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Fulltext Clinical use of mood stabilizers beyond treatment for bipolar disorder: The REAP-MS study

Chen CK, Yang SY, Park SC, Jang OJ, Zhu X, Xiang YT, et al.

Asian J Psychiatr, 2023 Jul;85:103613.
PMID: 37163943 DOI: 10.1016/j.ajp.2023.103613

OBJECTIVE: Mood stabilizers are psychotropic drugs mainly used to treat bipolar disorder in the acute phase or for maintenance therapy to prevent relapse. In clinical practice, mood stabilizers are commonly prescribed for conditions other than bipolar disorder. This study investigated the distribution of mood stabilizer prescriptions for different psychiatric diagnoses and studied differences in the drugs, dosage, and plasma concentration in 10 Asian countries including Taiwan, South Korea, Malaysia, China, Thailand, India, Pakistan, Singapore, Indonesia, and Myanmar.
METHODS: Patients prescribed mood stabilizers (lithium, carbamazepine, valproic acid, or lamotrigine) for a psychiatric condition other than bipolar disorder (codes F31.0-F31.9 in the International Classification of Diseases, 10th Edition, Clinical Modification) were recruited through convenience sampling. A website-based data entry system was used for data collection.
RESULTS: In total, 1557 psychiatric patients were enrolled. Schizophrenia, schizotypal, delusional, and other non-mood psychotic disorders (F20-F29, 55.8 %) was the most common diagnosis, followed by non-bipolar mood disorders (F30, F31- F39, 25.3 %), organic mental disorder (F00-F09, 8.8 %), mental retardation (F70-F79, 5.8 %) and anxiety, dissociative, stress-related, somatoform and other nonpsychotic mental disorders (F40-F48, 4.4 %). The most frequently targeted symptoms (>20 %) were irritability (48 %), impulsivity (32.4 %), aggression (29.2 %), anger (20.8 %), and psychosis (24.1 %). Valproic acid was the most frequently used medication.
CONCLUSIONS: Clinicians typically prescribe mood stabilizers as empirically supported treatment to manage mood symptoms in patients with diagnoses other than bipolar disorders, though there is on official indication for these disorders. The costs and benefits of this add-on symptomatic treatment warrant further investigation.

Matched MeSH terms: Valproic Acid/therapeutic use
Sodium valproate-aggravated psoriasiform eruption

Kwan Z, Che Ismail RB, Wong SM, Tan LL, Robinson S, Lim KS

Int J Dermatol, 2014 Oct;53(10):e477-9.
PMID: 25209632 DOI: 10.1111/ijd.12579
Matched MeSH terms: Valproic Acid/adverse effects*
Toxicity and teratogenicity effects of valproic acid on zebrafish (Danio rerio) embryos in relation to autism spectrum disorder

Saleh Hodin NA, Chong SG, Bakar NA, Fahmi MSAM, Ramlan NF, Hamid NNAZZ, et al.

Birth Defects Res, 2023 Oct 01;115(16):1475-1485.
PMID: 37507847 DOI: 10.1002/bdr2.2227

Valproic acid (VPA) is a widely prescribed antiepileptic drug with various medicinal efficacies. Accumulated evidence implied that prenatal exposure to VPA is highly associated with autism spectrum disorder (ASD). In this study, the zebrafish were exposed to a set of VPA concentrations (0, 5, 10, 20, 40, 80, 160, 320, 640, 1280, and 2560 μM) at 5 h post fertilization (hpf) to 120 hpf. The adverse effects of VPA were extensively studied through the evaluations on the mortality, heartbeats, spontaneous tail coiling, and hatching rate. Morphological observations were conducted at 120 hpf, following the exposure termination. Basic locomotor responses and anxiety-like behavioral alterations evaluated for behavioral impairments are the hallmark feature of ASD. The exposure to VPA at teratogenic concentrations reduced the aforementioned parameters in a dose-dependent manner (p ≤ .05). At the selected non-teratogenic concentrations of VPA, the treated larvae demonstrated profound alterations of basic locomotor responses. No significant changes of anxiety and thigmotactic behaviors were observed on the VPA-treated fish compared to the control (p ≥ .005). This study depicted that embryonic zebrafish exposure to VPA produced significant toxicity and teratogenicity effects as well as the alterations of basic behavioral responses. Overall, this study provides a fundamental insight of the toxicity effects at morphological and behavioral levels to facilitate the understanding of ASD mechanisms at different molecular levels.

