Examining a Case of Psychiatric Polypharmacy-Related Agranulocytosis

Darwin Brandis_AdobeStock

A recent study examined the association between psychiatric polypharmacy and agranulocytosis, with a particular emphasis on the potential risks and adverse effects of polypharmacy in patients with complex psychiatric conditions. The study’s investigators explored this association through a case study of a 20-year-old female with a history of multiple psychiatric conditions.¹

The patient, who had been residing in a psychiatric facility, presented to the hospital with weakness, dizziness, myalgia, and fever, prompting evaluation for medication management. Her extensive psychiatric history included major depressive disorder, borderline personality disorder, posttraumatic stress disorder, anxiety disorder, and a history of suicide attempts. She also had a medical history of ulcerative colitis and hypothyroidism.¹

The patient’s treatment regimen consisted of multiple psychiatric medications, including chlorpromazine, topiramate, lamotrigine, lithium, bupropion, and citalopram. In addition, clozapine had been added to her regimen 1 month before her admission to the hospital.¹

Upon admission, the patient was found to have profound leukopenia and neutropenia. Her white blood cell count was 1.0×103/uL, and her neutrophil count was 0.02×103/uL, indicating a serious adverse reaction to her medication regimen. Despite extensive testing ruling out infection, the patient received a diagnosis of neutropenic sepsis.¹

Treatment involved discontinuation of chlorpromazine and clozapine, aggressive intravenous antibiotic therapy, and administration of filgrastim 800 mcg to stimulate white blood cell production. The patient’s condition gradually improved, and she was discharged with a normal white blood cell count.¹

According to the investigators, this case highlights the complexities and risks associated with psychiatric polypharmacy. Although combination therapies may be necessary for patients with complex psychiatric conditions, they also increase the likelihood of adverse drug reactions.¹ In this case, the patient’s agranulocytosis—a rare but serious condition characterized by a dangerously low white blood cell count that affects 6 to 8 cases per million population yearly²—was attributed to the cumulative effects of multiple medications, including chlorpromazine and clozapine, which are known to carry a 0.13% and a 0.9% risk of agranulocytosis, respectively.¹

“This patient’s agranulocytosis was discovered in a timely manner, and the appropriate step of discontinuing the offending medications while ruling out sources of infection was made before more serious clinical problems arose,” the investigators wrote. “Drug-related blood dyscrasias leading to agranulocytosis carry with them a 5% to 10% mortality rate in Western countries. For this reason, clinicians should proceed cautiously when prescribing these medications on their own and in combination, as neutrophil counts before and during the administration of these drugs can monitor dropping neutrophil counts before a patient’s neutrophil number reaches 0.”

The investigators noted that this study’s results underscore the importance of careful medication management and monitoring in patients on polypharmacy regimens. Clinicians must remain vigilant for potential adverse reactions, particularly with medications known to pose risks of adverse effects such as agranulocytosis. Regular monitoring of white blood cell counts before and during treatment can help identify and mitigate adverse effects before they escalate.¹

“Clinicians must remain watchful of the potential consequences of drug interactions, particularly with medications such as chlorpromazine and clozapine known to predispose patients to agranulocytosis,” the investigators concluded. “Heightened awareness, regular monitoring, and individualized treatment plans are crucial in ensuring the safety and well-being of patients with complex psychiatric conditions on polypharmacy regimens.”

References

1. Villa NAE, Pausescu DG, Espiridion ED. Agranulocytosis associated with psychiatric polypharmacy: lessons learned from a clinical case. Cureus. 2024;16(3):e56701.

2. Sedhai YR, Lamichhane A, Gupta V. Agranulocytosis. In: StatPearls [Internet]. StatPearls Publishing; 2023. Updated May 23, 2023. Accessed May 13, 2024. https://www.ncbi.nlm.nih.gov/books/NBK559275/#:~:text=Agranulocytosis%20is%20a%20rare%20condition,per%20million%20population%20per%20year