Treatment of status epilepticus and acute repetitive seizures with i.v. valproic acid vs phenytoin

Objective – To evaluate the efficacy and tolerability of the treatment with valproic acid (VPA) in patients with status epilepticus (SE) or acute repetitive seizures (ARS) comparing it with phenytoin (PHT) treatment. Materials and methods – Patients with SE or ARS were treated in a consecutive manner with either VPA or PHT intravenously. The primary endpoint was defined as clinical seizure cessation; the secondary endpoint was evaluation of drug tolerability. Results – Seventy‐four adult patients with SE or ARS participated in the study, 49 with VPA i.v. and 25 PHT i.v. In 43 (87.8%) of the VPA patients, the seizures discontinued, and no rescue medication was needed. Similar results were found in the PHT group in which seizures of 22 (88%) patients were well controlled. Side effects were found in 12% of the PHT group, and in none of the VPA group. Conclusions – VPA i.v. seems to be effective and well tolerated in adult patients with SE or ARS.     

An Overview of the Efficacy and Tolerability of New Antiepileptic Drugs

Summary: To evaluate the efficacy and tolerability of recently developed antiepileptic drugs (AEDs), a systematic review of placebo-controlled, randomized controlled trials (RCTs) of the AEDs as add-on therapy in refractory partial epilepsy was conducted. Two or more RCTs meeting our inclusion criteria were found for gabapentin (GBP), lamotrigine (LTG), tiagabine (TGB), topiramate (TPM), vigabatrin (VGB), and zonisamide (ZNS). The outcome selected for estimation of efficacy was the proportion of patients experiencing a ≥50% reduction in seizure frequency from baseline. Tolerability was estimated on the basis of rates of patient withdrawal from study for any reason. Efficacy and tolerability odds ratios (ORs) and 95% confidence intervals (95% CIs) for each measure were generated for each trial included in the analysis, and overall efficacy and tolerability ORs were calculated for each AED across all trials and drug dosages evaluated. Because 95% CIs for both efficacy and tolerability overlapped for the six drugs, conclusive evidence of between-drug differences in effectiveness or safety were not obtained from the analysis. However, the data suggest that the drug with the highest OR for efficacy (TPM) may be approximately twice as effective as the AED with the lowest OR for efficacy (GBP), and that the treatment that appears to most frequently cause withdrawal (ZNS) may be about four times more likely to do so that the AED with the lowest withdrawal rate (LTG). RCTs comparing newer AEDs with the older standard drugs and with each other are needed to further evaluate their relative utility.     

Influence of adjunctive lacosamide in patients with seizures: a systematic review and meta-analysis

Introduction: Adjunctive lacosamide treatment might be promising to treat seizures. However, the results remained controversial. We conducted a systematic review and meta-analysis to compare the efficacy and safety of adjunctive lacosamide versus placebo in patients with seizures.

Methods: PubMed, EMbase, Web of science, EBSCO and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of adjunctive lacosamide versus placebo on seizures were included. Two investigators independently searched articles, extracted data and assessed the quality of included studies. The primary outcomes were 50% responder rate and seizure freedom.

Results: Four RCTs involving 1199 patients were included in the meta-analysis. Overall, compared with placebo treatment, adjunctive lacosamide treatment was associated with a significantly increased 50% responder rate (RR = 1.89; 95% CI = 1.51–2.36; P < 0.00001) and seizure freedom (RR = 4.97; 95% CI = 1.78–13.91; P = 0.002), but improved dizziness (RR = 3.97; 95% CI = 2.91–5.42; P < 0.00001), nausea (RR = 2.85; 95% CI = 1.75–4.66; P < 0.0001), vomiting (RR = 4.11; 95% CI = 2.23–7.57; P < 0.00001), diplopia (RR = 6.85; 95% CI = 3.36–13.94; P < 0.00001), treatment-emergent adverse events (RR = 2.29; 95% CI = 1.93–2.71; P < 0.00001) and serious adverse events (RR = 2.52; 95% CI = 1.33–4.78; P = 0.005).

Conclusions: Compared to placebo, adjunctive lacosamide resulted in a significantly improved 50% responder rate and seizure freedom, but with increased dizziness, nausea, vomiting, diplopia, treatment-emergent adverse events and serious adverse events.     

