Late-onset neutropenia due to clozapine.

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Sir, Clozapine is an antipsychotic drug effective against treatment-resistant schizophrenia. Compared with the classic neuroleptic drugs, clozapine carries a lower risk of extrapyramidal side effects.[1] Despite these advantages, clozapine-induced neutropenia and agranulocytosis can occur with a cumulative incidence of 2.7% and 0.73%, respectively.[2] Although the risk of blood dyscrasias is the highest during the first 6–18 weeks;[3] hence, this side effect can occur even after ≥5 years of treatment with clozapine.[4] Here, we report the case of a 46-year-old woman who developed neutropenia due to clozapine after 8 years of treatment. A 46-year-old woman with a history of schizophrenia since 2004 was treated with therapeutic doses of risperidone for the first 6 months after diagnosis. Because of the lack of improvement in her clinical status, risperidone was replaced by clozapine at an initial dose of 25 mg/day in December 2004; this dose was slowly titrated up to 300 mg/day. Because of her alterations in electroencephalography patterns, valproate 500 mg/day was added in May 2005. Sertraline 100 mg/day was initiated in September 2007 to treat depressive symptoms, and was discontinued in June 2008 because of the clinical improvement. Between 2004 and 2011, the results of hematological monthly monitoring were normal. Although the white blood cell (WBC) count was 6500/mm3 with an absolute neutrophil count (ANC) of 5100/mm3 in December 2011, it declined to 4100/mm3 and 3800/mm3, respectively, over 2 months (ANC was 3170/mm3 and 2660/mm3, respectively). In March 2012, her WBC count had dropped to 2100/mm3 with an ANC of 1280/mm3; however, there were no signs of infection. Laboratory tests and hematological consultations ruled out infectious diseases that could cause neutropenia. The results of her physical examination were unremarkable. After the diagnosis of neutropenia was made, all medications were discontinued, and blood counts were measured weekly. The WBC count reached the normal limit (WBC: 6300/mm3) within 3 weeks after the discontinuation of her medications. Since then, the patient's mental status has been stable with pharmacotherapy, including sertindole 16 mg/day and amisulpride 800 mg/day. Her clinical status remains good, without any recurrence of adverse hematological events. Neutropenia, in this case, could have been due to either clozapine or valproate or a combination of both. A case report described a patient who developed late-onset neutropenia because of sodium valproate; however, the drop in WBC counts emerged after dose escalation in this case.[5] To the best of our knowledge, delayed-onset neutropenia due to a stable dose of valproate has not yet been reported, although it has been observed in the association with a stable dose of clozapine, even after several years.[4] We cannot be certain drugs that caused by the side effect, because of both the drugs were discontinued at the same time, we believe that the neutropenia was most likely to be caused by clozapine. Our case report underscores the importance of regular blood monitoring in patients treated with clozapine. Clinicians should also be aware of other psychotropic medications that can impose the risk of blood dyscrasias. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.