Clozapine reinitiation following a “red result” secondary to chemotherapy
In the next part of this document, we discuss the case of CE, a 58-year-old male with chronic paranoid schizophrenia. Institutional Research Ethics Board approval (PSIY-380-12) and patient consent were obtained for the presentation of the current case. CE had been placed on clozapine after several trials of other antipsychotics in 1998, following a prolonged admission at a chronic care facility. He had been stable from that time onwards with clozapine at 500 mg in divided doses, and was residing at a group home under the care of the local assertive community team (ACT). ACTs are multidisciplinary mental health teams that manage individuals with severe mental illness in the community. They originated in North America in the 1980s as part of the planning to deinstitutionalize the chronic inpatient population and transition them in the community. It is an intense form of support in the community in most places in North America to manage severely mentally ill patients with multiple needs who would otherwise be unable to stay outside tertiary care hospitals. This community mental health team offers support in various domains, like medication compliance, maintenance of accommodation, employment, adhering to probation if required, managing addictions, and offering interventions to improve physical health. At some point, the team was considering discharging him to a step-down service in the community. He developed a swelling in the jaw (4 cm mass in the right preauricular region extending down into the submandibular region) and a right axillary mass (6 cm), which was on examination a lymph-node swelling as noted by the family physician. In addition to this, there were bilateral posterior sternocleidomastoid nodes (measuring 1–2 cm). This prompted a referral to an ear, nose, and throat specialist, who diagnosed him with a large B-cell lymphoma. An emergency referral to the hematologist was set in motion. The lymphoma was graded at clinical stage 3A.\nThis being a treatable form of lymphoma, the hematologist started the CHOP therapy with additional rituximab, now popularly known as the R-CHOP therapy, used for B-cell lymphomas. The plan was set in place for a 21-day cycle with six treatments. The first chemotherapy cycle was well tolerated by the patient, and showed a good response in shrinking of the mass. However, his white cell and neutrophil count went quite low (1.1 and 0.8, respectively) on the 13th day of the cycle, though this was as predicted. The white cell count climbed to 7.0 on the 19th day of the cycle. The local lab alerted the community psychiatrist when CE went for his monitoring blood work. As a consequence of being in the “red zone,” the Clozapine Monitoring Network was promptly informed and a discontinuation protocol initiated.\nThis had an adverse effect on his mental state: he became extremely agitated and restless, and was unable to sleep for days. He was placed on quetiapine in order to manage his psychiatric symptoms. This proved to be inadequate, and he relapsed; his usual relapse signature symptoms of religious delusions exacerbated, and he seemed to be clearly responding to auditory hallucinations. Unfortunately, this meant the hematology team could not give him his second treatment of the R-CHOP cycle. This led to various issues between the ACT service, the hematology team, and the family, who were extremely unhappy with the situation.\nHe ended up in the acute psychiatric unit in view of his psychotic relapse. In an attempt to stabilize him, he was initiated on olanzapine 20 mg in divided doses. Later on, aripiprazole was added to the regimen, which was titrated to 15 mg once daily. He was much calmer and able to sleep, though still tormented by his active psychotic symptoms (ie, religious delusions and auditory hallucinations). The chemotherapy was resumed with the cover of filgrastim (granulocyte colony-stimulating factor) by the heme oncology team.\nAs his psychotic symptoms persisted a decision was made to reinitiate him on clozapine, and the Clozapine Support Network was contacted. The directive given by them was as follows:\nPatient is deemed to be capable of consenting and signs the consent form.\nLetter to be submitted by the prescribing physician outlining the details of the treatment with chemotherapy regimen.\nMonitoring criteria to be set by the prescribing physician in consensus with the hematologist.\nThe consultant hematologist would review the submissions and if in agreement, the patient would be registered with the Novartis Special Program on a compassionate basis.\nThe monitoring service would be informed of the start and end dates of the chemotherapy.\nIf the chemotherapy had ended the regular monitoring protocols would be put in place upon informing the monitoring service.\nThese requirements were fulfilled and the patient was allowed to be reregistered on clozapine. He continued to stay as an inpatient, and received all six cycles of the R-CHOP therapy with filgrastim cover. His white blood cell counts remained within the range of 3.5–11.6, with his neutrophils in the vicinity of 3–5. His lymphoma went onto clinical remission; there was one remaining 2.5 cm right axillary node that was attributed to fibrotic tissue.\nThe patient’s mental state gradually improved with upward titration of clozapine to achieve a suitable therapeutic response at 375 mg daily in divided doses. The achievement of adequate efficacy at a lower dose than previously was attributable to his substantial reduction in smoking while an inpatient. His religious delusions went into the background and the auditory hallucinations lessened in intensity and frequency to a great extent. He was finally discharged to the care of the ACT after being an inpatient for approximately 4 months. The monitoring service was subsequently informed a few months later after review by the cancer (heme oncology) specialists that his treatment for the malignant lymphoma had been completed.