Hyperhomocysteinaemia in children receiving phenytoin and carbamazepine monotherapy: a cross-sectional observational study

Chandrasekaran, Saravanan; Patil, Sooraj; Suthar, Renu; Attri, Savita Verma; Sahu, Jitendra Kumar; Sankhyan, Naveen; Tageja, Mini; Singhi, Pratibha

doi:10.1136/archdischild-2016-311436

Cited by 9 publications

(12 citation statements)

References 28 publications

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“…[15,19,20] Three studies were performed in India. [21,22,23] One study was conducted in each of Turkey, [16] USA, [12] Korea, [24] and Germany. [11] Among included studies, 6 papers [15,16,19–21,22] reported the serum levels of all 3 parameters.…”

Section: Resultsmentioning

confidence: 99%

“…[21,22,23] One study was conducted in each of Turkey, [16] USA, [12] Korea, [24] and Germany. [11] Among included studies, 6 papers [15,16,19–21,22] reported the serum levels of all 3 parameters. One of them had levels of folate and vitamin B12 [11] and the 2 studies had the level of Hcy, [12,23] and the last one had solely level of Hcy and folate.…”

Section: Resultsmentioning

confidence: 99%

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Effects of phenytoin on serum levels of homocysteine, vitamin B12, folate in patients with epilepsy

Zhang

et al. 2019

Medicine

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Background: To determine the influence of phenytoin (PHT) monotherapy on the serum levels of homocysteine (Hcy), folate and vitamin B12 in patients with epilepsy. Methods: Literature retrieval was performed through PubMed, Web of Science, Embase, Cochrane Library, Chinese Wanfang Data, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database databases as of the end of March 2018. Pooled weighted mean difference (WMD) and 95% CIs were calculated using a random effect model. Results: A total of ten eligible studies were identified. The result revealed that the serum level of homocysteine in PHT-treated patients with epilepsy was significantly higher than that in control group (WMD = 8.47, 95% CI: 6.74 to 10.20, P < .001). In addition, the serum levels of folate (WMD = −3.51, 95% CI: −4.20 to −2.83, P < .001) and vitamin B12 (WMD = −62.23, 95% CI: −83.27 to −41.19, P < .001) were decreased significantly compared with the control group. Conclusions: Our meta-analysis indicates that PHT monotherapy is associated with the increase in the serum homocysteine levels and decreased levels of folate and vitamin B12, and hyperhomocysteinaemia may contribute to the acceleration of the atherosclerotic process. Therefore, the patients under these medications should be monitored plasma homocysteine.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Effects of phenytoin on serum levels of homocysteine, vitamin B12, folate in patients with epilepsy

Zhang

et al. 2019

Medicine

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“…However, a decrease in MTHFR activity by phenytoin treatment at therapeutic plasma levels was observed in mice [21]. Enzyme-promoting AEDs such as phenytoin and phenobarbital are known to cause riboflavin and folate deficiencies via induction of cytochrome P450 [16, 22]. It has been reported that phenytoin decreases serum pyridoxal levels, leading to hyperhomocysteinemia [23].…”

