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The efficacy of magnesium oxide and sodium valproate in prevention of migraine headache: a randomized, controlled, double-blind, crossover study.
Karimi, N, Razian, A, Heidari, M
Acta neurologica Belgica. 2021;(1):167-173
Abstract
Migraine is a disabling disorder that affects the quality of life of patients. Different medications have been used in prevention of migraine headache. In this study, we evaluated the effectiveness of magnesium oxide in comparison with valproate sodium in preventing migraine headache attacks. This is a single-center, randomized, controlled, crossover trial which is double-blind, 24-week, 2-sequence, 2-period, 2-treatment. After patient randomization into two sequences, the intervention group received magnesium oxide 500 mg and the control group received valproate sodium 400 mg two tablets each day (every 12 h) for 8 weeks. The primary efficacy variable was reduction in the number of migraine attacks and number of days with moderate or severe headache and hours with headache (duration) per month in the final of 8 weeks in comparison with baseline. Seventy patients were randomized and seven dropped out, leaving 63 for analysis. In an intention-to-treat analysis, 31 patients were in group 1 (magnesium oxide-valproate) and 32 patients were in group 2 (valproate-magnesium oxide). The mean number of migraine attacks and days per month was 1.72 ± 1.18 and 2.09 ± 1.70, with a mean duration of 15.50 ± 21.80 h in magnesium group and 1.27 ± 1.27 and 2.22 ± 1.96, with a mean duration 13.38 ± 14.10 in valproate group. This study has shown that 500 mg magnesium oxide appears to be effective in migraine prophylaxis similar to valproate sodium without significant adverse effect.
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Cinnarizine and sodium valproate as the preventive agents of pediatric migraine: A randomized double-blind placebo-controlled trial.
Amanat, M, Togha, M, Agah, E, Ramezani, M, Tavasoli, AR, Azizi Malamiri, R, Fashandaky, F, Heidari, M, Salehi, M, Eshaghi, H, et al
Cephalalgia : an international journal of headache. 2020;(7):665-674
Abstract
BACKGROUND Few migraine preventive agents have been assessed in a pediatric population. We evaluated the safety and efficacy of cinnarizine and sodium valproate for migraine prophylaxis in children and adolescents. METHODS We carried out a randomized double-blind placebo-controlled trial in the Children's Medical Center and Sina hospital, Tehran, Iran. Eligible participants were randomly assigned in 1:1:1 ratio via interactive web response system to receive either cinnarizine, sodium valproate, or placebo. The primary endpoints were the mean change in frequency and intensity of migraine attacks from baseline to the last 4 weeks of trial. The secondary endpoint was the efficacy of each drug in the prevention of migraine. The drug was considered effective if it decreased migraine frequency by more than 50% in the double-blind phase compared with the baseline. Safety endpoint was adverse effects that were reported by children or their parents. RESULTS A total of 158 children participated. The frequency of migraine attacks significantly reduced compared to baseline in cinnarizine (difference: -8.0; 95% confidence interval (CI): -9.3 to -6.6), sodium valproate (difference: -8.3; 95% confidence interval: -9.3 to -7.2), and placebo (difference: -4.4; 95% confidence interval: -5.4 to -3.4) arms. The decrease was statistically greater in cinnarizine (difference: -3.6; 95% confidence interval: -5.5 to -1.6) and sodium valproate (difference: -3.9; 95% confidence interval: -5.8 to -1.9) arms, compared to placebo group. Children in all groups had significant reduction in intensity of episodes compared to baseline (cinnarizine: -4.6; 95% confidence interval: -5.2 to -4.0; sodium valproate: -4.0; 95% confidence interval: -4.8 to -3.3; placebo: -2.6; 95% confidence interval: -3.4 to -1.8). The decrease was statistically greater in cinnarizine (difference: -2.0; 95% confidence interval: -3.2 to -0.8) and sodium valproate (difference: -1.5; 95% confidence interval: -2.7 to -0.3) arms, compared to the placebo group. Seventy-one percent of individuals in the cinnarizine group, 66% of cases in the sodium valproate group, and 42% of people in the placebo arm reported more than 50% reduction in episodes at the end of the trial. The odds ratio for >50% responder rate was 3.5 (98.3% confidence interval: 1.3 to 9.3) for cinnarizine versus placebo and 2.7 (98.3% confidence interval: 1.0 to 6.9) for sodium valproate versus placebo. Nine individuals reported adverse effects (three in cinnarizine, five in sodium valproate, and one in the placebo group) and one case in the sodium valproate group discontinued the therapy due to severe sedation. CONCLUSION Cinnarizine and sodium valproate could be useful in migraine prophylaxis in children and adolescents. Trial registration: IRCT201206306907N4.