Intravenous sodium valproate in status epilepticus: review and Meta-analysis

Abstract

Objective: Status epilepticus (SE) is a common neurologic emergency. The present study constitutes a meta-analysis of published randomized control trials (RCTs) evaluating the use of intravenous sodium valproate (VPA) in SE.

Methods: MEDLINE and Cochrane databases were comprehensively searched, while retrieved RCTs and meta-analyses were manually screened. Prespecified outcome measures included seizure-cessation, 24?h-efficacy, constitute (liver enzyme increase, arrhythmias, bone-marrow suppression, hypotension and respiratory depression) and severe (life-threatening) adverse events (AEs). Evidence synthesis was performed when appropriate, using Random-Effects (RE) or Fixed-Effects (FE) model based on heterogeneity between trials (homogeneity assumed when PQ > 0.1 and I² < 50%). Outcomes were assessed using Odds-Ratios (ORs) and 95%Confidence-Intervals (95% CIs). Every available comparison was investigated in terms of efficacy and tolerability.

Results:Thirteen studies were retrieved and five comparisons were available, four of which involved two or more studies. Results were compatible with no significant difference between VPA and Phenytoin both in terms of efficacy and tolerability [seizure-cessation: FE-OR = 1.99, 95% CI = (0.83–4.75), 24?h-efficacy: FE-OR = 1.32, 95% CI = (0.60–2.89), composite AEs: FE-OR = 0.45, 95% CI = (0.17–1.21)]. Phenobarbital proved more commonly associated with composite AEs than VPA [seizure-cessation: RE-OR = 0.68, 95% CI = (0.05–9.44), 24?h-efficacy: RE-OR = 0.88, 95% CI = (0.02–33.9), composite AEs: FE-OR = 0.26, 95% CI = (0.09–0.82), severe AEs: FE-OR = 0.30, 95% CI = (0.04–2.28)]. Diazepam was determined inferior to VPA concerning safety issues [seizure-termination: FE-OR = 0.77, 95% CI = (0.34–1.79), severe respiratory depression: FE-OR = 0.06, 95% CI = (0.01–0.48), severe hypotension: FE-OR = 0.09, 95% CI = (0.01–0.72)]. The combination of Lorazepam (LZP) with VPA and the combination of LZP with Levetiracetam presented no difference in efficacy [24h-efficacy: FE-OR = 0.68, 95% CI = (0.37–1.24)].

Conclusions: Although, additional high-quality RCTs are warranted, according to our results, VPA can be considered a safe and effective option in the management of SE.     

A comparison of four antiepileptic drugs in status epilepticus: experience from India

Purpose: We report the efficacy and safety of lorazepam (LOR), phenytoin (PHT), valproate (VPA) and levetiracetam (LEV) as first and second choice antiepileptic drug (AED) in status epilepticus (SE) and their combinations in preventing refractory SE. Materials and methods: The results of our two earlier trials on SE were compared; one evaluated VPA versus PHT (group I) and the other LOR versus LEV (group II). In group I, additional patients were recruited in addition to published data. The primary outcome was cessation of SE after first and second AEDs and secondary outcome was mortality and side effects. The efficacy of these four drugs as first and second choice was compared. The frequency of refractory seizure in groups I and II and their contributing factors were analyzed. Results: One hundred and seventeen patients were in group I and 79 in group II. The baseline characteristics of the patients were similar in LOR, LEV, VPA and PHT groups. As a first choice, LOR controlled SE in 75.1%, LEV in 76.3%, VPA in 55.4% and PHT in 44.2% patients. As a second choice, LEV was effective in 88.9%, LOR in 70%, VPA in 74.1% and PHT in 25% patients. Refractory SE was more frequent in group I than group II (29.9% versus 10.5%), however, complications and mortality were higher in group II. Conclusion: LOR and LEV combination was superior in reducing refractory SE but at the cost of higher complications and death.     

