Neutropenia in Incarcerated Adolescents Secondary to Intranasal Quetiapine Misuse

Introduction

Between April 2015 and May 2016, six young males incarcerated at a Youth Justice center were identified as having unexplained neutropenia. These young people had blood counts performed for health screening, or metabolic monitoring for other prescribed psychotropic medications (Table 1). None of the young people with neutropenia were prescribed quetiapine (or clozapine or olanzapine). Indications for prescription of quetiapine in young people aged 14–19 years were schizophrenia and bipolar disorder.

During the assessment of these neutropenic young people, it was noted that there had been an administrative decision across all Youth Justice centers in the state for quetiapine tablets to be administered in a crushed form to address problematic diversion. This particular center had no after-hours nursing staff, and the quetiapine powder was administered after hours by nonhealth/custodial staff. The child and adolescent psychiatrist prescriber of quetiapine was not involved in these administrative decisions.

During this time period, all of the neutropenic young people appeared well when assessed, and there were no electrocardiogram abnormalities (normal rate and rhythm, electrocardiograph corrected QT intervals <440 ms; Van Dorn et al. 2011). All of the young people were questioned, counseled and underwent a full medical assessment. Two of these young people admitted to “snorting” diverted quetiapine powder. For those cases remaining in the center at follow-up, the neutropenia resolved once the medication was removed from the center.

Discussion

Quetiapine is a popular second-generation antipsychotic with increasing off label use in anxiety and insomnia (Chiappini and Schifano 2018). Postmarketing surveillance reports from the United States show an increase in black marketing of quetiapine since 2001, and a 90% increase in emergency department presentations secondary to quetiapine misuse (Klein et al. 2017), making it the most abused second-generation antipsychotic. Quetiapine was recently listed as a Schedule 4D restricted substance in Australia by the Poisons and Therapeutic Goods Regulator due to its potential for abuse, misuse, and trafficking (Therapeutic Goods Administration, April 2020). Quetiapine misuse in the opiate using community and the custodial setting is well documented, where “Qwell” or “Baby Heroin” is sought after for its anxiolytic and sedative properties (Pierre et al. 2004; Kim et al. 2017).

“Pulverizing” quetiapine tablets by crushing permits a range of alternative routes for abuse that include intranasal, smoking and intravenous, and was first described in 2004 among inmates of the Los Angeles County Jail (Pierre et al. 2004). Such misuse can result in serious morbidity and mortality through central nervous system, cardiac, respiratory, and hematological adverse events. Crushing a medicine may alter its stability, and change how it is absorbed, potentially resulting in increased toxicity. Crushing or dispersing a medicine is an option of last resort, and may not always be appropriate (Australian “Don't Rush to Crush” Handbook, 3rd ed. 2010). Analysis of the U.S. National Poison Data System shows that toxicity secondary to quetiapine misuse was more common in adolescents presenting to emergency departments as compared with adults (Klein et al. 2017), with moderate to major toxicity occurring in 1 in 4 cases (drowsiness, confusion, delirium, agitation, respiratory depression, and seizures being most common).

Neutropenia is a less obvious side effect, and occurs rarely in controlled studies, with a frequency of 0.01% (compared with up to 10% of patients taking clozapine, with which it shares a similar chemical structure). Quetiapine-induced neutropenia is not well understood, with possible causes being toxicity, bone marrow suppression, or antibody mediation. Neutropenia and agranulocytosis have a variable onset from between 1 week to 1 year, and are independent of the dose (Australian Prescriber 2008).

Conclusions

This case series describes a number of incarcerated youth who simultaneously developed neutropenia during a 12-month period of quetiapine availability at a Youth Justice center, very likely through intranasal misuse (although direct causality cannot be established as several of the young people did not disclose intranasal abuse). Several isolated cases of intranasal quetiapine toxicity have been reported previously, but this is the first article to describe a neutropenic cluster from intranasal misuse of quetiapine (Morin 2007; Reeves and Brister 2007). When taken correctly as prescribed, quetiapine-induced neutropenia is a rarely reported side effect; however, this study suggests that it is much more common in young people in the context of misuse.

Clinical Significance