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Assessment of the efficacy of omega-3 fatty acids on metabolic and inflammatory parameters in patients with schizophrenia taking clozapine and sodium valproate.
Behdani, F, Roudbaraki, SN, Saberi-Karimian, M, Tayefi, M, Hebrani, P, Akhavanrezayat, A, Amlashi, SV, Ferns, GA, Ghayour-Mobarhan, M
Psychiatry research. 2018;:243-247
Abstract
Omega-3 fatty acid (FA) supplementation has been reported to improve several cardio-metabolic risk factors. We aimed to assess the efficacy of omega-3 fatty acids on metabolic and inflammatory indices in patients with schizophrenia who were taking clozapine and sodium valproate. All patients were on a stable dose of 300-400mg of clozapine for 3 months. Subjects were randomized to treatment with either omega-3 fatty acid (4gr/day) or a placebo for 8 weeks. Height, weight, abdominal circumference, serum lipid profile, fasting blood glucose (FBG), and serum high sensitivity-C-reactive protein (hs-CRP) were determined at baseline and after 8 weeks of treatment. Fifty six subjects were recruited into the study. Patients with schizophrenia who were in the group receiving omega-3 FA capsules had an improvement in some anthropometric indices including weight, BMI, wrist and waist circumference, compared to the placebo group. Only changes in waist circumferences remained significantly different after adjustment for serum fasted TG. Our results showed omega-3 FA supplementation can improve some anthropometric indices in patients with schizophrenia who are taking clozapine pharmacotherapy.
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Comparing the Effects of Atorvastatin With Sodium Valproate (Divalproex) on Frequency and Intensity of Frequent Migraine Headaches: A Double-blind Randomized Controlled Study.
Hesami, O, Sistanizad, M, Asadollahzade, E, Johari, MS, Beladi-Moghadam, N, Mazhabdar-Ghashghai, H
Clinical neuropharmacology. 2018;(3):94-97
Abstract
OBJECTIVES To evaluate the prophylactic effects of atorvastatin on frequency, intensity, and duration of migraine attacks compared with sodium valproate. METHODS In this randomized, double-blind, single-center controlled trial, patients with 6 to 15 migraine attacks per month, which were candidates of preventive treatment, were recruited. The patients were randomly allocated into 2 groups. The first group (A) received atorvastatin 40 mg daily, and the second group (B) received sodium valproate 500 mg daily. All patients were visited each month and followed up for 3 months. The characteristics of migraine headaches including frequency, intensity, and duration of attacks were recorded, as well as the number of analgesics taken per each attack and probable adverse effects. RESULTS From 100 patients enrolled in the study, 18 cases were excluded owing to adverse effects (2 cases) or lost to follow-up (16 cases). From 82 patients who completed the trial, 46 and 36 were in group A (atorvastatin) and group B (sodium valproate), respectively. Mean age of the patients was not significantly different in the 2 arms of the study (33.56 ± 8.51 in group A and 33.25 ± 9.91 years in group B, P = 0.877). Number, duration, and intensity of attacks and number of analgesics taken during attacks decreased significantly in both groups in monthly follow-ups. However, there was no statistically significant difference between 2 arms of the study in terms of attenuation in the characteristics of migraine attacks. On the other hand, patients in group A suffered fewer adverse effects compared with group B. CONCLUSIONS This study indicates that atorvastatin could be an alternative for sodium valproate in migraine prophylaxis with comparable efficacy and fewer adverse effects. Multicenter studies with larger sample size are recommended.