Thromboprophylaxis in cancer patients with central venous catheters. A systematic review and meta-analysis

It was the aim of the review to determine the risks and benefits of primary thromboprophylaxis with anticoagulants in cancer patients with central venous devices. Medline, Central and Google Scholar databases were searched for randomized controlled trials (RCTs) in June 2006. Two reviewers extracted data and appraised the quality of RCTs. Results were expressed as relative risk (RR) with 95% confidence intervals (CI) using random effects model for the outcomes of catheter-related thrombosis, bleeding and thrombocytopenia. Eight RCTs (1,428 patients) were included. There was no statistically significant difference in the risk of catheter-related thrombosis for the use of warfarin versus placebo (3 trials, 425 patients, RR 0.75, 95% CI 0.24-2.35, p = 0.63), heparin versus placebo (4 trials, 886 patients, RR 0.46 95% CI 0.18-1.20, p = 0.06) or warfarin, unfractionated heparin or low-molecular-weight heparin versus placebo (7 trials, 1,311 patients, RR 0.59, 95% CI 0.31-1.13, p = 0.11). Substantial statistical heterogeneity was noted among these trials (I(2) > 50%). The use of anticoagulants showed no statistically significant difference in the risk of overall bleeding (5 trials, 1,193 patients, RR 1.24, 95% CI 0.84-1.82, p = 0.28), and thrombocytopenia for heparin versus placebo (4 trials, 958 patients, RR 0.85, 95% CI 0.49, 1.46, p = 0.55) without any statistical heterogeneity (I(2) = 0%). In cancer patients with central venous devices, thromboprophylaxis has no significant effect on the risk of catheter related thrombosis or bleeding. The use of primary thromboprophylaxis in cancer patients with central venous catheters while not causing any harm provides no benefit.     

Effectiveness of mood stabilizers and antipsychotics in the maintenance phase of bipolar disorder: a systematic review of randomized controlled trials

BACKGROUND: Bipolar disorder (BD) is a leading cause of disability. Systematic reviews of randomized trials for the treatment of the maintenance phase of BD are lacking. OBJECTIVES: To determine the efficacy and tolerability of mood stabilizers and antipsychotics in the maintenance treatment of BD. METHODS: We systematically reviewed randomized controlled trials of licensed medications for the treatment of any phase of BD. We included randomized controlled trials comparing a medication to placebo or another medication. Comprehensive searches of electronic databases were conducted to March 2005. Outcomes investigated were relapse due to mania, depression or any mood episode, and withdrawal due to any reason or due to an adverse event. Data were combined through meta-analysis. RESULTS: Fourteen studies (n = 2,526) met the inclusion criteria. Lithium, lamotrigine, olanzapine and valproate semisodium each demonstrated evidence to support long-term use. Compared with placebo, all medications were more effective at preventing relapse because of any mood episode. Hazard ratios (HR) were 0.68 [95% confidence interval (CI) = 0.53-0.86] for lithium, 0.68 (95% CI = 0.55-0.85) for lamotrigine, and 0.82 (95% CI = 0.57-1.20) for valproate semisodium; for olanzapine, the risk ratio (RR) was 0.58 (95% CI = 0.49-0.69). Lithium and olanzapine significantly reduced manic relapses (HR = 0.53; 95% CI = 0.35-0.79 and RR = 0.37; 95% CI = 0.24-0.57, respectively). Lamotrigine and valproate semisodium significantly reduced depressive relapses (HR = 0.65; 95% CI = 0.46-0.91 and RR = 0.40; 95% CI = 0.20-0.82, respectively). Lithium significantly reduced manic relapses compared with lamotrigine (HR = 0.56; 95% CI = 0.34-0.92) and olanzapine significantly reduced manic relapses compared with lithium (RR = 1.69; 95% CI = 1.12-2.55). Withdrawal due to an adverse event was approximately twice as likely with lithium compared with valproate semisodium (RR = 1.81; 95% CI = 1.08-3.03) and lamotrigine (RR = 2.20; 95% CI = 1.31-3.70). There were few data for carbamazepine or medications given as adjunct therapy. CONCLUSIONS: Mood stabilizers have differing profiles of efficacy and tolerability, suggesting complementary roles in long-term maintenance treatment.     

