Paliperidone Induced Neutropenia in First Episode Psychosis: a Case Report Natalie Martos†, William Hall†, Alicia Marhefka, Thomas W
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Martos et al. BMC Psychiatry (2021) 21:76 https://doi.org/10.1186/s12888-021-03073-w CASE REPORT Open Access Paliperidone induced neutropenia in first episode psychosis: a case report Natalie Martos†, William Hall†, Alicia Marhefka, Thomas W. Sedlak and Frederick C. Nucifora Jr* Abstract Background: Neutropenia, a decrease in total number of neutrophils below 1500/mm3 and particularly severe neutropenia, defined as neutrophils less than 500/mm3, is a potential adverse effect of antipsychotic medications that can lead to increased risk of infections and death. However, much of the attention on the potential adverse effect is centered exclusively on clozapine, which remains the only antipsychotic medication in the United States requiring standardized monitoring of blood work. We demonstrate here that paliperidone can also cause neutropenia and therefore clinicians should be aware of this possibility especially during initiation of treatment. Case presentation: The following report presents the case of a 23-year-old African American male with first episode psychosis who developed neutropenia after initiation of paliperidone. Neutropenia resolved after discontinuation of paliperidone and initiation of an alternative antipsychotic, haloperidol. Conclusions: This case report demonstrates an example of paliperidone induced neutropenia which resolved with a switch to haloperidol. We conclude that when initiating paliperidone, clinicians should be more aware of the risk of neutropenia. Moreover, neutropenia may be a more common and overlooked issue in patients on antipsychotic medications other than clozapine and increased awareness of comparative risk across antipsychotics could help direct treatment. Keywords: First episode psychosis, Neutropenia, Paliperidone, Schizophrenia, Clozapine Background with the initiation of the atypical antipsychotic, paliperi- Neutropenia, a decrease in total number of neutrophils done. We later discuss the future implications of neutro- below 1500/mm3, is a potential adverse effect of anti- penia in antipsychotic medications other than clozapine. psychotic medications that can lead to increased risk of infections. However, much of the attention on the po- Case presentation tential for neutropenia and severe neutropenia, defined A 23-year-old African American male with previous high 3 as neutrophils less than 500/mm , is centered exclusively level of social and academic functioning, family history on clozapine, which remains the only antipsychotic of depression, and no past medical or psychiatric history medication in the United States requiring standardized was admitted to an inpatient psychiatric unit for treat- – monitoring of blood work [1 3]. ment of several months of uncharacteristic, odd behavior In the following case report, we describe a relatively and disorganized thought process. On presentation, the treatment-naïve patient with new onset psychosis whose patient could not provide a coherent narrative. His fam- absolute neutrophil count (ANC) dropped significantly ily and friends reported gradual onset of odd behavior within the year prior to admission. These behaviors in- * Correspondence: [email protected] cluded wearing his rugby helmet around his college †Natalie Martos and William Hall contributed equally to this work. Deptments of Psychiatry and Behavioral Sciences, Johns Hopkins University campus, discarding clothes in the trash, and becoming School of Medicine, 600 N. Wolfe Street, Baltimore, MD 21287, USA increasingly disheveled in appearance. 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The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Martos et al. BMC Psychiatry (2021) 21:76 Page 2 of 4 the state, in the middle of the night, to his mother’s initiation of haloperidol, indicating that neutropenia was home to then fearfully claim he was being pursued and most likely related to the initiation of paliperidone. his mother was trying to kill him. We also considered other contributing factors to his Several weeks prior to admission, the patient was hos- neutropenia. He was also treated with clonazepam and pitalized, diagnosed with schizophrenia, and prescribed escitalopram during his course but with no evidence of perphenazine 8 mg twice daily and doxepin 50 mg temporal relationship to his neutropenia. However, there nightly. After 7 days of inpatient care he was discharged. are reports of clonazepam induced neutropenia [4]. His disorganized behavior returned 3 days after dis- Though clonazepam had been discontinued by the time charge, prompting his mother to bring him for inpatient the patient developed neutropenia, we cannot rule out a psychiatric admission. possible synergistic effect from both paliperidone and On presentation, he was responding to internal stim- clonazepam. Additionally, while there are no agreed uli, regularly glancing around the room during the inter- upon risk factors for antipsychotic induced neutropenia view. His speech was latent with intermittent thought (particularly paliperidone-induced), one might reason- blocking. He reported somatic delusions regarding his ably apply risk factors for clozapine induced neutropenia heart and a general delusional atmosphere feeling that to this case. And in this case, neuroleptic naivety, higher everything around him was connected. He reported an doses of neuroleptics, African American race, male gen- auditory hallucination of the devil’s voice. der, and younger age all may have placed him at greater Admission labs (WBC 5300, ANC 2100), urine tox- risk of developing neuroleptic induced neutropenia [5, icity, and head CT were all unremarkable. He was diag- 6]. Furthermore, we considered the role of benign ethnic nosed with schizophrenia and started on aripiprazole 10 neutropenia (BEN); however, hematology consultants mg, which was increased to 20 mg. He was also treated did not consider this a factor given his ANC counts be- with escitalopram 10 mg daily given concern for possible ing consistently greater than 1500 prior to initiation of affective component and clonazepam 0.25 mg twice daily neuroleptics. for anxiety. After nearly 2 weeks, the patient demon- To date, we are only aware of three other case reports strated little improvement on mental status exam. on neutropenia induced by paliperidone. In all three Given lack of response to aripiprazole, he was transi- cases, neutropenia resolved within several days to weeks tioned to oral paliperidone 6 mg. His ANC prior to pali- after discontinuation of paliperidone [7–9]. In one case, peridone initiation was 4120. Following 15 days of lithium was successfully added temporarily to counteract paliperidone 6 mg, he started to respond with improve- the neutropenia [7]. Two of the reports suggested that ment in his psychotic symptoms. However, his complete neutropenia was dose related and concomitant psychi- blood count at day fifteen of paliperidone revealed an atric medications (divalproex sodium and quetiapine in ANC of 1210 with a nadir of 960 (WBC nadir of 3720) one case, risperidone in the other) could have also syner- on serial monitoring. Aside from neutropenia, there gistically contributed to development of neutropenia [7, were no other lab abnormalities. Peripheral smear 8]. In all cases, patients had been on their previous regi- showed mild leucopenia with neutropenia and relative mens without neutropenia prior to initiation of paliperi- lymphocytosis. Antinuclear antibody (ANA) and human done. The patient described here highlights that the immunodeficiency virus (HIV) were both negative. Phys- decrease in ANC may occur at low to middle doses of ical exam was unremarkable. Hematology specialists paliperidone since the Food and Drug Administration concluded that the timeline and negative work-up were FDA maximum dosage is 12 mg and early in the course most consistent with drug-induced neutropenia. Paliper- of treatment. Of note, paliperidone (9-hydroxyrisperi- idone was discontinued after 20 days of treatment and done) is a metabolite of risperidone. A literature review haloperidol 10 mg nightly was started. ANC was moni- demonstrates evidence of risperidone induced blood dys- tored three times weekly. Gradually, his counts improved crasias, including neutropenia [10, 11]. Thus, it stands to and 16 days after discontinuation of paliperidone, reason that risperidone’s metabolite could also lead to returned to normal with an ANC of 2070 (WBC 5220). neutropenia. While on haloperidol, the patient showed progressive Our case report highlights the potential for antipsy- improvement of