Matched MeSH terms: Valproic Acid/toxicity
Valproate-induced reversible sensorineural hearing loss: a case report with serial audiometry and pharmacokinetic modelling during a valproate rechallenge

Yeap LL, Lim KS, Lo YL, Bakar MZ, Tan CT

Epileptic Disord, 2014 Sep;16(3):375-9.
PMID: 25167568 DOI: 10.1684/epd.2014.0671

Hearing loss has been reported with valproic acid (VPA) use. However, this is the first case of VPA-induced hearing loss that was tested and confirmed with a VPA rechallenge, supported by serial audiometry and pharmacokinetic modelling. A 39-year-old truck driver with temporal lobe epilepsy was treated with VPA at 400 mg, twice daily, and developed hearing loss after each dose, but recovered within three hours. Hearing loss fully resolved after VPA discontinuation. Audiometry performed five hours after VPA rechallenge showed significant improvement in hearing thresholds. Pharmacokinetic modelling during the VPA rechallenge showed that hearing loss occurred at a level below the therapeutic range. Brainstem auditory evoked potential at three months after VPA discontinuation showed bilateral conduction defect between the cochlear and superior olivary nucleus, supporting a pre-existing auditory deficit. VPA may cause temporary hearing threshold shift. Pre-existing auditory defect may be a risk factor for VPA-induced hearing loss. Caution should be taken while prescribing VPA to patients with pre-existing auditory deficit.

Matched MeSH terms: Valproic Acid/adverse effects*; Valproic Acid/pharmacokinetics; Valproic Acid/therapeutic use
Fulltext Synthesis, Characterization, and Anti-Cancer Activity of Some New N'-(2-Oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazones Derivatives

El-Faham A, Farooq M, Khattab SN, Abutaha N, Wadaan MA, Ghabbour HA, et al.

Molecules, 2015;20(8):14638-55.
PMID: 26287132 DOI: 10.3390/molecules200814638

Eight novel N'-(2-oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazone derivatives 4a-h were synthesized and fully characterized by IR, NMR ((1)H-NMR and (13)C-NMR), elemental analysis, and X-ray crystallography. The cyto-toxicity and in vitro anti-cancer evaluation of the prepared compounds have been assessed against two different human tumour cell lines including human liver (HepG2) and leukaemia (Jurkat), as well as in normal cell lines derived from human embryonic kidney (HEK293) using MTT assay. The compounds 3e, 3f, 4a, 4c, and 4e revealed promising anti-cancer activities in tested human tumour cells lines (IC50 values between 3 and 7 μM) as compared to the known anti-cancer drug 5-Fluorouracil (IC50 32-50 μM). Among the tested compounds, 4a showed specificity against leukaemia (Jurkat) cells, with an IC50 value of 3.14 μM, but this compound was inactive in liver cancer and normal cell lines.

Matched MeSH terms: Valproic Acid/analogs & derivatives*; Valproic Acid/chemical synthesis; Valproic Acid/pharmacology
Fulltext Treatment-emergent hypomania or bipolar disorder? A case report

Yin, Ping Ng, Saminah Md Kassim, Maniam, T.

ASEAN Journal of Psychiatry, 2013;14(2):157-160.
MyJurnal

Objective: This case report highlights the clinical dilemmas encountered in deciding the diagnostic status of persons with unipolar depression who develop hypomania during antidepressant/electroconvulsive therapy.

Methods: We report a case of a 52 year-old Chinese lady, diagnosed with unipolar depression, which developed hypomania after she was started on T. Fluvoxamine 100mg daily and completed 8 sessions of Electroconvulsive therapy.

Results: Her diagnosis was revised to Bipolar Disorder and she was treated with T. Sodium Valproate 400mg twice daily after which she improved.