Tolerability,safety, and side effects of levetiracetam versus phenytoin in intravenous and total prophylactic regimen among craniotomy patients: A prospective randomized study

Purpose: Practical choice in parenteral antiepileptic drugs (AEDs) remains limited despite formulation of newer intravenous agents and requirements of special patient groups. This study aims to compare the tolerability, safety, and side effect profiles of levetiracetam (LEV) against the standard agent phenytoin (PHT) when given intravenously and in total regimen for seizure prophylaxis in a neurosurgical setting. Methods: This prospective, randomized, single‐center study with appropriate blinding comprised evaluation pertaining to intravenous use 3 days following craniotomy and at discharge, and to total intravenous‐plus‐oral AED regimen at 90 days. Primary tolerability end points were discontinuation because of side effect and first side effect. Safety combined end point was major side effect or seizure. Seizure occurrence and side effect profiles were compared as secondary outcomes. Key Findings: Of 81 patients randomized, 74 (36 LEV, 38 PHT) received parenteral AEDs. No significant difference attributable to intravenous use was found between LEV and PHT in discontinuation because of side effect (LEV 1/36, PHT 2/38, p = 1.00) or number of patients with side effect (LEV 1/36, PHT 4/38, p = 0.36). No significant difference was found between LEV and PHT total intravenous‐plus‐oral regimen in discontinuation because of side effect (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.21–2.92, p = 0.72) or number of patients with side effect (HR 1.51, 95% CI 0.77–2.98, p = 0.22). More patients assigned PHT reached the undesirable clinical end point for safety of major side effect or seizure (HR 0.09, 95% CI 0.01–0.70, p = 0.002). Seizures occurred only in patients assigned PHT (n = 6, p = 0.01). Although not significant, trends were observed for major side effect in more patients assigned PHT (p = 0.08) and mild side effect in more assigned LEV (p = 0.09). Significance: Both LEV and PHT are well‐tolerated perioperatively in parenteral preparation, and in total intravenous‐plus‐oral prophylactic regimen. Comparative safety and differing side effect profile of intravenous LEV supports use as an alternative to intravenous PHT.     

Placebo-corrected efficacy of modern nonenzyme-inducing AEDs for refractory focal epilepsy: systematic review and meta-analysis

Purpose: Given serious concerns over the adverse effects of enzyme induction, modern nonenzyme‐inducing antiepileptic drugs (AEDs) may be preferable, provided they have similar efficacy as enzyme‐inducing AEDs. This is currently unclear. Methods: Therefore, we performed a meta‐analysis of the evidence to determine the placebo‐corrected efficacy of adjunctive treatment with modern nonenzyme‐inducing AEDs versus modern enzyme‐inducing AEDs that are on the market for refractory focal epilepsy. Key Findings: Of 322 potentially eligible articles reviewed in full text, 129 (40%) fulfilled eligibility criteria. After excluding 92 publications, 37 studies dealing with a total of 9,860 patients with refractory focal epilepsy form the basis for the evidence. The overall weighted pooled‐risk ratio (RR) in favor of enzyme‐inducing AEDs over placebo was 2.37 (95% confidence interval [CI] 1.77–3.18, p < 0.001) for at least 50% seizure reduction and 4.45 (2.26–8.76, p < 0.001) for seizure freedom. The corresponding weighted pooled RR in favor of nonenzyme‐inducing AEDs over placebo was 2.28 (95% CI 2.03–2.57, p < 0.001) for at least 50% seizure reduction and 3.23 (95% CI 2.23–4.67, p < 0.001) for seizure freedom. In a meta‐regression analysis in the same sample with at least 50% seizure reduction as outcome, the ratio of RRs for enzyme‐inducing AEDs (eight studies) versus nonenzyme‐inducing AEDs (29 studies) was 1.01 (95% CI 0.77–1.34, p = 0.92)). Similarly, the ratio of RRs for a seizure‐free outcome for enzyme‐inducing AEDs (six studies) versus nonenzyme‐inducing AEDs (19 studies) was 1.38 (95% CI 0.60–3.16, p = 0.43). Significance: Although the presence of moderate heterogeneity may reduce the validity of the results and limit generalizations from the findings, we conclude that the efficacy of adjunctive treatment with modern nonenzyme‐inducing AEDs is similar to that of enzyme‐inducing AEDs. Given the negative consequences of enzyme induction, our data suggest that nonenzyme‐inducing AEDs may be useful alternatives to enzyme‐inducing AEDs for treatment of refractory focal epilepsy.     

