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Clinical Toxicology (Philadelphia, Pa.) Jun 2015The EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup presents its systematic review and clinical recommendations on the use of extracorporeal treatment (ECTR)... (Review)
Review
BACKGROUND
The EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup presents its systematic review and clinical recommendations on the use of extracorporeal treatment (ECTR) in valproic acid (VPA) poisoning.
METHODS
The lead authors reviewed all of the articles from a systematic literature search, extracted the data, summarized the key findings, and proposed structured voting statements following a predetermined format. A two-round modified Delphi method was chosen to reach a consensus on voting statements and the RAND/UCLA Appropriateness Method was used to quantify disagreement. Anonymous votes were compiled, returned, and discussed in person. A second vote was conducted to determine the final workgroup recommendations.
RESULTS
The latest literature search conducted in November 2014 retrieved a total of 79 articles for final qualitative analysis, including one observational study, one uncontrolled cohort study with aggregate analysis, 70 case reports and case series, and 7 pharmacokinetic studies, yielding a very low quality of evidence for all recommendations. Clinical data were reported for 82 overdose patients while pharmaco/toxicokinetic grading was performed in 55 patients. The workgroup concluded that VPA is moderately dialyzable (level of evidence = B) and made the following recommendations: ECTR is recommended in severe VPA poisoning (1D); recommendations for ECTR include a VPA concentration > 1300 mg/L (9000 μmol/L)(1D), the presence of cerebral edema (1D) or shock (1D); suggestions for ECTR include a VPA concentration > 900 mg/L (6250 μmol/L)(2D), coma or respiratory depression requiring mechanical ventilation (2D), acute hyperammonemia (2D), or pH ≤ 7.10 (2D). Cessation of ECTR is indicated when clinical improvement is apparent (1D) or the serum VPA concentration is between 50 and 100 mg/L (350-700 μmol/L)(2D). Intermittent hemodialysis is the preferred ECTR in VPA poisoning (1D). If hemodialysis is not available, then intermittent hemoperfusion (1D) or continuous renal replacement therapy (2D) is an acceptable alternative.
CONCLUSIONS
VPA is moderately dialyzable in the setting of overdose. ECTR is indicated for VPA poisoning if at least one of the above criteria is present. Intermittent hemodialysis is the preferred ECTR modality in VPA poisoning.
Topics: Anticonvulsants; Drug Overdose; Hemoperfusion; Humans; Poisoning; Renal Dialysis; Treatment Outcome; Valproic Acid
PubMed: 25950372
DOI: 10.3109/15563650.2015.1035441 -
Seizure Nov 2022Multiple interventions have been studied for benzodiazepine-resistant status epilepticus (SE) in children and adults. This review aimed to summarize the available... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Multiple interventions have been studied for benzodiazepine-resistant status epilepticus (SE) in children and adults. This review aimed to summarize the available evidence and provide estimates of comparative effectiveness and ranking of treatment effects.
METHODS
All randomized controlled trials studying patients (>1 month of age) with benzodiazepine-resistant SE were included. Outcomes including seizure cessation within 60 min, seizure freedom for 24 h, death, respiratory depression warranting intubation and cardiovascular instability were studied. Conventional and network meta-analyses (NMA) were done.
RESULTS
Seventeen studies were included (16 in NMA). Phenobarbital and high-dose levetiracetam were significantly superior to phenytoin with respect to seizure cessation within 60 min. Network ranking demonstrated that phenobarbital had the highest probability of being the best among the studied interventions followed by high-dose levetiracetam and high-dose valproate. Network meta-analysis was limited by predominant indirect evidence and high heterogeneity.On pairwise comparisons, phenobarbital was found to be associated with a higher risk of need for intubation and cardiovascular instability. Levetiracetam had a better safety profile than fosphenytoin.
CONCLUSIONS
Based on low quality evidence, phenobarbital appears to be the most effective agent for seizure cessation within 60 min of administration in patients with benzodiazepine resistant status epilepticus. High-dose levetiracetam, high-dose valproate and fosphenytoin are probably equally effective. Choice of medication may be guided by effectiveness, safety concerns, availability, cost and systemic co-morbidities.
