Complications of clozapine cessation in the context of chemotherapy-related neutropenia—a case report

Background Clozapine is the gold standard for treatment-resistant schizophrenia (TRS). It requires strict monitoring of full blood count (FBC), due to the risk of neutropenia and agranulocytosis. Case history AB is a woman in her mid-40s with TRS, diagnosed with invasive ductal carcinoma of the right breast. She was commenced on a chemotherapy regimen of docetaxel, carboplatin, trastuzumab, and pertuzumab. Four days after the initial infusion, AB developed neutropenia with an absolute neutrophil count of 0.2 × 10 9 /L. In accordance with local protocols and discussion with the Clozapine Patient Monitoring Service (CPMS), clozapine was immediately discontinued. Two weeks after clozapine cessation, AB displayed catatonic symptoms characterised by mutism, posturing, and automatic obedience, scoring 27 on the Bush–Francis Catatonia Rating Scale (BFCRS). A positive lorazepam challenge confirmed the diagnosis of clozapine-withdrawal catatonia. Despite regular high-dose benzodiazepines and treatment with antipsychotics, AB’s presentation continued to deteriorate, characterised by prominent delusions and hallucinations, impeding oncological treatment. AB was seen extensively by liaison psychiatry and treated with high-dose typical and atypical antipsychotics; however, she failed to respond adequately to treatment. Given AB’s extensive previous history of management on clozapine without previous haematological disturbance and ongoing decline in mental state, coupled with the timeline of symptoms 4 days after the administration of chemotherapy agents associated with neutropenia, namely, carboplatin, the decision was taken to reinstate clozapine. Following titration of clozapine and transfer to a specialist psychiatric unit, AB’s symptoms resolved rapidly, allowing for the successful completion of chemotherapy. Carboplatin was omitted in subsequent cycles, with no further episodes of neutropenia. Discussion This case highlights the diagnostic challenge of neutropenia in psychiatric patients on clozapine, who are also undergoing treatment for comorbid medical conditions. The presence of neutropenia in clozapine patients may lead to diagnostic overshadowing and delay the diagnosis of the underlying cause of neutropenia, resulting in delays to treatment as well as unnecessary cessation of clozapine and risk of relapse. Furthermore, this case highlights the risk of catatonia associated with the withdrawal of clozapine and the importance of its rapid identification and management. Conclusions Clinicians should consider differing aetiologies of neutropenia in clozapine patients, especially those undergoing chemotherapy. Furthermore, clinicians should be skilled in recognising catatonia and initiating prompt treatment.