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Sodium valproate compared to phenytoin in treatment of status epilepticus.
Amiri-Nikpour, MR, Nazarbaghi, S, Eftekhari, P, Mohammadi, S, Dindarian, S, Bagheri, M, Mohammadi, H
Brain and behavior. 2018;(5):e00951
Abstract
BACKGROUND Status epilepticus (SE) is a neurological emergency which can be life-threatening. Several medical regimens are used in order to control it. In this study, we intended to evaluate the clinical efficacy and tolerability of sodium valproate and intravenous phenytoin (IV PHT) in the control of SE. METHODS One hundred and ten consecutive patients suffering from benzodiazepine refractory SE who were referred to the emergency ward from March 2014 to March 2015 were randomly divided into two groups. The first group received intravenous sodium valproate, 30 mg/kg as loading dose and then 4-8 mg/kg every 8 hr as maintenance regimen. The second group received IV PHT 20 mg/kg as loading dose and then 1.5 mg/kg for 8 hr as maintenance therapy. All patients were monitored for vital signs every 2 hr up to 12 hr. The patients were also followed up for 7 days regarding drug response and adverse effects. RESULTS The administration of sodium valproate and phenytoin respectively resulted in seizure control in 43 (78.18%) and 39 (70.90%) of the patients within 7 days of drug administration (p = .428). Seven-day mortality rate was similar in both groups (12.73% vs. 12.73%; p = .612). There was no significant difference in adverse effects between two groups. CONCLUSION Sodium valproate is preferred to IV PHT for treatment and control of SE due to its higher tolerability and lower hemodynamic instability.
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Sodium Valproate, a Histone Deacetylase Inhibitor, Is Associated With Reduced Stroke Risk After Previous Ischemic Stroke or Transient Ischemic Attack.
Brookes, RL, Crichton, S, Wolfe, CDA, Yi, Q, Li, L, Hankey, GJ, Rothwell, PM, Markus, HS
Stroke. 2018;(1):54-61
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BACKGROUND AND PURPOSE A variant in the histone deacetylase 9 (HDAC9) gene is associated with large artery stroke. Therefore, inhibiting HDAC9 might offer a novel secondary preventative treatment for ischemic stroke. The antiepileptic drug sodium valproate (SVA) is a nonspecific inhibitor of HDAC9. We tested whether SVA therapy given after ischemic stroke was associated with reduced recurrent stroke rate. METHODS Data were pooled from 3 prospective studies recruiting patients with previous stroke or transient ischemic attack and long-term follow-up: the South London Stroke Register, The Vitamins to Prevent Stroke Study, and the Oxford Vascular Study. Patients receiving SVA were compared with patients who received antiepileptic drugs other than SVA using survival analysis and Cox Regression. RESULTS A total of 11 949 patients with confirmed ischemic event were included. Recurrent stroke rate was lower in patient taking SVA (17 of 168) than other antiepileptic drugs (105 of 530; log-rank survival analysis P=0.002). On Cox regression, controlling for potential cofounders, SVA remained associated with reduced stroke (hazard ratio=0.44; 95% confidence interval: 0.3-0.7; P=0.002). A similar result was obtained when patients taking SVA were compared with all cases not taking SVA (Cox regression, hazard ratio=0.47; 95% confidence interval: 0.29-0.77; P=0.003). CONCLUSIONS These results suggest that exposure to SVA, an inhibitor of HDAC, may be associated with a lower recurrent stroke risk although we cannot exclude residual confounding in this study design. This supports the hypothesis that HDAC9 is important in the ischemic stroke pathogenesis and that its inhibition, by SVA or a more specific HDAC9 inhibitor, is worthy of evaluation as a treatment to prevent recurrent ischemic stroke.
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A randomized controlled trial of acupressure as an adjunctive therapy to sodium valproate on the prevention of chronic migraine with aura.