Valproate versus diazepam for generalized convulsive status epilepticus: a pilot study

Background and purpose: Evidence‐based data to guide the management of status epilepticus (SE) after failure of primary treatment are still scarce and the alternate needs to be found when phenytoin (PHT) is not available or contraindicated. Comparison of intravenous (IV) valproate (VPA) and diazepam (DZP) infusion has not been conducted in adults with SE. This prospective randomized controlled trial is thus designed to evaluate the relative efficacy and safety of IV VPA and continuous DZP infusion as second‐line anticonvulsants. Methods: After failure of first‐line anticonvulsants treatment, patients with generalized convulsive status epilepticus (GCSE) were randomized to receive either IV VPA or continuous DZP infusion. Primary outcome was the proportion of patients with effective control. Side effects were also evaluated. Results: There were 66 cases enrolled, with the mean age of 41 ± 21 years. Seizure was controlled in 56% (20/36) of the DZP group and 50% (15/30) of the VPA group (P = 0.652). No patient in the VPA group developed respiratory depression, hypotension, or hepatic dysfunction, whereas in the DZP group, 5.5% required ventilation and 5.5% developed hypotension. Time (hour) for regaining consciousness after control was near‐significantly longer in the DZP group [13(3.15–21.5)] than in the VPA group [3(0.75–11)] (P = 0.057). Virus encephalitis and long duration of GCSE were independent risk factors of drug resistance. Conclusions: Both IV VPA and continuous DZP infusion are effective second‐line anticonvulsants for GCSE. IV VPA was well tolerated and free of respiratory depression and hypotension, which may develop in the DZP group. Outcome parameters were not significantly different between groups.     

Efficacy,tolerability, and safety of rapid initiation of topiramate versus phenytoin in patients with new‐onset epilepsy: A randomized double‐blind clinical trial

Purpose: To evaluate topiramate (TPM) and phenytoin (PHT) monotherapy following rapid oral initiation in new‐onset epilepsy. Methods: Randomized, double‐blind, 28‐day trial of TPM (100 mg/day beginning on day 1) versus PHT (1,000 mg on day 1 followed by 300 mg/day maintenance dosing) in 261 patients with new‐onset epilepsy. The primary end point was time to seizure, and the primary objective was to establish noninferiority of TPM to PHT in the risk of seizure. Results: At day 28, the estimated seizure‐free rate was 81.1% for TPM treatment in comparison with 90.3% for PHT treatment. Noninferiority of TPM to PHT (primary objective) could not be established [hazard ratio (HR) 2.0, 95% confidence interval (CI), 0.98 to 4.12, p = 0.366), and PHT could not be shown to be superior to TPM. A higher percentage discontinued with PHT compared to TPM for all reasons (21.1 vs. 12.8%) and due to adverse events (13.4 vs. 6.8%). The most common treatment‐related adverse events in both groups were dizziness, paresthesia, and somnolence. A post hoc analysis showed that TPM was superior to PHT in time to discontinuation (retention rate) for all causes (89.4% vs. 80.3%, p = 0.047). Conclusion: This study was inconclusive in establishing noninferiority of TPM 100 mg/day compared to a standard regimen of oral PHT in seizure risk in this population of patients with new‐onset epilepsy. Given the superiority of TPM in overall retention and favorable tolerability without titration, it may nonetheless be an appropriate option in some patients with new‐onset epilepsy requiring rapid treatment initiation.     

Valproate in the Treatment of Partial Epilepsies

Summary: Review of randomized controlled trials (RCTs) shows that valproate (VPA) is effective against partial seizures with or without becoming secondarily generalized. A number of RCTs show little difference in the efficacy of VPA and carbamazepine in this patient group, particularly where patients are randomized at the time of diagnosis. The length of time that it has taken to arrive at these conclusions emphasizes the importance of large active-controlled RCTs at an early stage in drug development in informing clinical practice.     

Sodium valproate versus lamotrigine: a randomised comparison of efficacy, tolerability and effects on circulating androgenic hormones in newly diagnosed epilepsy

We have performed a randomised, prospective study to compare the efficacy and tolerability of sodium valproate (VPA) and lamotrigine (LTG) monotherapy, and their effects on circulating androgenic hormones, in newly diagnosed epilepsy. A total of 225 patients (116 male; median age 35 years, range 13-80 years) were followed-up at 6-weekly intervals until they reached an end-point (12 months' seizure freedom; withdrawal due to intolerable side-effects; lack of efficacy despite adequate dosing). Twelve month seizure-free rates were identical (47%) in the VPA (n=111) and LTG (n=114) treatment arms. More patients taking VPA withdrew from the study due to adverse events (26 VPA versus 15 LTG; p=0.046). Eight patients, all taking VPA, dropped out during the first 6 months due to weight gain. There were no changes in mean serum concentrations of testosterone, sex-hormone binding globulin and androstenedione or in the free androgen index after 6 or 12 months' treatment with either drug in 112 patients who fulfilled the criteria for hormone analysis. No difference in efficacy was found between VPA and LTG in our patients with newly diagnosed epilepsy. LTG appeared to be better tolerated. Neither drug appeared to alter the circulating levels of androgenic hormones.     

