Anemia associated with long-acting injectable aripiprazole in an elderly man

Dear Editor, Aripiprazole, a third-generation antipsychotic with unique receptor binding profiles (partial agonist at the D2 and 5-HT1A receptors and antagonist at the 5-HT2A receptor), is known for having fewer adverse effects (e.g., extrapyramidal syndrome, weight gain, hyperprolactinemia, sedation) compared to other antipsychotics.[1] Long-acting injectable (LAI) antipsychotics are often used to reduce clinical relapses associated with poor adherence to oral medications. While LAI aripiprazole appears to be well tolerated by most patients, hematological adverse effects, including leukopenia, neutropenia, and agranulocytosis, have been reported.[2] Herein, we describe a rare case of anemia potentially associated with LAI aripiprazole in an elderly patient. A 73-year-old hospitalized male with schizophrenia, previously receiving oral aripiprazole (15 mg/day) for more than 2 years, was transitioned to LAI aripiprazole (400 mg, injected every 4 weeks) to improve tolerance and adherence. After 9 months, regular physical examinations revealed a significant decline in hemoglobin levels (13.3 to 5.6 g/dL) despite normal white blood cell (5170/μL) and platelet counts (394,000/μL). Although initial blood transfusion increased the hemoglobin level to 10.3 g/dL, it dropped to 7.6 g/dL within 3 weeks. Comprehensive evaluation, including blood and stool tests, hemoglobin electrophoresis, upper gastrointestinal endoscopy, colonoscopy, and abdominal computed tomography yielded unremarkable results. However, a low reticulocyte count (level: 0.3%, normal range 0.5%–1.5%) was noted in the patient. Considering that LAI aripiprazole was the only recent medication change, it was suspected as the cause of the patient’s anemia. Discontinuation of the LAI resulted in a gradual increase in hemoglobin levels (7.6 to 9.5 g/dL in 2 months and 11.0 g/dl in 3 months) and reticulocyte count (0.3% to 1.9%). Based on the adverse drug reaction probability scale score (Naranjo score) of 5, a “probable” adverse reaction between LAI aripiprazole and anemia was concluded.[3] In this case, the development of anemia following LAI aripiprazole use, coupled with its resolution within recovered in 2–3 months after discontinuation, strongly suggests a diagnosis of LAI-associated anemia. A previous study reported a case of hemolytic anemia associated with oral aripiprazole.[4] To our knowledge, this is likely the first case report of anemia associated with LAI aripiprazole. The precise mechanism underlying LAI aripiprazole- associated anemia remains unclear. Although a significant decline in hemoglobin was observed in our case, the bone marrow’s response to the anemia (reticulocyte count: 0.3%) was inadequate. Following the withdrawal of LAI aripiprazole, the reticulocyte count increased to 1.9%, suggesting that anemia may have been attributed to LAI-induced bone marrow suppression. In conclusion, while LAI aripiprazole-associated anemia is a rare occurrence not explicitly listed as a precaution by the Food and Drug Administration, this case highlights the importance of monitoring hemoglobin levels in these patients, especially if symptoms or signs of anemia are observed. The timely identification of this adverse reaction and discontinuation of the drug can significantly improve patient outcomes. Further research is necessary to elucidate the underlying etiology and pathogenesis of this adverse drug reaction. Informed consent The patient described in the study provided informed consent. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understand that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.