Section: Discussionmentioning

confidence: 99%

Antiepileptic drug-induced psychosis associated with MTHFR C677T: a case report

et al. 2019

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Background Various antiepileptic drugs can potentially cause psychiatric side effects in patients with epilepsy, but the precise mechanism of these actions remains unknown. In recent years, the common polymorphism C677T in the 5,10-methylenetetrahydrofolate reductase ( MTHFR ) gene has attracted attention for its role in the onset of psychiatric diseases. MTHFR and several vitamins (as cofactors) are crucial for remethylation of homocysteine via folate and homocysteine metabolism. We report a case of a Japanese patient who presented with reversible schizophrenia-like symptoms during antiepileptic drug therapy. Case presentation Our patient had frontal lobe epilepsy and had been treated with several antiepileptic drugs since the age of 13 years. He developed auditory hallucinations and multiple personalities at 17 years of age, several months after the initiation of phenytoin and phenobarbital, despite these antiepileptic drugs being used within the therapeutic ranges. Genetic analysis revealed that he was homozygous for the C677T polymorphism of MTHFR . Hyperhomocysteinemia, hypomethionemia, and multiple vitamin deficiencies, including folate, riboflavin, and pyridoxal, were identified at the age of 23 years. Vitamin supplementation and alteration of the antiepileptic drugs improved his psychotic symptoms. Multiple vitamin deficiencies with homozygous MTHFR C677T should be considered in patients presenting with schizophrenia-like symptoms during antiepileptic drug therapy. Conclusions To the best of our knowledge, this is the first report of antiepileptic drug-induced psychosis associated with homozygous C677T and multiple vitamin deficiencies. Our findings will contribute to the elucidation of the pathogenesis of the psychiatric side effects of antiepileptic drugs and lead to improved medical management for patients with epilepsy.

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“…After one year of sup plementation, the authors observed a significant de cline in the Beck Depression Inventory, in the hyper homocysteinemia, and in seizure frequency observed (Bochyńska et al 2012). In another study of children receiving carbamazepine and phenytoin treatment, supplementation with 5 mg/day folic acid for one month was associated with an increase in serum homocysteine levels, and a reduction in B 12 and folic acid levels (Chandrasekaran et al 2017). Supplementation was also associated with a reduction in plasma homocysteine concentrations in the study group (Chandrasekaran et al 2017).…”

Section: Introductionmentioning

confidence: 93%

“…In another study of children receiving carbamazepine and phenytoin treatment, supplementation with 5 mg/day folic acid for one month was associated with an increase in serum homocysteine levels, and a reduction in B 12 and folic acid levels (Chandrasekaran et al 2017). Supplementation was also associated with a reduction in plasma homocysteine concentrations in the study group (Chandrasekaran et al 2017). Given these results levels of vitamin B 6, vitamin B 12 , and folic acid should be monitored among patients receiving anticonvulsant drugs, and supplementation may be beneficial (Bochyńska et al 2012, Chandrasekaran et al 2017).…”

Section: Introductionmentioning

confidence: 95%

Role of food-drug interactions in neurological and psychological diseases

Karadağ¹,

Çelik²,

Kadayifçi³

et al. 2018

Acta Neurobiologiae Experimentalis

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Given that foods and nutrients have been shown to influence the pharmacokinetics of drugs, drugs may cause changes in the nutritional status of patients and their response to a given drug. Food-drug interactions are particularly relevant for drugs used to treat neurological and psychological diseases. This review provides an overview of food-drug interaction in the treatment of neurological and psychological diseases. A literature search was carried out by collecting data from different reviews, reports, and original articles on general or specific drug interactions with food, in patients with a variety of neurological and psychological diseases. Based on our review, we found that food-drug interactions may alter the expected impact of drug, or cause the development of a drug toxicity. Nutritional status of the patients may also be affected, particularly a change in body weight caused by a change appetite. Metabolism, absorption, and excretion of foods may also be altered, and nutritional insufficiencies may occur. Recent studies show that diet can have a strong influence on gut microbiota and thus, alter drug pharmacokinetics.Therefore, microbiota alterations should also be considered while assessing food-drug interactions. Knowledge of food-drug interactions is critical for improving health of patients with neurological and psychological diseases, and also for improving effectiveness of treatments.

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Hyperhomocysteinaemia in children receiving phenytoin and carbamazepine monotherapy: a cross-sectional observational study

Abstract: Phenytoin or carbamazepine monotherapy for >6 months duration is associated with hyperhomocysteinaemia in 90% of North Indian children. Elevated homocysteine concentrations were normalised in these children with folic acid supplementation.

Cited by 9 publications

References 28 publications

Effects of phenytoin on serum levels of homocysteine, vitamin B12, folate in patients with epilepsy

Effects of phenytoin on serum levels of homocysteine, vitamin B12, folate in patients with epilepsy

Antiepileptic drug-induced psychosis associated with MTHFR C677T: a case report

Role of food-drug interactions in neurological and psychological diseases

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