Comparison of the efficacy and safety of levetiracetam and phenytoin in the treatment of established status epilepticus: A systematic review and meta-analysis

Status epilepticus (SE) is the second most critical neurological illness after cerebrovascular disease. Phenytoin has traditionally been considered the second-line drug of first choice after failure of first-line treatment using benzodiazepines. In recent years, levetiracetam has been proposed as a potential substitute for phenytoin. To comprehensively evaluate the efficacy and safety of levetiracetam and phenytoin in the treatment of patients with established SE, we integrated the data from 11 eligible studies and conducted a systematic review and meta-analysis. The PubMed, Web of Science, Cochrane Library, and Embase databases were searched to identify eligible articles reporting outcomes including clinical seizure cessation within 60 min, clinical recurrence rate within 24 h, good final outcome at discharge, and adverse events (AEs) of treatment with levetiracetam and phenytoin. Our study included a total of 11 trials including a total of 1933 patients. The outcomes showed that the pooled Risk Raito (RR) of clinical seizure cessation within 60 min was 1.08 (95% CI = 1.02–1.14, P = 0.01). The pooled RR of clinical recurrence rate within 24 h was 1.03 (95% CI = 0.66–1.59, P = 0.91). The pooled RR of AEs was 0.83 (95% CI = 0.57–1.21, P = 0.34). The pooled RRs of life-threatening hypotension and acute respiratory depression were 0.29 (95% CI = 0.10–0.81, P = 0.02) and 0.63 (95% CI = 0.40–0.98, P = 0.04), respectively. Levetiracetam might be more effective than phenytoin for the treatment of established SE and is associated with a lower incidence of more serious AEs. Levetiracetam can be used as an alternative to phenytoin for the treatment of benzodiazepine-refractory SE.     

Efficacy and Adverse Effects of Established and New Antiepileptic Drugs*

Summary: Antiepileptic drug (AED) selection is based primarily on efficacy for specific seizure types and epileptic syndromes. However, efficacy is often similar for the different AEDs, and other properties such as adverse effects, pharmacokinetic properties, and cost may also be of importance. For idiopathic generalized epilepsies with absence, tonic-clonic, and myoclonic seizures, the AED of choice is valproate (VPA). Secondarily generalized epilepsies with tonic, atonic, and other seizure types are difficult to treat with any single AED or combination of AEds. The AEDs of choice for absence seizures are ethosuximide (ESM) and VPA. For control of primary generalized tonic-clonic seizures, any of the other major AEDs can be effective. If VPA cannot be prescribed, carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), or primidone (PRM) may be effective, but ESM or a benzodiazepine (BZD) must be added to control associated absence or myoclonic seizures. The AEDs of first choice for partial epilepsies with partial and secondarily generalized tonic-clonic seizures are CBZ and PHT. Increasing evidence suggests that VPA is a good alternative when CBZ and PHT fail. PB and PRM are second-choice selections because of adverse effects. A combination of two of the five standard AEDs may be necessary to treat intractable seizures, but no studies have been done to indicate an optimal combination. Other epilepsy syndromes such as neonatal and infantile epilepsies, febrile epilepsy, alcoholic epilepsy, and status epilepticus require specific AED treatment. Ultimately, AED selection must be individualized. No “drug of choice” can be named for all patients. The expected efficacy for the seizure type, the importance of the expected adverse effects, the pharmacokinetics, and the cost of the AEDs all must be weighed and discussed with the patient before a choice is made. A number of new AEDs with unique mechanisms of action, pharmacokinetic properties, and fewer adverse effects hold important promise of improved epilepsy treatment.     