Topics: Adult; Child; Humans; Anticonvulsants; Benzodiazepines; Levetiracetam; Network Meta-Analysis; Phenobarbital; Phenytoin; Seizures; Status Epilepticus; Valproic Acid; Drug Resistance; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 36209676
DOI: 10.1016/j.seizure.2022.09.017 -
The Journal of Headache and Pain May 2023While there are several trials that support the efficacy of various drugs for migraine prophylaxis against placebo, there is limited evidence addressing the comparative... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
While there are several trials that support the efficacy of various drugs for migraine prophylaxis against placebo, there is limited evidence addressing the comparative safety and efficacy of these drugs. We conducted a systematic review and network meta-analysis to facilitate comparison between drugs for migraine prophylaxis.
METHODS
We searched MEDLINE, EMBASE, CENTRAL, and clinicaltrials.gov from inception to August 13, 2022, for randomized trials of pharmacological treatments for migraine prophylaxis in adults. Reviewers worked independently and in duplicate to screen references, extract data, and assess risk of bias. We performed a frequentist random-effects network meta-analysis and rated the certainty (quality) of evidence as either high, moderate, low, or very low using the GRADE approach.
RESULTS
We identified 74 eligible trials, reporting on 32,990 patients. We found high certainty evidence that monoclonal antibodies acting on the calcitonin gene related peptide or its receptor (CGRP(r)mAbs), gepants, and topiramate increase the proportion of patients who experience a 50% or more reduction in monthly migraine days, compared to placebo. We found moderate certainty evidence that beta-blockers, valproate, and amitriptyline increase the proportion of patients who experience a 50% or more reduction in monthly migraine days, and low certainty evidence that gabapentin may not be different from placebo. We found high certainty evidence that, compared to placebo, valproate and amitriptyline lead to substantial adverse events leading to discontinuation, moderate certainty evidence that topiramate, beta-blockers, and gabapentin increase adverse events leading to discontinuation, and moderate to high certainty evidence that (CGRP(r)mAbs) and gepants do not increase adverse events.
CONCLUSIONS
(CGRP(r)mAbs) have the best safety and efficacy profile of all drugs for migraine prophylaxis, followed closely by gepants.
Topics: Adult; Humans; Topiramate; Valproic Acid; Gabapentin; Calcitonin Gene-Related Peptide; Network Meta-Analysis; Amitriptyline; Antibodies, Monoclonal; Migraine Disorders
PubMed: 37208596
DOI: 10.1186/s10194-023-01594-1 -
European Journal of Investigation in... Aug 2023This review aimed to investigate the metabolic alterations associated with psychopharmacological treatment of neuropsychiatric disorders, which can significantly impact... (Review)
Review
This review aimed to investigate the metabolic alterations associated with psychopharmacological treatment of neuropsychiatric disorders, which can significantly impact patients' physical health and overall quality of life. The study utilized the PRISMA methodology and included cross-sectional, retrospective studies, and randomized clinical trials from reputable databases like SCOPUS, CLARIVATE, SCIENCE DIRECT, and PUBMED. Out of the 64 selected studies, various psychotropic drug classes were analyzed, including antidepressants, anticonvulsants, and antipsychotics. Among the antidepressants, such as amitriptyline, Imipramine, and clomipramine, weight gain, constipation, and cardiovascular effects were the most commonly reported metabolic adverse effects. SSRI antidepressants like Fluoxetine, Sertraline, Citalopram, Escitalopram, and Paroxetine exhibited a high prevalence of gastrointestinal and cardiac alterations. Regarding anticonvulsants, valproic acid and Fosphenytoin were associated with adverse reactions such as weight gain and disturbances in appetite and sleep patterns. As for antipsychotics, drugs like Clozapine, Olanzapine, and Risperidone were linked to weight gain, diabetes, and deterioration of the lipid profile. The findings of this review emphasize the importance of continuous monitoring for adverse effects, particularly considering that the metabolic changes caused by psychopharmacological medications may vary depending on the age of the patients. Future research should focus on conducting field studies to further expand knowledge on the metabolic effects of other commonly prescribed psychotropic drugs. Overall, the study highlights the significance of understanding and managing metabolic alterations induced by psychopharmacological treatment to enhance patient care and well-being.
PubMed: 37623307
DOI: 10.3390/ejihpe13080110 -
BMJ Open Jul 2017Compare the safety of antiepileptic drugs (AEDs) on neurodevelopment of infants/children exposed in utero or during breast feeding. (Meta-Analysis)
Meta-Analysis Review
Comparative safety of antiepileptic drugs for neurological development in children exposed during pregnancy and breast feeding: a systematic review and network meta-analysis.
OBJECTIVES
Compare the safety of antiepileptic drugs (AEDs) on neurodevelopment of infants/children exposed in utero or during breast feeding.
