The COVID-19 pandemic has posed considerable challenges in providing care for persons
with schizophrenia. The ambulatory clinic of Comprehensive Recovery Service Line of
the UPMC-Western Psychiatric Hospital serves around 1500 patients, nearly 1200 with
psychotic disorders. When the COVID-19 National State of Emergency was declared (March
13th, 2020), safety precautions including social distancing efforts were rapidly implemented
in our clinics on March 16 to prevent contagion-based transmission of the virus. While
most visits were quickly converted to telehealth, the clozapine clinic and long acting
antipsychotic injections necessitate in person encounters and are paramount for ensuring
patient stability.
Undeniably, clozapine is the best treatment for refractory schizophrenia, yet it remains
significantly underutilized (Sarpal et al., 2019). Clozapine is associated with significantly
better clinical outcomes compared to other antipsychotic medications, including fewer
hospitalizations and improved social and community integration (Masuda et al., 2019).
Of note, clozapine is the only medication in the USA dispensed with a “no blood, no
drug” FDA mandate under the Clozapine Risk Evaluation and Mitigation Strategy (Clozapine
REMS), requiring regular absolute neutrophil count (ANC) reporting. The rationale
for this mandate is that clozapine is associated with a low prevalence yet potentially
fatal risk of agranulocytosis. Under normal circumstances, hematologic monitoring
decreases from every week after 6 months to every two weeks until one year, and then
to every 4 weeks. Unless the regularly scheduled ANC is verified to be within a specified
reference range, the pharmacists cannot dispense clozapine to the patient.
Our clozapine clinic serves 184 patients; the majority (n = 165, 90%) are on monthly,
nine on biweekly, and ten are on weekly ANC monitoring schedules. Under the care of
several attending psychiatrists, in our clozapine clinic model, patients first see
a phlebotomist, then have a structured visit with a nurse well versed in long-term
clozapine management and receive clozapine at the adjoining pharmacy, if the ANC is
verified by the pharmacist to be in the specified range. This integrated and efficient
clozapine service has operated for 30 years.
As information regarding COVID-19 transmission, morbidity and mortality rapidly emerged,
we responded assertively and effectively to reassure concerned patients and their
caregivers about our safety procedures. We changed clinic workflows to stagger appointments.
Screening for COVID-19 symptoms, social distancing, and the use of personal protective
equipment (PPE) have been previously detailed (Gannon et al., 2020). A plexiglass
shield was added at the pharmacy counter, and pharmacy staff began to increasingly
mail clozapine to patients or provide curbside pick-up to minimize contagion risks.
As the pandemic progressed, on 3/22/2020, the FDA issued guidance that prescribers
may use clinical judgement on whether the benefits of deferring laboratory monitoring
(ANC) outweighs the risk of continuing clozapine treatment without an updated ANC.
Given ANC exemptions, during the first week of April 2020 (Fig. 1
), we permitted patients receiving clozapine for ≥1 year with normal ANCs and with
no signs of infection to switch to telepsychiatry nurse visits; at the discretion
of the attending physician, monthly ANC requirements were also relaxed upto every
3 months, consistent with a recent expert consensus statement (Siskind et al., 2020).
Fig. 1
Fig. 1
The figure (bars) depicts rates of attendance at the clozapine clinic both before
physical distancing measures, and during the pandemic, shown in 2-week intervals.
Not unexpectedly, there was a significant shift from in person nursing visits to telepsychiatry
nursing visits beginning the first week of April 2020 accompanied by a 23.5% drop
in total nursing visits. Older patients were reticent to attend in person visits.
Nurse visits comprise taking vitals, completing a mental status checklist, and monitoring
clozapine side-effects, though vitals could not be completed via telepsychiatry. In
view of the severe respiratory illnesses described with COVID-19 (Guan et al., 2020),
in addition to fever, cough and shortness of breath, we were vigilant about clozapine-induced
sialorrhea, sedation and aspiration which in turn can lead to pneumonia (de Leon et
al., 2020). Whereas 13 patients (7%) had clozapine mailed to them prior to March 16,
2020, once the COVID-19 restrictions were in place, 51 patients (28%) had clozapine
either mailed to them (n = 49) or picked up curbside (n = 2) (black stippled line
in Fig. 1). Starting in early April through May 15, 2020, fifty patients (27%) had
ANC monitoring exempted. At the time of writing (May 18, 2020), no clinical decompensation
among our clozapine treated patients has occurred, and so far, only one patient has
had a treatment gap for delayed pick-up of clozapine.
What factors might account for our capacity to provide continued clozapine clinic
services during the pandemic? First, thus far, the Pittsburgh region has not seen
a surge of viral transmission. Second, and importantly, the long-established clozapine
clinic and collocated pharmacy, with its low turnover of nursing and pharmacy staff,
have built trusting relationships with patients, caregivers and psychiatrists. Additional
factors may include rapid implementation of physical distancing, the use of PPE, mailing
of clozapine, and finally, the rapid deployment of telepsychiatry nursing visits following
authorization of ANC exemptions. Even though a small number of clozapine treated patients
are served by our mobile medication nursing and Assertive Community Teams (ACT), these
teams could not possibly provide in home support to all 184 patients attending our
clozapine clinic. Moreover, we have not yet adopted the Point-of-Care ANC testing
which might better support in home clozapine services.
Data emerging from the COVID-19 pandemic could inform future examples of ANC exemptions,
such as prolonged inclement weather, natural disasters, vacations, etc., and potentially
even address whether long-term ANC monitoring could be safely reduced to less than
every 4 weeks. Clozapine-associated severe neutropenia and mortality is negligible
after one year (Myles et al., 2018). Nevertheless, in the context of the ongoing COVID-19
pandemic, the benefits of relaxing ANC monitoring must be weighed against the possibility
that febrile neutropenia, pneumonia including acute respiratory distress syndrome
and mortality could be associated with either clozapine treatment (de Leon et al.,
2020) or viral infections including SARS-CoV-2 (Guan et al., 2020) or both.
Sponsorship and sources of funding
None.
Declaration of competing interest
None of the authors has any conflicts of interest with reference to this article.