Efficacy and tolerability of antiepileptic drugs in an Omani epileptic population

OBJECTIVE: The aim of this hospital-based study is to get an insight into the efficacy and tolerability of antiepileptic drugs (AED) in Omani epileptic patients. PATIENTS AND METHODS: All Omani patients (aged 14 years and above) suffering from epileptic seizures for at least 2 years and followed-up by board-certified neurologists in Sultan Qaboos University Hospital (SQUH) were evaluated. The treatment retention rate since first visit at SQUH and over the last 2 years was used as primary efficacy measure of AED therapy. Change in seizure-frequency and side effect profiles were also assessed. RESULTS: In this population of 203 confirmed epileptic patients, generalized tonic-clonic (40%) and partial seizures (39%) were most commonly observed, idiopathic/cryptogenic origin (81%) being the most frequent encountered origin. Sixty one percent of the patients were controlled with an AED in monotherapy and overall 34% of patients could be successfully maintained on monotherapy during the whole follow-up period at SQUH (median 6 years). The treatment retention rates for carbamazepine (CBZ) at a daily dose of 400-600 mg, sodium valproate (VPA) at a daily dose of 500-1000 mg, and phenytoin (PHT) at a daily dose of 300 mg, in monotherapy over the total follow-up period was 51, 50, and 21%, respectively. In contrast, over the last 2 years these rates were highest for VPA (91%) followed by CBZ (83%) and PHT (73%). Adverse drug reactions were recorded in 67% of patients, and were most commonly encountered with VPA. CONCLUSIONS: Despite a higher adverse effect profile for VPA, long-term treatment with CBZ and VPA appeared to be equally effective in terms of treatment retention rates and seizure control.     

Meta-Analysis: Efficacy and Tolerability of Vesicular Monoamine Transporter Type 2 Inhibitors in the Treatment of Tic Disorders

Vesicular monoamine transporter type 2 (VMAT2) inhibitors may be an effective therapy for chronic tic disorders (CTD), including Tourette syndrome (TS), but there has not been a meta-analysis compiling available evidence from randomized controlled trials (RCTs). We performed a systematic review and meta-analysis to evaluate the efficacy, acceptability, and tolerability of VMAT2 inhibitors for CTD/TS. PubMed, CENTRAL, and Embase were searched for double-blinded RCTs of VMAT2 inhibitors versus placebo for the treatment of CTD/TS. Change in tic severity measured by the Yale Global Tic Severity Scale (efficacy) and rates of discontinuation attributed to adverse effects (tolerability) or all causes (acceptability) were extracted closest to 12 weeks. Mean difference (MD) and odds ratio (OR) were the effect size indexes for efficacy and acceptability/tolerability, respectively. Data were pooled through random-effects meta-analysis weighted by inverse variance. Five RCTs involving eight comparisons were included. Meta-analysis found a nonsignificant effect on efficacy (k = 8; N = 583; MD = −0.71; 95% confidence interval [CI], −1.93 to 0.50; P = 0.24), and there was certainty that the true effect is nonclinically meaningful (high quality of evidence). Meta-analysis found decreased tolerability (k = 7; N = 626; OR = 2.67; 95% CI, 1.21–5.92; P = 0.01) and decreased acceptability (k = 8; N = 626; OR = 1.90; 95% CI, 1.14–3.18; P = 0.01), although those comparisons were limited because of the relatively small number of events across trials. Meta-analyses did not support the efficacy of VMAT2 inhibitors in the short-term treatment of tic disorders and suggested no clinically meaningful effect of these agents on tic symptoms. © 2022 International Parkinson and Movement Disorder Society     

Efficacy and Safety of Citalopram for the Treatment of Poststroke Depression: A Meta­Analysis

Objective

To objectively evaluate the efficacy and safety of citalopram versus other antidepressant drugs in poststroke depression (PSD) treatment.

