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PRUETTE ET AL.
watch with more vigilant monitoring and intervention
from staff. A national survey of U.S. prisons found that
85% of systems experienced episodes of SIB at least
weekly in 2008 (Appelbaum et al., 2011).
Traditionally, prisons have managed the behaviors associated
with treatment-refractory schizophrenia or severe
personality disorders with tighter control and enforcement
of regulations, potentially including use of seclusion or restraints,
though more likely restrictive housing. These
methods may exacerbate issues for some people with severe
mental illness and paradoxically increase the behaviors
that they are meant to curtail (Andersen et al., 2000).
Benefits of Clozapine Treatment
The antipsychotic medication clozapine, available for over
30 years in the United States, is the only medication approved
by the Food and Drug Administration for treatmentrefractory
schizophrenia and reduction in suicidal behavior
in schizophrenia or schizoaffective disorder. It is available
as a low-cost generic drug. Multiple studies have shown
clozapine tobe superior toother antipsychotics in treatmentrefractory
psychotic patients and to be a cost-effective treatment
(Kane et al., 1988; Velligan et al., 2015).
In addition, when compared to other antipsychotics,
clozapine has the lowest risk of death from any cause,
largely driven by a significant reduction in suicides (Tiihonen
et al., 2009). In the community, clozapine has been
associated with substantial reductions in SIBs as well in
patients with either a psychotic disorder or personality
disorder (Rohde et al., 2018; Wimberley et al., 2017; Zarzar
& McEvoy, 2013). Typically, about 40% of patients
with treatment-refractory schizophrenia benefit from clozapine
(Siskind et al., 2017).
Data on clozapine use in prisons have been limited to
date. Balbuena et al. (2010) found improved institutional
adjustment and fewer infractions among patients treated
with clozapine compared to other antipsychotics. In a
study of patients receiving antipsychotics conducted
after their release from correctional facilities, patients
on clozapine had more crime-free time in the community
and a longer time to first offense when compared to those
on other antipsychotics (Mela & Depiang, 2016).
In North Carolina, a small cohort of treatmentrefractory
patients with severe personality disorders and
repetitive self-injury had substantial reductions in SIB,
disciplinary infractions, and assaults on custody staff
with clozapine therapy (Zarzar et al., 2019). A followup
study confirmed reductions in self-injurious episodes
and days on suicide watch in both psychotic and
personality-disordered patients (Zarzar et al., 2022).
Lastly, a broader cohort of all clozapine-treated patients
over a 3.5-year period experienced significant reductions
in disciplinary infractions and time assigned to restrictive
housing (disciplinary segregation) after clozapine treatment
compared to before treatment (Zarzar et al., 2021).
Underutilization of Clozapine
Despite its benefits, clozapine is widely underused in the
community (and even more so in corrections) for an array
of reasons. Rates of clozapine use in the community are
typically less than 10% of eligible patients (Stroup
et al., 2014). The primary barrier is a requirement for
weekly blood monitoring upon initiation related to an approximately
1% risk of white blood cell count reduction
(neutropenia; Alvir et al., 1993; Kelly et al., 2018; Love
et al., 2016). Transportation to a laboratory and payment
for services can be additional burdens.
In addition, clozapine prescribers, pharmacies, and patients
must be registered in the Clozapine Risk Evaluation
and Mitigation Strategy (REMS) system, and lab
test values must be communicated between the laboratory,
prescriber, and pharmacist. There also are several
rare but significant side effects that must be assessed
for and managed including myocarditis and colitis. The
initiation process is also more complex and significantly
more time consuming for clozapine than other antipsychotic
medications and requires more medical monitoring
early in treatment. The rate of dosage titration of
clozapine is based on an individual's ability to tolerate
the less serious side effects such as sedation and orthostatic
hypotension.
The greater time and logistic challenges that come
with prescribing clozapine are not afforded extra reimbursement
in the community, a major rate-limiting step
to broadening its use (Kelly et al., 2018). Upon prison release,
it can be a challenge to find a community clozapine
prescriber and to ensure timely follow-up for blood
draws.
In addition to these community barriers, prison systems
have unique difficulties. In prisons, up to onethird
of states report clozapine is not on their formularies
(Sheitman et al., 2019). Although there is limited systematic
investigation into the available psychiatric or mental
health staffing in prisons, a recent review highlighted the
paucity of dedicated mental health units in correctional
systems (Cohen et al., 2020). Patients are frequently
transferred between prisons or move locations within
prisons, making them more difficult to consistently monitor
and track. Despite these hurdles, state prisons are
closed systems that can be leveraged to bring together
various departments including pharmacy, nursing, medicine,
laboratory, and mental health to provide a clear protocol
for prescribing and monitoring clozapine.
Increasing Clozapine Use in North
Carolina Prisons
In 2014, the North Carolina Department of Public Safety
(NC DPS) entered a partnership with the University of
North Carolina (UNC) School of Medicine Department
of Psychiatry to provide contract in-person and telehealth
Journal of Correctional Health Care - April 2023

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