DESIGN AND SETTING
Systematic review and Bayesian random-effects network meta-analysis (NMA). MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched until 27 April 2017. Screening, data abstraction and quality appraisal were completed in duplicate by independent reviewers.
PARTICIPANTS
29 cohort studies including 5100 infants/children.
INTERVENTIONS
Monotherapy and polytherapy AEDs including first-generation (carbamazepine, clobazam, clonazepam, ethosuximide, phenobarbital, phenytoin, primidone, valproate) and newer-generation (gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate, vigabatrin) AEDs. Epileptic women who did not receive AEDs during pregnancy or breast feeding served as the control group.
PRIMARY AND SECONDARY OUTCOME MEASURES
Cognitive developmental delay and autism/dyspraxia were primary outcomes. Attention-deficit hyperactivity disorder, language delay, neonatal seizures, psychomotor developmental delay and social impairment were secondary outcomes.
RESULTS
The NMA on cognitive developmental delay (11 cohort studies, 933 children, 18 treatments) suggested that among all AEDs only valproate was statistically significantly associated with more children experiencing cognitive developmental delay compared with control (OR=7.40, 95% credible interval (CrI) 3.00 to 18.46). The NMA on autism (5 cohort studies, 2551 children, 12 treatments) suggested that oxcarbazepine (OR 13.51, CrI 1.28 to 221.40), valproate (OR 17.29, 95% CrI 2.40 to 217.60), lamotrigine (OR 8.88, CrI 1.28 to 112.00) and lamotrigine+valproate (OR 132.70, CrI 7.41 to 3851.00) were associated with significantly greater odds of developing autism compared with control. The NMA on psychomotor developmental delay (11 cohort studies, 1145 children, 18 treatments) found that valproate (OR 4.16, CrI 2.04 to 8.75) and carbamazepine+phenobarbital+valproate (OR 19.12, CrI 1.49 to 337.50) were associated with significantly greater odds of psychomotor delay compared with control.
CONCLUSIONS
Valproate alone or combined with another AED is associated with the greatest odds of adverse neurodevelopmental outcomes compared with control. Oxcarbazepine and lamotrigine were associated with increased occurrence of autism. Counselling is advised for women considering pregnancy to tailor the safest regimen.
TRIAL REGISTRATION NUMBER
PROSPERO database (CRD42014008925).
Topics: Anticonvulsants; Autistic Disorder; Bayes Theorem; Breast Feeding; Carbamazepine; Child; Epilepsy; Female; Humans; Lamotrigine; Observational Studies as Topic; Oxcarbazepine; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Triazines; Valproic Acid
PubMed: 28729328
DOI: 10.1136/bmjopen-2017-017248 -
Journal of Neurology Oct 2023To compare the efficacy and safety of antiseizure medications (ASMs), both as monotherapies and adjunctive therapies, for idiopathic generalized epilepsies (IGEs) and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To compare the efficacy and safety of antiseizure medications (ASMs), both as monotherapies and adjunctive therapies, for idiopathic generalized epilepsies (IGEs) and related entities.
METHODS
Two reviewers independently searched PubMed, Embase, and the Cochrane Library for relevant randomized controlled trials from December 2022 to February 2023. Studies on the efficacy and safety of ASM monotherapies or adjunctive therapies for IGEs and related entities-including juvenile myoclonic epilepsy, childhood absence epilepsy (CAE), juvenile absence epilepsy, or generalized tonic-clonic seizures alone (GTCA)-were included. Efficacy outcomes were the proportions of patients remaining seizure free for 1, 3, 6, and 12 months; safety outcomes were the proportions of any treatment-emergent adverse event (TEAE) and TEAEs leading to discontinuation. Network meta-analyses were performed in a random-effects model to obtain odds ratios and 95% confidence intervals. Rankings of ASMs were based on the surface under the cumulative ranking curve (SUCRA). This study is registered with PROSPERO (No. CRD42022372358).
RESULTS
Twenty-eight randomized controlled trials containing 4282 patients were included. As monotherapies, all ASMs were more effective than placebo, and valproate and ethosuximide were significantly better than lamotrigine. According to the SUCRA for efficacy, ethosuximide ranked first for CAE, whereas valproate ranked first for other types of IGEs. As adjunctive therapies, topiramate ranked best for GTCA as well as overall for IGEs, while levetiracetam ranked best for myoclonic seizures. For safety, perampanel ranked best (measured by any TEAE).