Nonintravenous midazolam versus intravenous or rectal diazepam for the treatment of early status epilepticus: A systematic review with meta-analysis

BackgroundPrompt treatment of status epilepticus (SE) is associated with better outcomes. Rectal diazepam (DZP) and nonintravenous (non-IV) midazolam (MDZ) are often used in the treatment of early SE instead of intravenous applications. The aim of this review was to determine if nonintravenous MDZ is as effective and safe as intravenous or rectal DZP in terminating early SE seizures in children and adults.MethodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and MEDLINE for randomized controlled trials comparing non-IV MDZ with DZP (by any route) in patients (all ages) with early SE defined either as seizures lasting > 5 min or as seizures at arrival in the emergency department. The following outcomes were assessed: clinical seizure cessation within 15 min of drug administration, serious adverse effects, time interval to drug administration, and time from arrival in the emergency department to seizure cessation. Outcomes were assessed using a random-effects Mantel–Haenszel meta-analysis to calculate risk ratio (RR), odds ratio (OR) and mean difference with 95% confidence intervals (95% CIs).ResultsNineteen studies with 1933 seizures in 1602 patients (some trials included patients with more than one seizure) were included. One thousand five hundred seventy-three patients were younger than 16 years. For seizure cessation, non-IV MDZ was as effective as DZP (any route) (1933 seizures; RR: 1.03; 95% CIs: 0.98 to 1.08). No difference in adverse effects was found between non-IM MDZ and DZP by any route (1933 seizures; RR: 0.87; 95% CIs: 0.50 to 1.50). Time interval between arrival and seizure cessation was significantly shorter with non-IV MDZ by any route than with DZP by any route (338 seizures; mean difference: − 3.67 min; 95% CIs: − 5.98 to − 1.36); a similar result was found for time from arrival to drug administration (348 seizures; mean difference: − 3.56 min; 95% CIs: − 5.00 to − 2.11). A minimal difference was found for time interval from drug administration to clinical seizure cessation, which was shorter for DZP by any route than for non-IV MDZ by any route (812 seizures; mean difference: 0.56 min; 95% CIs: 0.15 to 0.98 min). Not all studies reported information on time intervals. Comparison by each way of administration failed to find a significant difference in terms of clinical seizure cessation and occurrence of adverse effects. The only exception was the comparison between buccal MDZ and rectal DZP, where MDZ was more effective than rectal DZP in terminating SE but only when results were expressed as OR (769 seizures; OR: 1.78; 95% CIs: 1.11 to 2.85; RR: 1.15; 95% CIs: 0.85 to 1.54). Only one study was entirely conducted in an adult population (21 patients, aged 31 to 69 years), showing no difference in efficacy or time to seizure cessation after drug administration between intranasal MDZ and rectal DZP.ConclusionsNon-IV MDZ is as effective and safe as intravenous or rectal DZP in terminating early SE in children and probably also in adults. Times from arrival in the emergency department to drug administration and to seizure cessation are shorter with non-IV MDZ than with intravenous or rectal DZP, but this does not necessarily result in higher seizure control. An exception may be the buccal MDZ, which, besides being socially more acceptable and easier to administer, might also have a higher efficacy than rectal DZP in seizure control.This article is part of a Special Issue entitled Status Epilepticus.     

The role of vitamin E (tocopherol) supplementation in the prevention of stroke. A meta-analysis of 13 randomised controlled trials

It was the objective of this work to systematically evaluate the role of vitamin E supplementation in the prevention of stroke. Eligible studies were identified from Medline, Embase and Cochrane Library. The efficacy data is the relative risk (RR) for the events of stroke. Thirteen randomised controlled trials (RCTs), with 166,282 participants in total, were analysed. The pooled results showed no significant benefit in the vitamin E group with respect to stroke of any type (RR 1.01; 95% confidence interval [CI]: 0.96, 1.07); ischaemic stroke (RR 1.01; 95% CI: 0.94, 1.09), haemorrhagic stroke (RR 1.12; 95% CI: 0.94, 1.33), fatal stroke (RR 0.94; 95% CI: 0.77, 1.14), and non-fatal stroke (RR 0.99; 95% CI: 0.91, 1.08). Administration of vitamin E 300 IU/day or more also gain no benefit (RR 0.99; 95% CI: 0.92, 1.06), as well as vitamin E less than 300 IU (RR 1.05; 95% CI: 0.96, 1.15). Vitamin E supplementation gained benefit of preventing stroke for neither healthy people (0.92; 0.83, 1.03) nor others at high risks in baseline (RR 1.05; 95% CI: 0.98, 1.12). Administration of synthetic vitamin E gain no benefit (RR 1.02; 95% CI: 0.96, 1.09), as well as the natural source vitamin E (RR 0.99; 95% CI: 0.89, 1.09). In conclusion, there is a lack of statistically significant or clinically important benefit of vitamin E supplementation in the prevention of stroke.