Conclusion: Treatment-emergent hypomania is likely a subtype of bipolar spectrum disorder and patients with Treatment - emergent Hypomania should be treated as Bipolar Disorder.

Matched MeSH terms: Valproic Acid
Fulltext Improvement of "Bouncy Gait" in Lance-Adams Syndrome with Perampanel

Lim SY, Jasti DB, Tan AH

Cureus, 2020 Jan 25;12(1):e6773.
PMID: 32117660 DOI: 10.7759/cureus.6773

Lance-Adams syndrome (LAS) is chronic post-hypoxic myoclonus that is often associated with sudden lapses in muscle tone (negative myoclonus) in the legs, causing a disabling "bouncy gait." Given its relative rarity, there are no controlled treatment studies of LAS. The majority of cases require polypharmacy management, with an incomplete response. "Bouncy gait," in particular, is notoriously medication-refractory. Here, we report a patient with long-standing LAS who improved markedly when low-dose perampanel was added to his existing treatment regime consisting of clonazepam, levetiracetam, sodium valproate, and acetazolamide.

Matched MeSH terms: Valproic Acid
Association between ABCB1 polymorphism and response to sodium valproate treatment in Malaysian epilepsy patients

Haerian BS, Lim KS, Tan HJ, Mohamed EH, Tan CT, Raymond AA, et al.

Epileptic Disord, 2011 Mar;13(1):65-75.
PMID: 21388909 DOI: 10.1684/epd.2011.0419

Over-expression of P-glycoprotein, encoded by the ABCB1 gene, is proposed to be involved in resistance to antiepileptic drugs in about 30% of patients with epilepsy. Here, we investigated the possible association between ABCB1 polymorphisms and sodium valproate (VPA) treatment in Malaysian epilepsy patients. Genotypes were assessed in 249 drug-resistant and 256 drug-responsive Malaysian patients for C1236T, G2677T/A, and C 5T polymorphisms in the ABCB1 gene. No genotypes, alleles, or haplotypes were associated with the response to VPA in either the overall group or Chinese, Indian, and Malay subgroups. Our data suggest that C1236T, G2677T/A, and C3435T polymorphisms in the ABCB1 gene do not contribute to the response to VPA in patients with epilepsy.

Matched MeSH terms: Valproic Acid/therapeutic use*
The use of lamotrigine and other antiepileptic drugs in paediatric patients at a Malaysian hospital

Ab Rahman AF, Ibrahim MI, Ismail HI, Seng TB

Pharm World Sci, 2005 Oct;27(5):403-6.
PMID: 16341748

OBJECTIVE: (1) To determine the effect of lamotrigine add-on therapy on the seizure frequency and cost in paediatric patients. (2) To determine the prescribing pattern of other antiepileptic drugs (AEDs).

METHOD: A retrospective study of medical records was carried out from October 2000 to June 2001 at the paediatric clinic, Hospital Pulau Pinang.

MAIN OUTCOME MEASURE: Seizure frequency, cost of drug and types of AED prescribed.

RESULTS: A total of 209 medical records were retrieved during the study period. Lamotrigine (LTG) was prescribed in 29 patients as add-on therapy. In 18 patients, there was a significant reduction in seizure frequency after the addition of LTG. Approximately 70% experienced a reduction in seizure frequency of more than 50%. Side effects of LTG were considered mild and manageable. However, drug cost after the addition of LTG increased by 103%. In the remaining 180 patients, the most common AED prescribed was sodium valproate (VPA). Only 15% of the patients received combination therapy. Mean monthly cost of monotherapy was found to be RM 24.4 while monthly cost of combination therapy was RM 45.4 (1 Euro-RM 5.00).

CONCLUSION: The majority of paediatric patients in the study are on AED monotherapy and only a small percentage was prescribed lamotrigine. The use of lamotrigine is associated with better seizure control but with an increase in drug cost.

Study site: paediatric clinic, Hospital Pulau Pinang.

