Acute Disease ; Antimanic Agents ; adverse effects ; Chronic Disease ; Humans ; Pancreatitis ; chemically induced ; Valproic Acid ; adverse effects

Adult ; Afibrinogenemia ; chemically induced ; Humans ; Intracranial Hemorrhages ; chemically induced ; Male ; Valproic Acid ; adverse effects

Anticonvulsants ; adverse effects ; Bone and Bones ; drug effects ; metabolism ; Calcium, Dietary ; administration & dosage ; Humans ; Valproic Acid ; adverse effects ; Vitamin D ; administration & dosage

OBJECTIVETo compare the efficacy of valproic acid (VPA) and lamotrigine as a monotherapy for absence epilepsy in children.

METHODSA randomized, open-label design was used. Childhood absence epilepsy was diagnosed based on the presence of typical seizures and video-EEG findings. Eligible patients were randomly treated with VPA or lamotrigine. All patients were followed up for 12 months.

RESULTSForty-five out of 48 eligible children completed the study. There were 23 children in the VPA group and 22 children in the lamotrigine group. Seventeen children were seizure-free in the VPA group 12 months after treatment. Fifteen out of the 17 children showed normal EEG (no epileptic-formed discharge). Twelve children were seizure-free in the lamotrigine group 12 months after treatment. The proportion showing normal EEG in the lamotrigine group (6/22, 27.3%) was significantly lower than that in the VPA group (15/23, 65.2%) (P<0.05). Severe adverse effects were not found in both groups.

CONCLUSIONSBoth VPA and lamotrigine are safe and efficacious for treatment of absence seizures in children. VPA appears to be better than lamotrigine in tapering epileptic-formed discharge.

Anticonvulsants ; therapeutic use ; Child ; Child, Preschool ; Electroencephalography ; Epilepsy, Absence ; drug therapy ; physiopathology ; Female ; Humans ; Male ; Triazines ; adverse effects ; therapeutic use ; Valproic Acid ; adverse effects ; therapeutic use

OBJECTIVETo investigate the possible role of valproic acid therapy in the development of the weight gain and hyperinsulinemia of epileptic patients.

METHODSThe weight and fasting insulin levels were measured in 43 epileptic patients treated with valproic acid (VPA) alone and 39 patients with carbamazepine (CBZ) alone for at last 2 years. The body mass index (BMI) and homeostasis model assessment (HOMA) index were studied in the two groups.

RESULTBMI was higher in the VPA-treated group (23.47+/-1.45) than that in the CBZ-treated group (22.27+/-2.10, P<0.05). Fasting insulin level and HOMA index in the VPA group were also higher [(6.64+/-0.79)mU/L and 1.33+/-0.21] than those in the CBZ group [(5.52+/- 0.52)mU/L, P<0.01; 1.15+/-0.12, P<0.01]. While BMI in the VPA group showed no significant correlation with plasma concentration and dose of valproate.

CONCLUSIONVPA therapy is associated with significantly greater weight gain and hyperinsulinemia, suggesting development of insulin resistance.

Adult ; Body Mass Index ; Epilepsy ; drug therapy ; metabolism ; Female ; Humans ; Insulin Resistance ; Male ; Valproic Acid ; adverse effects ; Weight Gain ; drug effects

OBJECTIVE: Up to recently, the standard pharmacotherapy of schizophrenia has been monotherapy, use of one antipsychotic medication. However, polypharmacy in patients with schizophrenia is a common practice with little basis in well-controlled studies. In this study, we explored the patterns of pharmacotherapy in inpatient with schizophrenia by comparing prescribed medications at discharge between the year 1997 and the year 2003. METHODS: The medical records of patients who discharged with the diagnosis of schizophrenia from department of psychiatry, St. Mary's hospital in 1997 and 2003 were reviewed. The psychotropic medications at discharge were compared. The length of stay at the hospital and the incidence of adverse drug reactions were also compared. For statistics, chi-square test and independent t-test were performed. RESULTS: Data of 96 patients who discharged in 1997 and 2003 were analyzed. Patients prescribed with more than two kinds of antipsychotics were 7 of 96 in 1997 (7.2%) and 12 of 72 (16.7%), but the difference is not statistically significant (p=0.058). Patients prescribed with antipsychotics and mood stabilizers were 9 (9.3%) in 1997 and 18 (25%) in 2003. The difference is statistically significant (p=0.010). Especially, carbamazepine occupied most part of mood stabilizer use (89%) in 1997 but valproate use was increased much in 2003 (56%). Patients who were administered with anxiolytics (p=0.001) or anti-Parkinson agents (p<0.001) were decreased in 2003 compared with 1997. There were no statistically significant differences in the incidence of adverse drug reactions and the length of stay at the hospital. CONCLUSION: This study found that hospitalized patients with schizophrenia are being treated with more psychotropic medications, including more than 1 antipsychotic.
Anti-Anxiety Agents ; Antipsychotic Agents ; Carbamazepine ; Diagnosis ; Drug Therapy ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Incidence ; Inpatients* ; Length of Stay ; Medical Records ; Polypharmacy* ; Schizophrenia ; Valproic Acid

