Psychotic disorder induced by a combination of sorafenib and BAY86-9766

Abstract The Ras-Raf-mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK cascade is important in the intra-cellular transduction of neurotransmitters, such as dopamine and glutamate. Sorafenib (Nexavar), a multi-kinase inhibitor targeting Raf kinase, vascula...

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Published in:General hospital psychiatry 2014-07, Vol.36 (4), p.450.e5-450.e7
Main Authors: Kuo, Yen Lin, M.D, Yang, Yen Kuang, M.D, Cheng, Hsiu-Chi, M.D., Ph.D, Yen, Chia Jui, M.D., Ph.D, Chen, Po See, M.D., Ph.D
Format: Article
Language:English
Subjects:
Aged
BAY86-9766
Diphenylamine - administration & dosage
Diphenylamine - adverse effects
Diphenylamine - analogs & derivatives
Drug Therapy, Combination - adverse effects
ERK
Fatal Outcome
Humans
Liver Neoplasms - drug therapy
Lung Neoplasms - pathology
Male
MEK
Niacinamide - administration & dosage
Niacinamide - adverse effects
Niacinamide - analogs & derivatives
Phenylurea Compounds - administration & dosage
Phenylurea Compounds - adverse effects
Protein Kinase Inhibitors - administration & dosage
Protein Kinase Inhibitors - adverse effects
Psychiatry
Psychoses, Substance-Induced
Psychotic disorder
Sorafenib
Sulfonamides - administration & dosage
Sulfonamides - adverse effects
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Summary:Abstract The Ras-Raf-mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK cascade is important in the intra-cellular transduction of neurotransmitters, such as dopamine and glutamate. Sorafenib (Nexavar), a multi-kinase inhibitor targeting Raf kinase, vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor, has shown promising results in the treatment of malignancies. BAY86-9766, a novel selective MEK 1/2 inhibitor, is being evaluated in clinical trials as an anticancer drug. We describe herein a hepatocellular carcinoma patient presenting with recurrent psychotic symptoms in the course of the BASIL trial (assessing BAY86-9766 plus sorafenib for the treatment of liver cancer). In this case, VEGFR inhibition caused by sorafenib alone may have contributed to the development of psychosis. A change in ERK activity might also have been involved. However, whether single or combination use of the two drugs is responsible for inducing the psychotic symptoms remains unclear. In summary, the role of the ERK pathway in psychosis is still vague. Further investigation of the ERK activity in patients with psychotic disorders may disclose its role in the pathophysiology of psychosis.
ISSN:0163-8343
1873-7714
DOI:10.1016/j.genhosppsych.2012.03.001