CONCLUSIONS
All of the studied ASMs were more effective than placebo. Valproate monotherapy ranked best overall for IGEs, whereas ethosuximide ranked best for CAE. Adjunctive topiramate and levetiracetam were most effective for GTCA and myoclonic seizures, respectively. Furthermore, perampanel had the best tolerability.
Topics: Humans; Child; Valproic Acid; Topiramate; Network Meta-Analysis; Levetiracetam; Ethosuximide; Anticonvulsants; Epilepsy, Generalized; Seizures; Randomized Controlled Trials as Topic
PubMed: 37378757
DOI: 10.1007/s00415-023-11834-8 -
Pediatric Nephrology (Berlin, Germany) Jun 2023Valproic acid is prescribed for epilepsy and as prophylaxis for bipolar disorder and migraine headaches. It has also been implicated as a cause of a kidney tubular... (Review)
Review
BACKGROUND
Valproic acid is prescribed for epilepsy and as prophylaxis for bipolar disorder and migraine headaches. It has also been implicated as a cause of a kidney tubular injury.
METHODS
We undertook a review of the literature to characterize the biochemical and histopathological features of the overt kidney tubular injury and to evaluate the possible existence of a pauci-symptomatic injury. The pre-registered review (CRD42022360357) was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Searches were conducted in Excerpta Medica, the National Library of Medicine, and Web of Science. The gray literature was also considered.
RESULTS
For the final analysis, we retained 36 articles: 28 case reports documented 48 individuals with epilepsy on valproic acid for 7 months or more and presenting with features consistent with an overt kidney tubular injury. The following disturbances were noted: hypophosphatemia (N = 46), normoglycemic glycosuria (N = 46), total proteinuria (N = 45), metabolic acidosis (N = 36), hypouricemia (N = 27), tubular proteinuria (N = 27), hypokalemia (N = 23), and hypocalcemia (N = 8). A biopsy, obtained in six cases, disclosed altered proximal tubular cells with giant and dysmorphic mitochondria. Eight case series addressed the existence of a pauci- or even asymptomatic kidney injury. In the reported 285 subjects on valproic acid for 7 months or more, an isolated tubular proteinuria, mostly N-acetyl-β-glucosaminidase, was often noted.
CONCLUSIONS
Valproic acid may induce an overt kidney tubular injury, which is associated with a proximal tubular mitochondrial toxicity. Treatment for 7 months or more is often associated with a pauci- or oligosymptomatic kidney tubular injury. A higher resolution version of the Graphical abstract is available as Supplementary information.
Topics: Humans; Valproic Acid; Kidney Tubules, Proximal; Kidney; Proteinuria; Epilepsy
PubMed: 36645492
DOI: 10.1007/s00467-022-05869-8 -
Journal of Affective Disorders Aug 2022Rapid cycling is a phase of bipolar disorder with increased episode frequencies. It is a severe and disabling condition that often poses a major challenge to the... (Review)
Review
OBJECTIVES
Rapid cycling is a phase of bipolar disorder with increased episode frequencies. It is a severe and disabling condition that often poses a major challenge to the clinician. The aim of this paper is to give an overview of the evidence-based treatment options for rapid cycling.
METHODS
A systematic search on Pubmed, Embase and Cochrane databases from inception until December 2021 was conducted according to the PRISMA guidelines. An additional search on clinicaltrials.gov was done. References of retrieved papers and key reviews were hand-searched. Randomized controlled trials including at least 10 patients with bipolar disorder, rapid cycling, reporting an objective outcome measure were selected.
RESULTS
Our search, initially revealing 1330 articles, resulted in 16 papers about treatment of an acute mood episode, relapse prevention or both. Lithium, anticonvulsants, second generation antipsychotics, antidepressants and thyroid hormone were assessed as treatment options in the presented data. Evidence supporting the use of aripiprazole, olanzapine, quetiapine, valproate and lamotrigine for treatment of rapid cycling bipolar disorder was found.
LIMITATIONS
Small sample sizes, different index episodes and variety of outcome measures.
CONCLUSION
Evidence regarding treatment of rapid cycling remains scarce. Evidence supports the use of aripiprazole, olanzapine, and valproate for acute manic or mixed episodes, quetiapine for acute depressive episodes and aripiprazole and lamotrigine for relapse prevention. Given the paucity of available evidence, and the burden that accompanies rapid cycling, future research is warranted.