Matched MeSH terms: Valproic Acid/economics; Valproic Acid/therapeutic use
Fulltext Pharmacokinetic parameters of valproic acid and carbamazepine from routinely collected data: influence of patient characteristics

Hasnah Ibrahim, Fatah Ab Rahman

Malaysian Journal of Pharmaceutical Science, 2008;6(1):33-42.
MyJurnal

Individualising a drug dosage regimen is more appropriate if it is based on pharmacokinetics data derived from local populations. In this study, we estimated valproic acid (VPA) and carbamazepine (CBZ) clearances in the Malaysian population from routinely collected therapeutic drug monitoring (TDM) data. We also evaluated the effects of gender, age, weight and concurrent antiepileptic drug (AED) therapy on VPA and CBZ clearance. Data was collected retrospectively from TDM forms of adult patients. Apparent drug clearance was estimated based on the standard steady state clearance equation. Mann-Whitney and KruskalWallis tests were used to evaluate gender and therapy differences, while Spearman’s Rank correlation was used to determine the associations of age and weight with clearance. One hundred thirty-two samples for VPA and 67 for CBZ were included in the analysis. Patients’ ages ranged from 15 to 72 years old. Mean VPA and CBZ clearances were found to be 0.36 l/kg/d and 1.60 l/kg/d, respectively. VPA clearance correlated positively but poorly with weight. Our results showed significant differences in (i) VPA clearance among male and female patients and (ii) VPA clearance between monotherapy and combination therapy. These findings provide a guide to initiate maintenance doses of VPA and CBZ in our local patients. Awareness of factors influencing drug clearance should help to optimise patients’ dosing regimens.

Matched MeSH terms: Valproic Acid
Fulltext Evaluation of blood sampling times and indications for therapeutic drug monitoring services

Aishah Hamzah, Ab Fatah Ab Rahman

Malaysian Journal of Pharmaceutical Science, 2008;6(1):1-11.
MyJurnal

The appropriateness of sampling times and indications for monitoring of serum drug concentrations for the purpose of therapeutic drug monitoring (TDM) were evaluated at three hospitals on the east coast of Malaysia. Appropriateness criteria for indication and sampling were adapted from previously published criteria and with input from local TDM pharmacists. Six drugs were chosen, namely gentamicin, digoxin, carbamazepine, phenobarbital, phenytoin, and valproic acid. A total of 265 TDM requests were evaluated. Appropriateness of the indication for TDM ranged from 77.4% to 82%, while that for sampling ranged from 34.2% to 62.1%. There were no significant differences between the three hospitals in both categories of appropriateness. Among different drug groups, the percentage of appropriate indication was found to be highest with antiepileptic drugs. Antiepileptic drugs, however, had the lowest rate of appropriate sampling. Overall, findings from the three hospitals showed very encouraging results with almost 80% of the requests considered as appropriately indicated. However, the percentage of appropriateness of sampling was lower, and thus may require further investigation.

Matched MeSH terms: Valproic Acid
Characterisation, in-vitro and in-vivo evaluation of valproic acid-loaded nanoemulsion for improved brain bioavailability

Tan SF, Kirby BP, Stanslas J, Basri HB

J Pharm Pharmacol, 2017 Nov;69(11):1447-1457.
PMID: 28809443 DOI: 10.1111/jphp.12800

OBJECTIVE: This study was aimed to investigate the potential of formulated valproic acid-encapsulated nanoemulsion (VANE) to improve the brain bioavailability of valproic acid (VPA).
METHODS: Valproic acid-encapsulated nanoemulsions were formulated and physically characterised (osmolarity, viscosity, drug content, drug encapsulation efficiency). Further investigations were also conducted to estimate the drug release, cytotoxic profile, in-vitro blood-brain barrier (BBB) permeability, pharmacokinetic parameter and the concentration of VPA and VANE in blood and brain.
KEY FINDINGS: Physical characterisation confirmed that VANE was suitable for parenteral administration. Formulating VPA into nanoemulsion significantly reduced the cytotoxicity of VPA. In-vitro drug permeation suggested that VANEs crossed the BBB as freely as VPA. Pharmacokinetic parameters of VANE-treated rats in plasma and brain showed F3 VANE had a remarkable improvement in AUC, prolongation of half-life and reduction in clearance compared to VPA. Given the same extent of in-vitro BBB permeation of VPA and VANE, the higher bioavailability of VANE in brain was believed to have due to higher concentration of VANE in blood. The brain bioavailability of VPA was improved by prolonging the half-life of VPA by encapsulating it within the nanoemulsion-T80.
CONCLUSIONS: Nanoemulsion containing VPA has alleviated the cytotoxic effect of VPA and improved the plasma and brain bioavailability for parenteral delivery of VPA.

