Association Between Voriconazole-induced Visual Hallucination and Dopamine in an Analysis of the Food and Drug Administration (FDA) Adverse Event Reporting System Database

Overview

Journal Sci Rep

Specialty Science

Date 2024 May 31

PMID 38822123

Authors

Hideo Kato

Chihiro Shiraishi

Mao Hagihara

Hiroshige Mikamo

Takuya Iwamoto

Affiliations

Soon will be listed here.

Abstract

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.

References

Zhong M, Gu R, Zhu S, Bai Y, Wu Z, Jiang X . Prevalence and Risk Factors for Minor Hallucinations in Patients with Parkinson's Disease. Behav Neurol. 2021; 2021:3469706. PMC: 8505047. DOI: 10.1155/2021/3469706. View

Anzai T, Takahashi K, Watanabe M, Mochizuki M, Murashima A . Adverse event reports in patients taking psychiatric medication during pregnancy from spontaneous reports in Japan and the United States: an approach using latent class analysis. BMC Psychiatry. 2020; 20(1):118. PMC: 7068895. DOI: 10.1186/s12888-020-02525-z. View

Capogrosso Sansone A, Convertino I, Galiulo M, Salvadori S, Pieroni S, Knezevic T . Muscular Adverse Drug Reactions Associated with Proton Pump Inhibitors: A Disproportionality Analysis Using the Italian National Network of Pharmacovigilance Database. Drug Saf. 2017; 40(10):895-909. DOI: 10.1007/s40264-017-0564-8. View

Raschi E, Poluzzi E, Salvo F, Pariente A, De Ponti F, Marchesini G . Pharmacovigilance of sodium-glucose co-transporter-2 inhibitors: What a clinician should know on disproportionality analysis of spontaneous reporting systems. Nutr Metab Cardiovasc Dis. 2018; 28(6):533-542. DOI: 10.1016/j.numecd.2018.02.014. View

Brown E, Wood L, Wood S . The medical dictionary for regulatory activities (MedDRA). Drug Saf. 1999; 20(2):109-17. DOI: 10.2165/00002018-199920020-00002. View

Kullberg B, Sobel J, Ruhnke M, Pappas P, Viscoli C, Rex J . Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial. Lancet. 2005; 366(9495):1435-42. DOI: 10.1016/S0140-6736(05)67490-9. View

Sakaeda T, Tamon A, Kadoyama K, Okuno Y . Data mining of the public version of the FDA Adverse Event Reporting System. Int J Med Sci. 2013; 10(7):796-803. PMC: 3689877. DOI: 10.7150/ijms.6048. View

Kapur S . How antipsychotics become anti-"psychotic"--from dopamine to salience to psychosis. Trends Pharmacol Sci. 2004; 25(8):402-6. DOI: 10.1016/j.tips.2004.06.005. View

Bate A, Evans S . Quantitative signal detection using spontaneous ADR reporting. Pharmacoepidemiol Drug Saf. 2009; 18(6):427-36. DOI: 10.1002/pds.1742. View

10.

Cojutti P, Merelli M, Allegri L, Damante G, Bassetti M, Pea F . Successful and safe long-term treatment of cerebral aspergillosis with high-dose voriconazole guided by therapeutic drug monitoring. Br J Clin Pharmacol. 2018; 85(1):266-269. PMC: 6303198. DOI: 10.1111/bcp.13789. View

11.

Zhai S, Tanimura A, Graves S, Shen W, Surmeier D . Striatal synapses, circuits, and Parkinson's disease. Curr Opin Neurobiol. 2017; 48:9-16. PMC: 6022405. DOI: 10.1016/j.conb.2017.08.004. View

12.

Strandell J, Caster O, Bate A, Noren N, Ralph Edwards I . Reporting patterns indicative of adverse drug interactions: a systematic evaluation in VigiBase. Drug Saf. 2011; 34(3):253-66. DOI: 10.2165/11586990-000000000-00000. View

13.

Donnelly J, De Pauw B . Voriconazole-a new therapeutic agent with an extended spectrum of antifungal activity. Clin Microbiol Infect. 2004; 10 Suppl 1:107-17. DOI: 10.1111/j.1470-9465.2004.00838.x. View

14.

Rajendran R, Menon K, Nair S . Nanotechnology Approaches for Enhanced CNS Drug Delivery in the Management of Schizophrenia. Adv Pharm Bull. 2022; 12(3):490-508. PMC: 9348538. DOI: 10.34172/apb.2022.052. View

15.

Sakurada H, Yasuhara K, Kato K, Asano S, Yoshida M, Yamamura M . An investigation of visual hallucinations associated with voriconazole administration to patients with hematological malignancies. Pharmazie. 2018; 71(11):660-664. DOI: 10.1691/ph.2016.6725. View

16.

Walsh T, Anaissie E, Denning D, Herbrecht R, Kontoyiannis D, Marr K . Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008; 46(3):327-60. DOI: 10.1086/525258. View

17.

Kato H, Hagihara M, Hamada Y, Koizumi Y, Nishiyama N, Yamagishi Y . Visual disturbance or central symptom like hallucination in patients treated voriconazole: report of six cases. Jpn J Antibiot. 2018; 69(3):143-150. View