Topics: Anticonvulsants; Antipsychotic Agents; Aripiprazole; Bipolar Disorder; Humans; Lamotrigine; Olanzapine; Quetiapine Fumarate; Valproic Acid
PubMed: 35545157
DOI: 10.1016/j.jad.2022.05.017 -
The Cochrane Database of Systematic... Oct 2011Valproic acid and its sodium salt (sodium valproate) are antiepileptic drugs that are sometimes used to treat chronic neuropathic pain and fibromyalgia, although they... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Valproic acid and its sodium salt (sodium valproate) are antiepileptic drugs that are sometimes used to treat chronic neuropathic pain and fibromyalgia, although they are not licensed for this use.
OBJECTIVES
To evaluate the analgesic efficacy and adverse effects of valproic acid and sodium valproate in the management of chronic neuropathic pain and fibromyalgia.
SEARCH STRATEGY
We identified randomised controlled trials (RCTs) of valproic acid and sodium valproate in acute, and chronic pain by searching MEDLINE, EMBASE and Cochrane CENTRAL to June 2011, together with reference lists of retrieved papers and reviews.
SELECTION CRITERIA
RCTs that were double blind and of eight-weeks duration or longer, reporting on analgesic effects and adverse events with valproic acid and sodium valproate in the treatment of chronic neuropathic pain and fibromyalgia.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted results and scored for quality. We extracted efficacy and adverse event data, and examined issues of study quality.
MAIN RESULTS
We included three studies, two in diabetic neuropathy (42 participants treated with valproate, 42 with placebo), and one in post-herpetic neuralgia (23 treated with divalproex sodium, 22 with placebo). Study duration was eight or 12 weeks. No studies were found in fibromyalgia.Only one study reported one of our primary outcomes (≥ 50% pain relief), while all three reported group means for pain reduction from baseline to endpoint. In all three studies; efficacy results were given only for participants who completed the study. One study in diabetic neuropathy and the study in post-herpetic neuralgia reported significant differences between active and placebo groups, but there were insufficient data for reliable pooled analysis.More adverse events were reported with active treatment than placebo, and included nausea, drowsiness and abnormal liver function tests. One participant taking sodium valproate withdrew due to serious derangement of liver enzymes.
AUTHORS' CONCLUSIONS
These three studies no more than hint that sodium valproate may reduce pain in diabetic neuropathy, and divalproex sodium in post-herpetic neuralgia, but the use of 'completer' analysis may overestimate efficacy, and there were too few data for pooled analysis of efficacy or harm, or to have confidence in the results of the individual studies. There is insufficient evidence to support the use of valproic acid or sodium valproate as a first-line treatment for neuropathic pain. There is more robust evidence of greater efficacy for a small number of other drugs.
Topics: Adult; Analgesics; Diabetic Neuropathies; Fibromyalgia; Humans; Neuralgia, Postherpetic; Randomized Controlled Trials as Topic; Valproic Acid
PubMed: 21975791
DOI: 10.1002/14651858.CD009183.pub2 -
Expert Review of Clinical Pharmacology May 2022This study reviewed all published valproic acid (VPA) population pharmacokinetic (PPK) models in adult patients and assessed them using external validation methods to...
Published population pharmacokinetic models of valproic acid in adult patients: a systematic review and external validation in a Chinese sample of inpatients with bipolar disorder.
BACKGROUND
This study reviewed all published valproic acid (VPA) population pharmacokinetic (PPK) models in adult patients and assessed them using external validation methods to determine predictive performance.
METHODS
Thirteen published PPK models (labeled with letters A to M) not restricted to children were identified in PubMed, Embase, and Web of Science databases. They were evaluated in a sample totaling 411 serum concentrations from 146 adult inpatients diagnosed with bipolar disorder in a Chinese hospital. Serum concentrations of VPA were analyzed by validated ultra-performance liquid chromatography-tandem mass spectrometry. Performance was assessed by four tests (prediction-based diagnostics, visual predictive checks, normalized prediction distribution error, and Bayesian forecasting).
RESULTS
Models K and L, developed in large samples of Chinese and Thai patients, showed good performance in our Chinese dataset. Models H and J demonstrated good performance in 2 and 3 of the 4 tests, respectively. Another seven models exhibited intermediate performance. The models with the worst performance, F and M, could not be improved by Bayesian forecasting.
CONCLUSION
In our validation study, the most important factors contributing to good performance were absence of children, Asian ethnicity, one-compartment models, and inclusion of body weight and VPA dose in previously published models.
Topics: Adult; Anticonvulsants; Bayes Theorem; Bipolar Disorder; Child; China; Epilepsy; Humans; Inpatients; Models, Biological; Valproic Acid
PubMed: 35536685
DOI: 10.1080/17512433.2022.2075849