Clozapine reinitiation following a "red result" secondary to chemotherapy

Abstract

We describe a case of a patient whose clozapine was discontinued after a “red result” following R-CHOP (rituximab with cyclophosphamide, hydroxydaunorubicin, Oncovin, and prednisolone) chemotherapy for large B-cell lymphoma. In some cases, manufacturers grant permission, on compassionate grounds, for clozapine to be continued or reinitiated following assessment by their consultant hematologist. Other than a recent case report, there is not much literature surrounding this medical issue. However, since the two leading causes of mortality in schizophrenia are cancer and cardiac disease, this is not an uncommon occurrence. Clinicians are reluctant to prescribe clozapine in view of its side-effect profile, despite its proven efficacy for managing treatment-resistant schizophrenia. The alternative is to prescribe two antipsychotics to manage symptoms. This approach may be associated with increased side effects, and evidence for actual benefits is scant. The consequences were disastrous in this case, as the individual not only relapsed following clozapine discontinuation, but the therapy for this treatable form of lymphoma had to be delayed. He was eventually admitted to an inpatient unit after having been stable for 15 years. We managed to stabilize him with olanzapine and aripiprazole which enabled the heme-oncology group to resume R-CHOP therapy with filgrastim (granulocyte colony-stimulating factor). Even so, he continued to exhibit severe psychotic symptoms, with religious delusions and auditory hallucinations. We therefore applied for permission to rechallenge him on clozapine. Permission was granted when protocol conditions were met, and reinitiation went without any adverse events. The patient’s symptoms showed improvement within a few weeks, and the other antipsychotics were discontinued once clozapine was titrated up to 300 mg. The decision to reinitiate clozapine following a red result is not to be taken lightly, but needs to be considered in terms of the risks versus benefits. More literature surrounding this issue would be of great benefit to clinicians, patients, and their families.

Immunoendocrine Peripheral Effects Induced by Atypical Antipsychotics

“…The risk of neutropenia/agranulocytosis is 0.38% approximately with monitoring and 2.5% without it (79). This was mainly observed in female patients and was directly associated with the time of clozapine use (37,80). Clozapine by itself was not directly toxic to neutrophils or their progenitors at therapeutic concentrations (79).…”

Feasibility of myelosuppressive chemotherapy in psychiatric patients on clozapine: A systematic review of the literature

“…G‐CSF prophylaxis was in this case contraindicated by the patient's primary amyloidosis . Nine cases described the administration of G‐CSF to augment counts . This use represented primary prophylaxis in four cases and secondary prophylaxis in five .…”

“…One report did not specify the age or gender of the patient, 46 and another did not specify age. 31 Nineteen patients had a diagnosis of schizophrenia, 16,18,19,[21][22][23][24][25][26][27][28][29][30]32,34,35,38,41,43 three had schizoaffective disorder, 20,31,40 three had BPD, 37,39,44 one was described only as having "psychosis", 42 and one was without a formal psychiatric diagnosis. 36 The median duration of psychiatric illness was 24.5 years.…”

“…21 Nine cases described the administration of G-CSF to augment counts. 20,25,26,28,30,35,[40][41][42] This use represented primary prophylaxis in four cases 20,26,30,40 and secondary prophylaxis in five. 25,28,35,41,42 Count recovery was described in three cases as being achieved by 3, 20 5 25 and 10 30 days, respectively, with time to recovery not specified in the remaining six.…”

Continuation of clozapine during chemotherapy and a stem cell transplant

“…4,[6][7][8][9][10] Munshi et al 6 report a case of a patient who had been mentally stable for 15 years before developing B-cell lymphoma. As a predictable consequence of the R-CHOP chemotherapy regimen, the patient developed a red result and the community psychiatrist stopped the clozapine.…”