Matched MeSH terms: Valproic Acid
Fulltext Lack of association of ABCB1 haplotypes on five loci with response to treatment in epilepsy

Haerian BS, Lim KS, Mohamed EH, Tan HJ, Tan CT, Raymond AA, et al.

Seizure, 2011 Sep;20(7):546-53.
PMID: 21530324 DOI: 10.1016/j.seizure.2011.04.003

Approximately one third of newly treated epilepsy patients do not respond to antiepileptic drugs (AEDs). Overexpression of P-glycoprotein (P-gp) efflux transporter has been proposed to have a critical role in causing resistance to AEDs. P-gp is a product of the ATP-binding cassette subfamily B member 1 (ABCB1) gene. The purpose of this study was to investigate a possible link between ABCB1 rs3789243 C>T, C1236T, G2677T/A, rs6949448 C>T, and C3435T haplotypes with response to carbamazepine (CBZ) or sodium valproate (VPA) monotherapy in Malaysian epilepsy patients. No ABCB1 haplotype association was found with response to either CBZ or VPA monotherapy in the Chinese, Indian, and Malay patients. C3435 allele carriers of the Indian males with cryptogenic epilepsy were more prone to resistance to either CBZ or VPA than carriers of T allele. Moreover, rs3789243T allele carriers of Malay females with symptomatic epilepsy were more resistant to either CBZ or VPA than C allele carriers. Our findings suggest that the ABCB1 rs3789243 C>T, C1236T, G2677T/A, rs6949448 C>T, and C3435T haplotypes do not contribute to response to AED treatment in epilepsy.

Matched MeSH terms: Valproic Acid/therapeutic use
SCN1A IVS5N+5 polymorphism and response to sodium valproate: a multicenter study

Haerian BS, Baum L, Tan HJ, Kwan P, Raymond AA, Saruwatari J, et al.

Pharmacogenomics, 2012 Oct;13(13):1477-85.
PMID: 23057548 DOI: 10.2217/pgs.12.127

Approximately 30% of epilepsy patients do not response to antiepileptic drugs (AEDs). The functional SCN1A IVS5N+5 polymorphism may play a role in response to some AEDs. The purpose of this study was to examine this hypothesis in a cohort study of Malaysian and Hong Kong Chinese epilepsy patients on sodium valproate (VPA) monotherapy and in a meta-analysis.

Matched MeSH terms: Valproic Acid/pharmacology*
Fulltext Manic switch on mirtazapine: a case report

Khairani Yahya, Azizah Saie

Malaysian Journal of Psychiatry, 2018;27(1):0-0.
MyJurnal

In recent years, more cases of manic switches on Mirtazapine have been reported. In this report, we discuss a case of manic switch in a gentleman who was treated as unipolar depression. A 66-year-old man presented to psychiatry 8 months following a nephrectomy for symptoms of depression. Treatment with Sertraline 50mg daily was initiated and titrated to 150mg, along with Zolpidem and Clonazepam to aid his sleep. Despite these medications he never achieved remission and continued to have persistent anxiety and insomnia. Due to suboptimal control, treatment was changed to Mirtazapine 15mg daily. At day 20 he showed symptoms of mania which included talkativeness, increased goal directed activities, reduced need for sleep and socially disinhibited behavior. Mirtazapine was discontinued, and treatment was changed to Sodium Valproate, optimized to 1000mg daily, augmented with Quetiapine 150mg daily. Remission was achieved after 4 months and he has remained asymptomatic for 2 months. This was his first episode of mania, and a diagnosis of Bipolar I disorder was made. In conclusion, antidepressant induced manic switches are common, they are relatively under-appreciated and under-reported, especially with the use of sleep-promoting antidepressants. All antidepressants should be considered to be a potential mediator of a switch in view of its pharmacological properties.

