Association between voriconazole-induced visual hallucination and dopamine in an analysis of the food and drug administration (FDA) adverse event reporting system database

• Published in: Scientific reports Vol. 14; no. 1; pp. 12519 - 5
• Main Authors: Kato, Hideo, Shiraishi, Chihiro, Hagihara, Mao, Mikamo, Hiroshige, Iwamoto, Takuya
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 31-05-2024; Nature Publishing Group; Nature Portfolio
• Subjects: 692/1807/1693; 692/420/254; 692/499; Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Adverse events; Aged; Antagonists; Antifungal Agents - adverse effects; Chlorpromazine; Chlorpromazine - adverse effects; Databases, Factual; Dopamine; Dopamine - metabolism; Dopamine Antagonists - adverse effects; Dopamine receptors; Female; Hallucinations; Hallucinations - chemically induced; Humanities and Social Sciences; Humans; Levodopa; Levodopa - adverse effects; Male; Mental disorders; Middle Aged; multidisciplinary; Neurodegenerative diseases; Parkinson Disease - drug therapy; Parkinson's disease; Risperidone; Risperidone - adverse effects; Schizophrenia; Science; Science (multidisciplinary); United States - epidemiology; United States Food and Drug Administration; Visual hallucination; Voriconazole; Voriconazole - adverse effects; Young Adult; United States; Visual hallucination; Dopamine; Voriconazole
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-63504-y

Voriconazole is a second-generation azole used to treat serious fungal infections. Visual hallucinations constitute a representative adverse event caused by voriconazole. However, its mechanism of action remains unclear. In patients with schizophrenia or Parkinson’s disease, the frequency of visual hallucinations is associated with brain dopamine levels. This study investigated the frequency of visual hallucinations in patients treated with voriconazole alone or in combination with dopaminergic medicines or dopamine antagonists, using data collected from the Food and Drug Administration Adverse event Reporting System (FAERS). The frequency of visual hallucinations with voriconazole alone and in combination with a dopaminergic medicine (levodopa) or dopamine antagonists (risperidone and chlorpromazine) was compared using data from the FAERS between 2004 and 2023, using the reporting odds ratio (ROR) with relevant 95% confidence intervals (CI). The reference group comprised patients who had been administered voriconazole without dopaminergic medication or dopamine antagonists. Of the patients, 22,839, 90,810, 109,757, 6,435, 20, 83, and 26, respectively were treated with voriconazole, levodopa, risperidone, chlorpromazine, voriconazole plus levodopa, voriconazole plus risperidone, and voriconazole plus chlorpromazine. The occurrence of visual hallucinations increased when used in combination with levodopa (ROR = 12.302, 95% CI = 3.587–42.183). No increase in incidence was associated with the concomitant use of dopamine antagonists (risperidone, ROR = 1.721, 95% CI = 0.421–7.030; chlorpromazine, ROR = none, 95% CI = none). Dopaminergic medicine may increase the risk of visual hallucinations in patients treated with voriconazole. Whether voriconazole positively modulates dopamine production warrants further investigation using a translational research approach.