitalopram), 40 studies specifically designed to assess QTc interval prolongation or TdP, 58 publications based on data from efficacy and safety trials, 18 toxicology studies, and 102 case reports. Thorough QT studies, QTc prolongation-specific studies, and studies based on efficacy and safety trials did not link drug-associated QTc interval prolongation with TdP. They only showed that the drugs reviewed caused varying degrees of QTc interval prolongation, and even that information was not clear and consistent enough to stratify individual drugs for this risk. The few toxicology studies provided valuable information but their findings are pertinent only to situations of drug overdose. Case reports were most informative about the drug-QTc interval prolongation-TdP link. At least one additional well established risk factor for QTc prolongation was present in 92.2 % of case reports. Of the 28 cases of TdP, six (21.4 %) experienced it with QTc interval <500 ms; 75 % of TdP cases occurred at therapeutic doses. There is little evidence that drug-associated QTc interval prolongation by itself is sufficient to predict TdP. Future research needs to improve its precision and broaden its scope to better understand the factors that facilitate or attenuate progression of drug-associated QTc interval prolongation to TdP.

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A thorough QTc study of 3 doses of iloperidone including metabolic inhibition via CYP2D6 and/or CYP3A4 and a comparison to quetiapine and ziprasidone.

Steven Potkin, Sheldon Preskorn, Marla Hochfeld … (2013)

The potential for iloperidone, a D2/5-HT2A antipsychotic, to affect the heart rate-corrected QT interval (QTc) was assessed in the absence and presence of metabolic inhibitors in a randomized, open-label, multicenter study. QT interval prolongation by medications, including both conventional and atypical antipsychotic drugs, can predispose patients to cardiac arrhythmias and result in sudden death. Adults with schizophrenia or schizoaffective disorder and normal electrocardiograms at baseline (N = 188) were randomized 1:1:1:1:1 to iloperidone, 8 mg twice daily (BID), 12 mg BID, 24 mg once daily (QD); quetiapine, 375 mg BID; or ziprasidone, 80 mg BID during period 1 (no metabolic inhibitors present). Iloperidone BID produced mean changes in QTc Fridericia correction (QTcF) interval (8.5-9.0 milliseconds [ms]) similar to those produced by ziprasidone (9.6 ms) and higher than those produced by quetiapine (1.3 ms). Iloperidone, 24 mg QD, produced a mean QTcF change of 15.4 ms. Coadministration of metabolic inhibitors with iloperidone during periods 2 (paroxetine) and 3 (paroxetine and ketoconazole) resulted in greater increases in the QTc interval. Increased QTc was observed in individuals with specific cytochrome P450 2D6 polymorphisms. Up to 10% of patients on iloperidone experienced QTc intervals of 60 ms or longer in the presence of metabolic inhibition and QD dosing. However, no patients experienced QTc changes of clinical concern (QTc ≥ 500 ms). The most common adverse events with iloperidone were headache, anxiety, and dyspepsia. The only cardiovascular adverse events with iloperidone were non-concentration-dependent tachycardia that was mild in most patients and did not lead to further sequelae. Pharmacogenetics and recommendations are discussed.

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The effects of cocaine and heroin use on intubation rates and hospital utilization in patients with acute asthma exacerbations.

Michael Levine, D Ansell, M. Iliescu … (2005)

The use of both heroin and cocaine has been associated with asthma exacerbations. However, the magnitude of this effect has not been adequately described. The purpose of this study was to examine the association between cocaine or heroin use and asthma severity. We conducted a retrospective chart review of adult patients who had been admitted to an inner-city hospital and who subsequently had received a hospital discharge diagnosis of acute asthma exacerbation. Patients were classified as cocaine users if they had admitted to using cocaine within 24 h of symptom onset, or if a positive drug screen result was obtained. A similar classification was employed for heroin. The severity of asthma exacerbations among cocaine and heroin users was compared to severity among nonusers (ie, individuals without evidence of having used either drug within the 24 h preceding symptom onset). One hundred sixty-six unique patient encounters were identified, and 152 patient records were analyzed. Of these, 27.6% (42 of 152 patients) used cocaine with or without heroin and were classified as cocaine users, while 30.9% (47 of 152 patients) used heroin with or without cocaine and were classified as heroin users. Cocaine users had longer mean lengths of hospital stay than nonusers (3.4 days vs 2.5 days; p < 0.049). Intubation and ICU admission were more common among cocaine users than nonusers (21.4% vs 2.3%, respectively [p = 0.0006]; 31.0% vs 11.5%, respectively [p = 0.0068]). Heroin users were also intubated more frequently than nonusers (17.0% vs 2.3%, respectively; p = 0.0036). Neither the length of hospital stay nor the percentage of ICU admissions was significantly different between heroin users and nonusers. Heroin and cocaine use are common among adult asthmatic patients admitted to an inner-city hospital. Both cocaine and heroin are significantly associated with the need for intubation. Based on these findings, it may be prudent to screen adults with asthma presenting to an urban emergency department for cocaine and heroin use.

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Author and article information

Journal

Journal ID (nlm-ta): SAGE Open Med Case Rep

Journal ID (iso-abbrev): SAGE Open Med Case Rep

Journal ID (publisher-id): SCO

Journal ID (hwp): spsco

Title: SAGE Open Medical Case Reports

Publisher: SAGE Publications (Sage UK: London, England )

ISSN (Electronic): 2050-313X

Publication date (Electronic): 08 August 2016

Publication date Collection: 2016

Volume: 4

Electronic Location Identifier: 2050313X16660485

Affiliations

[1-2050313X16660485]Mood Disorders Research Program, Department of Psychiatry and Behavioral Sciences, School of Medicine, University of Louisville, Louisville, KY, USA

Author notes

[*]Rif S El-Mallakh, Mood Disorders Research Program, Department of Psychiatry and Behavioral Sciences, School of Medicine, University of Louisville, Louisville, KY 40202, USA. Email: rselma01@ 123456louisville.edu

Article

Publisher ID: 10.1177_2050313X16660485

DOI: 10.1177/2050313X16660485

PMC ID: 4984480

SO-VID: dc0831be-77ed-4b07-8071-e58423db4fb2

License:

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License ( http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page( https://us.sagepub.com/en-us/nam/open-access-at-sage).

History

Date received : 21 March 2016

Date accepted : 27 June 2016

Custom metadata

cover-date January-December 2016

Keywords: iloperidone,qt,qtc,overdosage,toxicity

Data availability:

Keywords: iloperidone, qt, qtc, overdosage, toxicity

A case of iloperidone overdose in a 27-year-old man with cocaine abuse

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Abstract

Introduction:

Case report:

Discussion:

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Most cited references 5

QTc interval prolongation and torsade de pointes associated with second-generation antipsychotics and antidepressants: a comprehensive review.

A thorough QTc study of 3 doses of iloperidone including metabolic inhibition via CYP2D6 and/or CYP3A4 and a comparison to quetiapine and ziprasidone.

The effects of cocaine and heroin use on intubation rates and hospital utilization in patients with acute asthma exacerbations.

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