Xu, JH, Mi, HY
Medicine. 2017;(27):e7477
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BACKGROUND The primary objective of the present study was to evaluate the efficacy and safety of using acupressure as an adjunctive therapy to sodium valproate (SV) combined with acupressure (ASV) on the prevention of chronic migraine with aura (CMA). METHODS A total of 98 patients with CMA were randomly divided into an intervention group and a control group, with 49 patients in each group. The patients in the intervention group received ASV, while the participants in the control group received SV alone. The primary outcome was measured by the numeric rating scale (NRS). The secondary outcomes including frequency of migraine attacks, the times of using analgesics, and quality of life, measured by the short-form 36 Health Survey Scale (SF-36) score. In addition, adverse events (AEs) were also recorded throughout the trial. The outcomes were measured at the end of the 8-week treatment, and 4-week follow-up. RESULTS After the 8-week treatment and 4-week follow-up, ASV efficacy was not greater than that of SV alone regarding pain relief, as measured using the NRS, and frequency of migraine attacks, consumption of analgesics, and quality of life, as measured using the SF-36. However, ASV can significantly reduce the nausea when compared with SV (P = .04). CONCLUSION The present results indicate that ASV can decrease migraine-related nausea during treatment, but cannot relieve pain or enhance quality of life in patients with CMA.
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The DRD3 Ser9Gly Polymorphism Predicted Metabolic Change in Drug-Naive Patients With Bipolar II Disorder.
Chang, TT, Chen, SL, Chang, YH, Chen, PS, Chu, CH, Chen, SH, Huang, SY, Tzeng, NS, Wang, LJ, Wang, TY, et al
Medicine. 2016;(24):e3488
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Patients with bipolar II disorder (BDII) have a higher prevalence rate of metabolic disturbance. Whether BDII itself, in addition to its current standard treatment, is a risk factor for metabolic syndrome warrants additional study. The dopamine receptor D3 (DRD3) gene, one of the candidate genes for BDII, is also involved in the dopaminergic system. We investigated whether it is related to changes in the metabolic indices of patients with BDII given 12 weeks of standard treatment.Patients with a first diagnosis of BDII (n = 117) were recruited. Metabolic profiles (cholesterol, triglycerides, fasting serum glucose, body mass index) were measured at baseline and at 2, 8, and 12 weeks. The genotype of the DRD3 Ser9Gly polymorphism (rs6280) was determined. Multiple linear regressions with generalized estimating equation methods were used.Seventy-six (65.0%) patients completed the 12-week intervention. Significant differences in triglyceride change were associated with the DRD3 Ser9Gly genotype (P = 0.03). Patients with the Ser/Ser genotype had significantly smaller triglyceride increases and a lower risk of developing metabolic syndrome than did those with the Ser/Gly+Gly/Gly genotype. However, the associations between the DRD3 Ser9Gly polymorphism with changes in triglyceride level become nonsignificant after correcting for multiple comparisons.We conclude that the DRD3 Ser9Gly polymorphism is nominally associated with changes in triglycerides and metabolic syndrome after 12 weeks of standard BDII treatment.
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Comparative effectiveness of levetiracetam, valproate and carbamazepine among elderly patients with newly diagnosed epilepsy: subgroup analysis of the randomized, unblinded KOMET study.
