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Factors associated with depressive state in patients with myasthenia gravis: a multicentre cross-sectional study.

ABSTRACT: Objectives The objective of this study was to examine clinical factors associated with depressive state in patients with myasthenia gravis (MG). Design Cross-sectional study. Setting and participants We evaluated 287 consecutive cases of MG seen at six neurological centres located in Eastern Japan. Outcome measures All MG patients completed the Japanese version of the Beck Depression Inventory-Second Edition (BDI-II). Disease severity was determined according to the MG Foundation of America (MGFA) quantitative MG score, MG activities of daily living scale and MG composite scale (MG composite). Clinical state following treatment was categorised according to MGFA postintervention status. Associations between detailed clinical parameters of MG and BDI-II score were then examined statistically. Results Mean BDI-II score for patients with MG (11.0±8.1) did not differ substantially from and overlapped with that reported as the Japanese standard (8.7±6.4). The mean +2 SDs for the Japanese standard is 21.5, approximately equal to the cut-off level indicative of moderate or worse depression (>20 points) in the original English version. We thus defined BDI-II >21.5 as depressive state, with a frequency of 13.6% in patients with MG. Multivariate logistic regression analysis revealed current dose of oral prednisolone (OR 1.09, 95% CI 1.02 to 1.17; p=0.01), unchanged MGFA postintervention status (OR 3.55, 95% CI 1.18 to 10.71; p=0.02), time since onset (OR 0.93, 95% CI 0.87 to 0.99; p=0.03) and MG composite (OR 1.16, 95% CI 1.00 to 1.34; p=0.046) as factors independently associated with depressive state in MG. Conclusions Dose of oral corticosteroids appears to represent the major factor associated with depressive state in MG. Unchanged status despite treatment and early disease stage are also significant background factors for depressive state, along with disease severity.

SUBMITTER: Suzuki Y

PROVIDER: S-EPMC3244661 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Factors associated with depressive state in patients with myasthenia gravis: a multicentre cross-sectional study.

Suzuki Yasushi Y Utsugisawa Kimiaki K Suzuki Shigeaki S Nagane Yuriko Y Masuda Masayuki M Kabasawa Chiaki C Shimizu Yuko Y Utsumi Hiroya H Uchiyama Shinichiro S Fujihara Kazuo K Suzuki Norihiro N

BMJ open 20111219 2

Objectives The objective of this study was to examine clinical factors associated with depressive state in patients with myasthenia gravis (MG). Design Cross-sectional study. Setting and participants We evaluated 287 consecutive cases of MG seen at six neurological centres located in Eastern Japan. Outcome measures All MG patients completed the Japanese version of the Beck Depression Inventory-Second Edition (BDI-II). Disease severity was determined according to the MG Foundation of America ( ...[more]

PMID: 22184587

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Project description:Myasthenia gravis (MG) is an autoimmune disease affecting the neuromuscular junction, whose clinical hallmark is muscle weakness and early fatigability. Azathioprine (AZA) is commonly used in Myasthenia Gravis therapy. AZA is a purine antagonist, which inhibits the cell cycle in the resting and DNA synthesis phases. It is usually used as an immunosuppressant to block T- and B-cell proliferation. AZA, bioconverted to 6-mercaptopurine by glutathione S-transferase (GST), can be metabolized either through the hypoxanthine phosphoribosyl transferase pathway to active 6-thioguanine nucleotides (6-TGN) or through the thiopurine S-methyltransferase (TPMT) pathway to inactive methyl-thiopurine metabolites. The incorporation of active 6-TGNs into DNA, causing breaks in DNA strands resulting in interference with RNA production and thereby protein synthesis, is responsible for the drug effect. The response to AZA is determined by which metabolic pathway is being favored. While balanced use of both HPRT and TPMT pathways results in responsiveness to AZA, hyperactivity of TPMT skews the balance towards the TPMT pathway and results in unresponsiveness to AZA with no pharmacological effect. In contrast, low TPMT activity skews the balance towards the HPRT pathway, resulting in increasing side-effects due to the accumulation of 6-TGNs. Current treatments for MG therapy are often inadequate because less than 40% of patients achieve complete remission with available drugs. This reflects the lack of drugs acting on target sites for which there is strong evidence of pathogenicity and the inability to identify responder patients. No criteria for responsiveness are available, exposing patients to unpredictable failures and unpredictable side effects. These individuals are at particular risk for adverse drug reaction (ADRs) or therapeutic failure. Genetic profiling with the Affymetrix drug metabolizing enzymes and transports genotyping array offers the ability to determine 1,931 variants and 225 genes involved in drug metabolism and disposition. Accordingly, the study of well-known drug-metabolizing genes can be involved in the specific metabolic pathway of a drug, which is more likely to define genotype-phenotype association and thereby genotype profiles relevant to drug response that can be applied as predictive biomarkers for pharmacological treatment.

Dataset Information

Factors associated with depressive state in patients with myasthenia gravis: a multicentre cross-sectional study.

Publications

Factors associated with depressive state in patients with myasthenia gravis: a multicentre cross-sectional study.

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