Risperidone/paliperidone induced neutropenia and lymphopenia

To the Editor

Risperidone and its primary active metabolite paliperidone are atypical antipsychotic medications used for the treatment of schizophrenia.

Blood dyscrasias such as neutropenia and lymphopenia can increase susceptibility to serious infection. Neutropenia is occasionally associated with the use of antipsychotics but the monitoring of white blood cell (WBC) counts is not routine with the exception of patients using clozapine. The product information for risperidone includes a precaution for neutropenia (MIMS Australia, 2011). Lymphopenia in patients treated with antipsychotic drugs is less well described, published in only a few case reports (Qureshi and Rubin, 2008; Kim et al., 2010).

We report a case in which a patient with pre-existing neutropenia twice developed neutropenia and lymphopenia when treated with combination risperidone and paliperidone.

A 45-year-old gentleman with schizophrenia, alcohol dependence (both DSM-IV-TR criteria) and hepatitis C cirrhosis was admitted to our health service with worsening command hallucinations. He had previously responded well to risperidone without significant change in haematological parameters but had become non-adherent to an oral dose of 2mg at night. Monthly paliperidone palmitate depot injection (100mg) had been recently started under the care of an adjoining health district.

The patient’s WBC count demonstrated neutropenia (0.94x10⁹/L reference range: 2.00- 8.00x10⁹/L) and lymphopenia (0.78x10⁹/L reference range: 1.00-4.00x10⁹/L). He was without physical signs of infection. Historical neutropenia (1.50-1.90x10⁹/L) pre-dating antipsychotic treatment, suggested a non-drug aetiology of his cytopenia. Hepatitis C, cirrhosis and splenomegaly were postulated causes. Oral risperidone 2mg at night was recommenced with rapid improvement in his psychotic symptoms with a view to increasing the depot dose and eventually ceasing oral medication. Oral paliperidone was unavailable for prescription due to local restrictions.

Unfortunately, subsequent laboratory results showed persistent decline in neutrophil (0.72x10⁹/L) and lymphocyte (0.75x10⁹/L) counts over 29 days. Antipsychotic-induced blood dyscrasia was suspected and risperidone was ceased. The patient had rapid improvement in his WBC counts, with lymphopenia resolving above 1.07x10⁹/L and neutropenia stabilising above 1.20x10⁹/L within 3 days. Paliperidone depot injections were discontinued. Fortnightly zuclopenthixol decanoate depot injection (200mg) was used for successful control of psychotic symptoms without further haematological aberration.

Review of the patient’s clinical records outside our health district confirmed the development of significant neutropenia (1.00x10⁹/L) and lymphopenia (0.72x10⁹/L) during a prior episode of treatment with combination depot paliperidone and oral risperidone.

Proposed mechanisms of antipsychotic-induced blood dyscrasia include direct bone marrow suppression, antibody formation against haematologic precursors and peripheral WBC destruction (Flanagan and Dunk, 2008). It has been suggested that most drug induced neutropenia is dose related (Flanagan and Dunk, 2008). This may explain why our patient tolerated single drug therapy with risperidone but repeatedly became cytopenic when given combination risperidone/depot paliperidone.

Whilst this patient had co-morbidities that placed him at risk of developing a blood dyscrasia, these are by no means rare among our patients. This case reminds us of the risk of co-prescribing different antipsychotic formulations and the importance of monitoring the WBC count when starting antipsychotic medication, especially in people with pre-existing leucopenia or a history of drug induced neutropenia/lymphopenia.