Abstract
When neutropenia occurs in people taking clozapine, cessation of treatment is mandated and relapse often results. However, neutropenia can arise because of factors unrelated to clozapine treatment. Risks of clozapine rechallenge vary according to the cause of neutropenia. Clozapine may be restarted if non-clozapine causes of neutropenia are identified and eliminated [1,2,3].
We describe a 37 year old single man of Philippine background on disability support pension living with his family. He has a history of schizoaffective disorder spanning the last seventeen years. His treatment was complicated by the development of neuroleptic malignant syndrome (NMS) and neutropenia in response to antipsychotics that represented significant barriers to his future management options.
His illness started soon after migrating to Australia when he was nineteen years old. On initial presentation he exhibited psychosis with catatonic features that responded to haloperidol, but he did not recover. After a few months of non-adherence to treatment he relapsed into a manic episode. During this episode he developed NMS while on a combination of haloperidol and lithium. Subsequently he was switched to clozapine, which led to an improvement in his mental state and daily functioning. His future relapses were mostly precipitated by abrupt discontinuation of clozapine due to a lack of insight. During the treatment with clozapine his white cell count remained normal for nine years.
In 2007 he was diagnosed with systemic tuberculosis affecting his upper lungs, liver and bowel. He received antitubercular treatment with isoniazid, pyrazinamide, rifampicin and ethambutol for nine months while taking clozapine. During this time he developed neutropenia (0.5 × 109/l) and leucopenia (2.7 × 109/l) and clozapine was ceased. This resulted in a psychotic relapse with catatonic features for which he received a course of ECT with a limited response. Maintenance ECT was proposed but was not given. His future management became a therapeutic challenge. Consecutive trials of maintenance treatment with valproate, topiramate, allopurinol, clobazam and lorazepam were unsuccessful in preventing further relapses. In 2010 we initiated a trial of a low dose of quetiapine which was discontinued immediately after he developed NMS. Clozapine remained the only option to treat his psychosis. After a careful re-evaluation of past treatments we noted that the late onset neutropenia occurred due to a combined treatment of clozapine with isoniazid and rifampicin, which are also known to cause neutropenia. Following consultation with a haematologist we cautiously re-commenced our patient on clozapine. The daily dose of clozapine was titrated to 500 mg with twice weekly blood monitoring. He showed a significant improvement in his symptoms and social functioning and his white cell count remained stable.
This case demonstrates the importance of careful consideration of the possible contribution of iatrogenic causes when a patient taking clozapine presents with late-onset neutropenia.