Toxic epidermal necrolysis is an unpredictable and severe adverse drug reaction. In toxic epidermal necrolysis, epidermal damage appears to result from keratinocyte apoptosis. This condition is triggered by many factors, principally drugs such as antiepileptic medications, antibiotics (particularly sulfonamide), nonsteroidal anti-inflammatory drugs, allopurinol, and nevirapine. Lamotrigine has been reported potentially cause serious cutaneous reactions, and concomitant use of valproic acid with lamotrigine significantly increases this risk. We describe a case of an 11-year-old girl with tic and major depressive disorders who developed toxic epidermal necrolysis after treatment with lamotrigine, and who was diagnosed both clinically and pathologically. Children are more susceptible to lamotrigine-induced rash than adults, and risk of serious rash can be lessened by strict adherence to dosing guidelines. Unfortunately, in our case, the patient was administered a higher dose than the required regimen. Therefore, clinicians should strictly adhere to the dose regimen when using lamotrigine, especially in children.
Adult ; Allopurinol ; Anti-Bacterial Agents ; Apoptosis ; Child* ; Depressive Disorder, Major ; Drug-Related Side Effects and Adverse Reactions ; Exanthema ; Female ; Humans ; Keratinocytes ; Nevirapine ; Stevens-Johnson Syndrome* ; Tics ; Valproic Acid

OBJECTIVEAge, body weight and dose have been shown as important influencing factors for sodium valproate plasma concentrations. However it is unclear whether there is interaction among them and whether the interaction could influence sodium valproate plasma concentrations. This study aimed to evaluate the influence of age, body weight and dose on plasma concentrations of sodium valproate and the interaction among them.

METHODSOne hundred and thirty-two children with epilepsy (age: 4 months-6 years, weight: 5-25 kg) were enrolled. Sodium valproate was administered at the dosage of 10-30 mg/kg/d. Plasma concentrations of sodium valproate were measured by high-performance liquid chromatography 3-5 days after administration. The relationship of sodium valproate plasma concentrations with age, body weight, and dose of sodium valproate was examined using variance analysis, pearson correlation analysis and stepwise regression analysis.

RESULTSAge (F=8.630, P<0.01), body weight (F=3.650, P<0.05) and dose of sodium valproate (F=11.720, P<0.01) were influencing factors for sodium valproate plasma concentrations. The interaction between age and oral dose (F=2.484, P<0.05) and the interaction of age and body weight with oral dose (F=4.923, P<0.01) had significant effects on sodium valproate plasma concentrations. Stepwise regression analysis showed that dose of sodium valproate and body weight were entered to the regression equation.

CONCLUSIONSAge, body weight and dose of sodium valproate as well as the interactions between age and dose and between age, body weight and dose were influencing factors for valproate plasma concentrations.

Age Factors ; Anticonvulsants ; blood ; Body Weight ; Child ; Child, Preschool ; Epilepsy ; drug therapy ; Female ; Humans ; Infant ; Male ; Regression Analysis ; Valproic Acid ; administration & dosage ; adverse effects ; blood

Adverse Event Reporting System (KIDS-KAERS) database, a nationwide database of adverse events reports, between January 2008 and December 2017 to investigate the reporting count of all drug eruptions and calculated the ratio of DRESS/SJS/TEN reports for each AED.RESULTS: Among a total of 2,942 reports, most were of rash/urticaria (2,702, 91.8%), followed by those of DRESS (109, 3.7%), SJS (106, 3.6%), and TEN (25, 0.85%). The common causative AEDs were lamotrigine (699, 23.8%), valproic acid (677, 23%), carbamazepine (512, 17.4%), oxcarbazepine (320, 10.9%), levetiracetam (181, 6.2%), and phenytoin (158, 5.4%). In limited to severe drug eruptions (DRESS, SJS, and TEN; total 241 reports), the causative AEDs were carbamazepine (117, 48.8%), lamotrigine (57, 23.8%), valproic acid (20, 8.3%), phenytoin (15, 6.3%), and oxcarbazepine (10, 4.2%). When comparing aromatic AED with non-aromatic AED, aromatic AEDs were more likely to be associated with severe drug eruption (aromatic AEDs: 204/1,793 versus non-aromatic AEDs: 37/1,149; OR, 3.86; 95% CI, 2.7–5.5). Death was reported in 7 cases; DRESS was the most commonly reported adverse event (n = 5), and lamotrigine was the most common causative AED (n = 5).CONCLUSION: Although most cutaneous drug eruptions in this study were rash or urticaria, approximately 8% of reports were of severe or life-threatening adverse drug reactions, such as SJS, TEN, or DRESS. When hypersensitivity skin reactions occurred, aromatic AEDs were associated with 4 fold the risk of SJS/TEN/DRESS compared with non-aromatic AEDs. Our findings further emphasize that high risk AEDs should be prescribed under careful monitoring, and early detection and prompt interventions are needed to prevent severe complications.]]>
Anticonvulsants ; Carbamazepine ; Drug Eruptions ; Drug Hypersensitivity Syndrome ; Drug-Related Side Effects and Adverse Reactions ; Exanthema ; Hypersensitivity ; Korea ; Pharmacovigilance ; Phenytoin ; Risk Management ; Skin ; Stevens-Johnson Syndrome ; Urticaria ; Valproic Acid

Adolescent ; Anticonvulsants ; adverse effects ; Bone and Bones ; drug effects ; metabolism ; Calcium ; blood ; Calcium, Dietary ; administration & dosage ; Child ; Child, Preschool ; Dietary Supplements ; Epilepsy ; drug therapy ; metabolism ; Female ; Humans ; Male ; Valproic Acid ; adverse effects ; Vitamin D ; administration & dosage