Matched MeSH terms: Valproic Acid
Fulltext Sodium valproate induced necrotising pancreatitis: A case report

Ali MF, Loh KY

Malays Fam Physician, 2013;8(3):28-30.
PMID: 25893054 MyJurnal

Sodium valproate is one of the most common first-line antiepileptics prescribed for primary and secondary generalised seizures. However, serious complications associated with sodium valproate, such as acute pancreatitis, need to be considered when choosing this medication for treating epilepsy in certain populations such as children and persons with intellectual disability. We report a case of a 21-year-old man with intellectual disability who presented to the emergency department with an acute abdomen, vomiting and diarrhoea. He had to undergo an emergency exploratory laparotomy during which acute necrotising pancreatitis was diagnosed intra-operatively. We believe that the recent increase in sodium valproate dosage for his epilepsy was the cause of the pancreatitis. Carers of such persons should be adequately informed regarding possible life-threatening complications of medications prescribed to avoid delay in diagnosis and unwanted incidents.

Matched MeSH terms: Valproic Acid
Fulltext Age-Dependent Anti-migraine Effects of Valproic Acid and Topiramate in Rats

Huang P, Kuo PH, Lee MT, Chiou LC, Fan PC

Front Pharmacol, 2018;9:1095.
PMID: 30319425 DOI: 10.3389/fphar.2018.01095

Background: Valproic acid (VPA) and topiramate (TPM), initially developed as antiepileptics, are approved for migraine prophylaxis in adults but not children. The differences in their antimigraine mechanism(s) by age remain unclear. Methods: A migraine model induced by intra-cisternal (i.c.) capsaicin instillation in pediatric (4-5 weeks) and adult (8-9 weeks) rats was pretreated with VPA (30, 100 mg/kg) or TPM (10, 30, 100 mg/kg). Noxious meningeal stimulation by the irritant capsaicin triggered trigeminovascular system (TGVS) activation mimicking migraine condition, which were assessed peripherally by the depletion of calcitonin gene-related peptide (CGRP) in sensory nerve fibers of the dura mater, the increased CGRP immunoreactivity at trigeminal ganglia (TG) and centrally by the number of c-Fos-immunoreactive (c-Fos-ir) neurons in the trigeminocervical complex (TCC). Peripherally, CGRP released from dural sensory nerve terminals of TG triggered pain signal transmission in the primary afferent of trigeminal nerve, which in turn caused central sensitization of the TGVS due to TCC activation and hence contributed to migraine. Results: In the VPA-treated group, the central responsiveness expressed by reducing the number of c-Fos-ir neurons, which had been increased by i.c. capsaicin, was significant in pediatric, but not adult, rats. Inversely, VPA was effective in peripheral inhibition of elevated CGRP immunoreactivity in the TG and CGRP depletion in the dura mater of adult, but not pediatric, rats. In TPM group, the central responsiveness was significant in both adult and pediatric groups. Peripherally, TPM significantly inhibited capsaicin-induced CGRP expression of TG in adult, but not pediatric, rats. Interestingly, the capsaicin-induced depletion of CGRP in dura was significantly rescued by TPM at high doses in adults, but at low dose in pediatric group. Conclusion: These results suggest VPA exerted peripheral inhibition in adult, but central suppression in pediatric migraine-rats. In contrast, TPM involves both central and peripheral inhibition of migraine with an optimal therapeutic window in both ages. These findings may clarify the age-dependent anti-migraine mechanism of VPA and TPM, which may guide the development of new pediatric anti-migraine drugs in the future.

