Monocytosis Subsequent to Ziprasidone Treatment: A Possible Side Effect

Sir: Ziprasidone is an atypical antipsychotic agent that is available as oral and short-acting intramuscular formulations and is approved by the U.S. Food and Drug Administration for management of schizophrenia and bipolar disorder. Ziprasidone acts as a serotonin and dopamine receptor antagonist, with greater affinity for the 5-HT_2A receptor than the dopamine D₂ receptor.¹ Moreover, it possesses agonist activity at the serotonin 5-HT_1A receptor.¹ The low affinity of ziprasidone for α-adrenergic, histaminergic, and muscarinic receptors favors a good safety and tolerability profile. Commonly observed side effects are often negligible and include metabolic effects, QTc prolongation, and movement disorders.² Here, we report the case of a schizophrenia patient with monocytosis subsequent to ziprasidone monotherapy.

Case report

Mr. A, a 22-year-old man, was admitted to the hospital in 2006 with a first episode of paranoid schizophrenia (DSM-IV criteria). The patient had no history of psychiatric or neurologic illness. Drug screening, magnetic resonance imaging, lumbar puncture, and routine laboratory testing including blood count, C-reactive protein, and liver enzymes (alanine aminotransferase, aspartate amino-transferase) were unremarkable.

We started therapy with olanzapine 20 mg/day. However, at day 10, routine laboratory testing detected increased liver enzymes, and ultrasound showed hep-atomegaly, so olanzapine treatment was therefore stopped. After termination of medication, Mr. A's liver enzymes normalized promptly, and hepatomegaly resolved during the next 7 days. Subsequent to normalization of diagnostic findings, we started treatment with ziprasidone 160 mg/day. However, the next routine laboratory testing, on day 7 of treatment with ziprasidone 160 mg/day, showed an isolated monocytosis, with a monocyte level of > 1.35 (× 10⁹/L). Laboratory tests at days 14 and 21 of treatment with ziprasidone 160 mg/day confirmed monocytosis. Liver enzyme levels, sonography, C-reactive protein levels, blood cultures, urine culture, urinalysis, electrolyte levels, and chest x-ray were unremarkable, and clinical examination revealed no infection signs. Due to the observations of monocytosis, we initiated a detailed hematologic and hepatologic workup. Alcoholic, viral, immunologic, and cancerous reasons were excluded, and our hematologic and hepatologic consultants diagnosed a medication-induced process.

After 28 days, ziprasidone treatment was stopped, and risperidone treatment was initiated. The next laboratory tests, on day 7 after completion of ziprasidone treatment, detected a declining monocyte level of < 0.85 (× 10⁹/L). Measurements of serum olanzapine and ziprasidone never showed elevated levels.

After exclusion of other symptomatic causes, the close temporal relationship between monocytosis and onset of ziprasidone medication and the disappearance of this condition with termination of therapy with the drug argue against a natural course and support the assumption that monocytosis was induced by ziprasidone. It remains debatable if the observed effect has any clinical relevance or is only a transient phenomenon. However, to our knowledge, ziprasidone-induced monocytosis has not yet been reported.

Moreover, this case again highlights the known and mostly transient phenomenon of liver enzyme increase and hepatomegaly subsequent to olanzapine treatment and demonstrates the importance of regular laboratory tests, including liver enzymes, during medication with atypical antipsychotics.