Pohlmann-Eden, B, Marson, AG, Noack-Rink, M, Ramirez, F, Tofighy, A, Werhahn, KJ, Wild, I, Trinka, E
BMC neurology. 2016;(1):149
Abstract
BACKGROUND Few clinical trials have evaluated the efficacy and tolerability of antiepileptic drugs (AEDs) as initial monotherapy for elderly patients. METHODS This post-hoc subgroup analysis of data from an unblinded, randomized, 52-week superiority study (KOMET) compared the effectiveness of levetiracetam (LEV) with extended-release sodium valproate (VPA-ER) and controlled-release carbamazepine (CBZ-CR) as monotherapy in patients aged ≥ 60 years with newly diagnosed epilepsy. The physician chose VPA or CBZ as preferred standard treatment; patients were randomized to standard AEDs or LEV. The primary endpoint was time to treatment withdrawal. Results are exploratory, since KOMET was not powered for a subgroup analysis by age. RESULTS Patients (n = 308) were randomized to LEV (n = 48) or VPA-ER (n = 53) in the VPE-ER stratum or to LEV (n = 104) or CBZ-CR (n = 103) in the CBZ-CR stratum. Mean age was 69.6 years, range 60.2-89.9 years (intention-to-treat population n = 307). Time to treatment withdrawal hazard ratio [HR] (95 % confidence interval [CI]) for LEV vs. standard AEDs was 0.44 (0.28-0.67); LEV vs. VPA-ER: 0.46 (0.16-1.33); LEV vs. CBZ-CR: 0.45 (0.28-0.72). Twelve-month withdrawal rates were: LEV vs. standard AEDs, 20.4 vs. 38.7 %; LEV vs. VPA-ER, 10.4 vs. 23.1 %; LEV vs. CBZ-CR, 25.0 vs. 46.6 %. Time to first seizure was similar between LEV and standard AEDs (HR: 0.92, 95 % CI: 0.63-1.35), LEV and VPA-ER (0.77, 0.38-1.56), and LEV and CBZ-CR (1.02, 0.64-1.63). Adverse events were reported by 76.2, 67.3, and 82.5 % of patients for LEV, VPA-ER, and CBZ-CR, respectively. Discontinuation rates due to AEs were 11.3, 10.2, and 35.0 % for LEV, VPA-ER, and CBZ-CR, respectively. CONCLUSIONS Time to treatment withdrawal was longer with LEV compared with standard AEDs. This finding was driven primarly by the result in the CBZ-CR stratum, which in turn was likely due to the more favorable tolerability profile of LEV. Results of this post-hoc analysis suggest that LEV may be a suitable option for initial monotherapy for patients aged ≥ 60 years with newly diagnosed epilepsy. TRIAL REGISTRATION ClinicalTrials.gov: NCT00175903 ; September 9, 2005.
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Depression and Suicidality Outcomes in the Treatment of Early Age Mania Study.
Salpekar, JA, Joshi, PT, Axelson, DA, Reinblatt, SP, Yenokyan, G, Sanyal, A, Walkup, JT, Vitiello, B, Luby, JL, Wagner, KD, et al
Journal of the American Academy of Child and Adolescent Psychiatry. 2015;(12):999-1007.e4
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OBJECTIVE To assess the efficacy of mood-stabilizing medications for depression and suicidality in pediatric bipolar disorder. METHOD The Treatment of Early Age Mania (TEAM) study is a multicenter, prospective, randomized, masked comparison of divalproex sodium (VAL), lithium carbonate (LI), and risperidone (RISP) in an 8-week parallel clinical trial. A total of 279 children and adolescents with DSM-IV diagnoses of bipolar I disorder, mixed or manic, aged 6 to 15 years were enrolled. The primary outcome measure was improvement on the Clinical Global Impression scale for depression (CGI-BP-I-D). Secondary outcome measures included the Children's Depression Rating Scale (CDRS-R) and suicidality status. Statistics included longitudinal analysis of outcomes using generalized linear mixed models with random intercept both for the complete data set and by using last observation carried forward. RESULTS CGI-BP-I-D ratings were better in the RISP group (60.7%) as compared to the LI (42.2%; p = .03) or VAL (35.0%; p = .003) groups from baseline to the end of the study. CDRS scores in all treatment groups improved equally by study end. In week 1, scores were lower with RISP compared to VAL (mean = 4.72, 95% CI = 2.67, 6.78), and compared to LI (mean = 3.63, 95% CI = 1.51, 5.74), although group differences were not present by the end of the study. Suicidality was infrequent, and there was no overall effect of treatment on suicidality ratings. CONCLUSION Depressive symptoms, present in the acutely manic or mixed phase of pediatric bipolar disorder, improved with all 3 medications, though RISP appeared to yield more rapid improvement than LI or VAL and was superior using a global categorical outcome. Clinical trial registration information-Study of Outcome and Safety of Lithium, Divalproex and Risperidone for Mania in Children and Adolescents (TEAM); http://clinicaltrials.gov; NCT00057681.