Matched MeSH terms: Valproic Acid
Fulltext Study of Visual Function in Adult Epileptic Patients on Sodium Valproate or Carbamazepine Monotherapy

Matthew TJH, Tharakan J, Tai E, Hussein A

Cureus, 2019 Apr 27;11(4):e4553.
PMID: 31275777 DOI: 10.7759/cureus.4553

Objective Epilepsy is a debilitating disease. Visual function changes have been reported and may be attributed to the epileptic changes or as a result of medication side effect. Sodium valproate and carbamazepine are both first line anti-epileptic medications used in Malaysian health care. Sodium valproate inhibits glutamate and γ-aminobutyric acid (GABA) transaminase while carbamazepine acts on the sodium channel - both are an important part of the retina. This study aimed to compare the visual functions of epilepsy patients on carbamazepine or sodium valproate monotherapy. Design A cross-sectional study was conducted at a tertiary hospital between June 2016 and November 2018. Methods Patients with idiopathic epilepsy that fulfill the inclusion and exclusion criteria were recruited from the neurology clinic. They were divided into two groups and underwent complete eye examinations. Visual functions such as color vision testing, contrast sensitivity, visual field and retinal nerve fiber layer measurement were subsequently performed. Statistical analysis was done using Statistical Package for the Social Science, version 24 (SPSS Inc, Chicago, IL, USA). Results A total of 100 patients (sodium valproate: 50 patients; carbamazepine: 50 patients) were recruited for the study. There were no statistically significant changes in anatomical or visual function between the sodium valproate and carbamazepine group. However, patients from both groups displayed color vision defect in the blue and green axes. Changes in color vision could indicate early retina toxicity secondary to the medication. Although there were no visual field changes, patients recorded a slight reduction of mean deviation. Changes of mean deviation could be attributed to the side effect of medication or the disease process. Conclusions Epileptic patients taking sodium valproate or carbamazepine did not demonstrate statistically significant change in visual function.

Matched MeSH terms: Valproic Acid
Valproic acid: growth inhibition of head and neck cancer by induction of terminal differentiation and senescence

Gan CP, Hamid S, Hor SY, Zain RB, Ismail SM, Wan Mustafa WM, et al.

Head Neck, 2012 Mar;34(3):344-53.
PMID: 21438066 DOI: 10.1002/hed.21734

There are limited studies on the effects of drugs that modulate epigenetic regulation for head and neck squamous cell carcinoma (HNSCC). This study determined the effect of valproic acid (VPA) on HNSCC.

Matched MeSH terms: Valproic Acid/pharmacology*
Fulltext Lack of association of ABCB1 and PXR polymorphisms with response to treatment in epilepsy

Haerian BS, Lim KS, Mohamed EH, Tan HJ, Tan CT, Raymond AA, et al.

Seizure, 2011 Jun;20(5):387-94.
PMID: 21316268 DOI: 10.1016/j.seizure.2011.01.008

It is proposed that overexpression of P-glycoprotein (P-gp), encoded by the ABC subfamily B member 1 (ABCB1) gene, is involved in resistance to antiepileptic drugs (AEDs) in about 30% of patients with epilepsy. Genetic variation and haplotype patterns are population specific which may cause different phenotypes such as response to AEDs. Although several studies examined the link between the common polymorphisms in the ABCB1 gene with resistance to AEDs, the results have been conflicting. This controversy may be caused by the effect of some confounders such as ethnicity and polytherapy. Moreover, expression of the ABCB1 gene is under the control of pregnane X receptor (PXR). Evidence showed that PXR gene contribute to the response to treatment. The aim of this study was to assess the association of ABCB1 and PXR genetic polymorphisms with response to the carbamazepine (CBZ) or sodium valproate (VPA) monotherapy in epilepsy. Genotypes were assessed in 685 Chinese, Indian, and Malay epilepsy patients for ABCB1 (C1236T, G2677T, C3435T) and PXR (G7635A) polymorphisms. No association between these polymorphisms and their haplotypes, and interaction between them, with response to treatment was observed in the overall group or in the Chinese, Indian, and Malay subgroups. Our data showed that these polymorphisms may not contribute to the response to CBZ or VPA monotherapy treatment in epilepsy.

Matched MeSH terms: Valproic Acid/therapeutic use

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